Efficacy and safety of Diclofenac sodium plaster in patients with acute pain of the limbs: a randomized, placebo and active-controlled, double-blind, parallel-group trial.

OBJECTIVE: The aim of the present study was to assess the safety and efficacy of Diclofenac sodium (DS) 140 mg medicated plaster vs. Diclofenac epolamine (DIEP) 180 mg medicated plaster and placebo plaster, for the treatment of painful disease due to traumatic events of the limbs. PATIENTS AND METHODS: This was a multicenter, phase III study involving 214 patients, aged 18-65 years, affected by painful conditions due to soft tissue injuries. Patients were randomized to DS, DIEP or placebo arms and treated with once-daily application of the plaster for a total treatment period of 7 days. The primary objective was first to demonstrate the non-inferior efficacy of the DS treatment when compared to the reference DIEP treatment and second that both, test and reference treatments, were superior with respect to placebo. The secondary objectives included the evaluation of efficacy, adhesion, safety, and local tolerability of DS in comparison to both DIEP and placebo. RESULTS: The mean visual analog scale (VAS) score decrease for pain at rest was higher in the DS (-17.65 mm) and the DIEP group (-17.5 mm) than in the placebo (-11.3 mm). Both active formulation plasters were associated with a statistically significant pain reduction compared to placebo. No statistically significant differences were observed between DIEP and DS plasters efficacy in relieving pain. Secondary endpoint evaluations supported the primary efficacy results. No serious adverse events (SAEs) were registered, and the most commonly detected adverse events were skin reactions at the application site. CONCLUSIONS: The results showed that both the DS 140 mg plaster and the reference DIEP 180 mg plaster are effective in relieving pain and present a good safety profile.

Examining relationship between occupational acid exposure and oral health in workplace.

BACKGROUND: Acid mist can suspend in the air and enter the body via skin contact, the respiratory tract, or even oral intake, which pose various health hazards. Previous studies have shown that occupational exposure to acid mist or acidic solutions is a major risk factor for oral diseases. However, the findings are inconsistent and do not consider individual factors and lifestyles that may cause the same oral diseases. Therefore, we conducted a comprehensive oral health survey and collected detail information to confirm the effect of acidic solution exposure on worker's oral health. METHODS: From 4 acidic solution factories, a total of 309 subjects (157 in control and 152 in exposed group) was enrolled. All participants competed oral examinations and self-report questionnaire, including the decayed, missing, and filled teeth (DMFT) index, community periodontal index (CPI), loss of attachment (LA) index, and tooth erosion. Multivariate logistic regression analysis was used to determine the association between the acidic solution exposure and oral health. RESULTS: The results showed that acid exposure was correlated with soft oral tissue injury rather than hard oral tissue in our survey. In the multivariate model (adjusted for sex, age, worked years, education level, mouthwash use, dental floss use, tooth brushing, mask use, smoking, drinking, chewing areca and dietary habits with acidic foods), significant relationships of acid exposure with LA score were observed (OR = 2.32, 95% CI 1.03-5.26). However, the presence of acid exposure was not significantly associated with tooth erosion, DMFT, and CPITN. CONCLUSION: Our study highlighted that occupational acid exposure was an independent risk factor for periodontal health, especially LA. It is important to strengthen occupational hazard control, educate workers on oral disease and related factors, and raise the awareness of oral hygiene.

The Krampus and the Old, Dark Christmas-Full-thickness Contact Alkali Burn With Soot, Milking Grease and Baby Oil.

A chemical alkali burn caused by ash and soot is quite rare, resulting from its high pH-value, and underestimated in its potential to cause injury. In folkloric medicine, ash was purportedly used to relieve pain. We present an unusual case of a 27-year-old man who used a self-mixed cream of soot of wooden pellets, milking grease and baby oil to blacken his face and hands for a traditional Krampus procession.

Significance of antenatal glucocorticoid exposure for pressure injury prevalence in neonates.

AIMS: Studies have highlighted that antenatal steroids could have an effect on neonatal skin maturation. This study examined if there was a relationship between the administration of antenatal glucocorticoids for mothers and the skin injuries in their neonates. Data from skin injury audit were extracted from the neonatal database and analyzed to determine differences in the prevalence of neonates with pressure injuries [cases] whose mothers had received antenatal steroids, compared to those without pressure injuries [control]. RESULTS: Of 247 neonates audited, 77 [31%], had documented pressure injuries, 170 [69%] had no documented injury. The median birth weight and gestation were 1400 g [IQR 893-2268 g] and 30.3 weeks [IQR 26.3-40.0 weeks] respectively. Of the neonates born less than 34 weeks, 80% were exposed to antenatal steroids and were equally distributed across patient genders. Within the 77 cases, 53 [66%] were exposed to antenatal steroids compared to controls in which 88 [53%] had not. The effect between cases and controls was not statistically significant [χ2 = 2.81, P = 0.09]. However a difference was noted between genders, as female neonates benefited from the exposure to steroids [OR = 0.317, 95% [CI 0.105-0.956], p value -0.041]. CONCLUSION: Antenatal glucocorticoids appear to be beneficial in reducing pressure injury prevalence in female neonates.

Genetic alterations in periprosthetic soft-tissue masses from patients with metal-on-metal hip replacement.

Adverse soft tissue reactions in patients with metal-on-metal (MoM) hip replacement are associated with cobalt (Co) and chromium (Cr) particles released from the implant. Exposing the patients to long periods of increased metal ions concentrations resulting from the wear of these implants poses an increased risk of genotoxicity/mutagenicity. A variable proportion of patients develop periprosthetic soft-tissue masses or pseudotumors at the site of the implant. There is a concern that exposure to increased metal ions could increase the risk of cancer. In order to investigate whether the periprosthetic soft-tissue mass harbours any cancer- related genetic alterations, we studied DNA isolated from periprosthetic tissues of 20 patients with MoM hip replacement, for copy number alterations and mutations in hotspot regions of 50 cancer genes using aCGH and amplicon-based next generation sequencing. Our results showed copy number gains at 12q14.3 and 21q21.1in tumour from patient diagnosed with liposarcoma. Copy number alterations in periprosthetic tissues were seen in three other patients, one had a region of gain at 9q24.1 affecting JAK2 and INSL6, and two patients had region of gain at 6p21.1, affecting RUNX2. Mutation analysis showed V1578del mutation in NOTCH1 in two patients. The copy number alterations and mutations seen in periprosthetic soft-tissue masses are earlier reported in either haematological malignancies or in osteoblast related bone dysplasia. The presence of genetic anomalies was associated with longer in-situ time of the implant. Our findings warrant the need of similar studies in larger patient cohorts to evaluate the risk of development of neoplastic alterations in periprosthetic tissues of patients with MoM hip replacement.

Subcutaneous Injection of Percocet: A Case of Severe Soft Tissue Loss.

Prescription drug abuse ranks as the second most common class of illicit drug use in the United States, and one mechanism of opiate abuse involves intravenous injection of enteral narcotics such as oxycodone or hydrocodone. The authors describe a patient who sustained significant soft tissue necrosis after intravenously injecting a solution made from crushed enteral narcotics, with a focus on the operative course that resulted due to a delay in initial definitive treatment. The patient's wounds encompassed 8% total body surface area and covered 247 cm2. A 55-year-old female was admitted to the burn unit (West Penn Burn Center, Western Pennsylvania Hospital, Pittsburgh, PA) after she initially presented with infection and cellulitis to her bilateral upper extremities 3 weeks after intravenously injecting herself with crushed oxycodone/acetaminophen. She underwent numerous sequential operative repairs including initial debridement, placement of dermal replacement templates, and several split-thickness autografts and xenografts. Her total length of stay was 59 days, broken into an initial 47-day stay, and a subsequent 12-day readmission due to graft failure secondary to poor follow-up. As the number of prescription drug abusers rises, it is possible that an increase in attempts to intravenously abuse enteral narcotics may also rise. As such, burn centers should be prepared for the extent of potential limb necrosis and the operative treatment that may ensue.

Eighteen cases of soft tissue atrophy after intralesional bleomycin a5 injections for the treatment of infantile hemangiomas: a long-term follow-up.

Pingyangmycin is a commonly used drug in China for the treatment of infantile hemangiomas (IHs) and vascular malformations. Also known as bleomycin A5, it has a similar chemical structure to bleomycin. The side effects of bleomycin include swelling, erythema, fever, headache, hyperpigmentation, ulceration, allergic reactions, and pulmonary fibrosis. We conducted this retrospective study to identify the correlation between bleomycin A5 injections and soft tissue atrophy. We performed a retrospective chart review of all patients with IHs who had this treatment and presented with soft tissue atrophy in our department from January 2011 through July 2013. Eighteen children with IHs (14 girls, 4 boys) were included in this study. The average age was 8.6 ± 3.8 years. All of the atrophied deformities were located at the injection site. Thirteen (72.2%) were located on the upper lip, three (16.7%) on the nose, and two (11.1%) on the cheeks. Seventeen (94.5%) received their first injection at the age of 1 or 2 months. The mean number of injections was 3.5 ± 1.6. The mean interval between injections was 1.2 ± 0.3 months. Eight of 18 patients (44.4%) had ulceration after injection. Intralesional bleomycin A5 injection is not safe for the treatment of IHs because it may lead to soft tissue atrophy. Other safer treatments, such as oral propranolol, should replace this treatment.

A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters.

PURPOSE: The aim of this study was to collect and describe all published reports of local tissue injury or extravasation from vasopressor administration via either peripheral intravenous (IV) or central venous catheter. METHODS: A systematic search of Medline, Embase, and Cochrane databases was performed from inception through January 2014 for reports of adults who received vasopressor intravenously via peripheral IV or central venous catheter for a therapeutic purpose. We included primary studies or case reports of vasopressor administration that resulted in local tissue injury or extravasation of vasopressor solution. RESULTS: Eighty-five articles with 270 patients met all inclusion criteria. A total of 325 separate local tissue injury and extravasation events were identified, with 318 events resulting from peripheral vasopressor administration and 7 events resulting from central administration. There were 204 local tissue injury events from peripheral administration of vasopressors, with an average duration of infusion of 55.9 hours (±68.1), median time of 24 hours, and range of 0.08 to 528 hours. In most of these events (174/204, 85.3%), the infusion site was located distal to the antecubital or popliteal fossae. CONCLUSIONS: Published data on tissue injury or extravasation from vasopressor administration via peripheral IVs are derived mainly from case reports. Further study is warranted to clarify the safety of vasopressor administration via peripheral IVs.

A prospective cohort study on the impact of smoking on soft tissue alterations around single implants.

OBJECTIVES: To compare smokers to non-smokers in terms of soft tissue alterations following single implant treatment in healed bone. MATERIAL AND METHODS: Non-smoking and smoking patients with sufficient bone volume in need of a single implant in the anterior maxilla (15-25) were consecutively recruited in three centres. Conventional single implant surgery was performed and an immediate provisional crown was installed. Eight to 12 weeks later, the latter was replaced by a permanent one (baseline). Papilla regrowth and midfacial recession was registered after 2 years of function. RESULTS: The sample consisted of 39 non-smokers (21 females; mean age 42) and 46 smokers (22 females; mean age 45). Smokers had three early failures, whereas all implants integrated successfully in non-smokers. Statistically significant papilla regrowth was observed in non-smokers (distal 0.63 mm, mesial 0.76 mm), whereas smokers showed stable papillae (between cohorts: P ≤ 0.025). Midfacial soft tissue level demonstrated statistically significant regrowth in non-smokers (0.53 mm), whereas it remained stable in smokers (between cohorts: P = 0.004). CONCLUSION: Smokers failed to demonstrate papilla regeneration and showed more midfacial recession following single implant treatment when compared to non-smokers.

BMP-2 adverse reactions treated with human dose equivalent dexamethasone in a rodent model of soft-tissue inflammation.

STUDY DESIGN: Basic science rodent model of bone morphogenetic protein-2 (BMP-2) soft-tissue inflammation. OBJECTIVE: This study investigated the anti-inflammatory effect of human dose equivalent (HDE) dexamethasone (DM) for treatment of BMP-2-related soft-tissue inflammation in a rodent model and suggests an appropriate dose for utilization in the clinical practice of spine surgeons. SUMMARY OF BACKGROUND DATA: BMP-2 is frequently used in spinal surgery to augment fusion. Yet, side effects of soft-tissue inflammation have been observed. DM decreases proinflammatory cytokine production and cellular immune response. However, the anti-inflammatory effects of HDE DM in a rodent model of BMP-2-associated soft-tissue inflammation have not been reported. METHODS: Five, 10, and 15 mg of HDE DM were administered 3 times perioperatively to rodent cohorts receiving BMP-2 paraspinal implants and compared against BMP-2 only positive controls and phosphate buffer negative controls (n = 6 subjects per group). Histopathology, magnetic resonance imaging, and gross dissection were used as measures of cellular, edematous, and exudative inflammatory response. Serial killings were made on day 2 and day 7 postoperatively. RESULTS: Magnetic resonance imaging volume rendering demonstrated inflammatory edema decreased by 49% from 605.4 mm to 304.03 mm in subjects treated with 5, 10, or 15 mg of HDE DM (P < 0.05). Histopathological analysis demonstrated inflammatory cross-sectional area decreased 28.8% from 1.84 mm to 1.31 mm in subjects treated with 5, 10 or 15 mg of HDE DM (P < 0.05). Immune cellular infiltration depth decreased 38.5% from 0.26 mm to 0.16 in subjects treated with 15 mg of HDE DM (P < 0.05). Gross anatomical inflammatory exudates were prevented in 100% of subjects treated with 10 or 15 mg of HDE DM (P < 0.05). CONCLUSION: Low-dose DM administration is effective in controlling the cellular inflammation and edema resulting from BMP-2. Ten or 15 mg of DM might be considered by spine surgeons for controlling the inflammation and edema seen in spine surgery with BMP-2.

Age dependent increase in the levels of osteopontin inhibits skeletal muscle regeneration.

Skeletal muscle regeneration following injury is accompanied by rapid infiltration of macrophages, which play a positive role in muscle repair. Increased chronic inflammation inhibits the regeneration of dystrophic muscle, but the properties of inflammatory cells are not well understood in the context of normal muscle aging. This work uncovers pronounced age-specific changes in the expression of osteopontin (OPN) in CD11b+ macrophages present in the injured old muscle as well as in the blood serum of old injured mice and in the basement membrane surrounding old injured muscle fibers. Furthermore, young CD11b+ macrophages enhance regenerative capacity of old muscle stem cells even when old myofibers and old sera are present; and neutralization of OPN similarly rejuvenates the myogenic responses of old satellite cells in vitro and notably, in vivo. This study highlights potential mechanisms by which age related inflammatory responses become counter-productive for muscle regeneration and suggests new strategies for enhancing muscle repair in the old.

Once initiated, how does toxic tissue injury expand?

Once initiated, how tissue injury expands after high toxicant doses, even after their complete elimination, is not understood. Free-radical generation was initially proposed to mediate progression of injury. However, mechanisms proposed thus far have remained unsubstantiated. Necrotic injury is characterized by loss of osmoregulation, cell swelling, blebbing, and cell rupture. This exposes cytosolic enzymes, including proteases, phospholipases, and lysosomal Ca(2+)-dependent enzymes, to high extracellular calcium (Ca(2+)). Activated hydrolytic enzymes, termed 'death proteins,' hydrolyze their substrates in the plasma membrane of neighboring cells, commencing self-perpetuated injury progression. Likewise, ischemia-reperfusion injury exposes the hydrolytic enzymes to high Ca(2+), fuelling the progression of tissue injury. This mechanism is independent of the offending toxicant that initiates the injury. I present here a case for therapeutic intervention with inhibitors directed against death proteins as a means to avert organ failure and death well after the poisoning event.

Levamisole-induced necrosis of skin, soft tissue, and bone: case report and review of literature.

This represents the largest case of skin necrosis related to levamisole, a common cocaine contaminant, requiring closure with skin grafts, and is the only case resulting in nasal amputation, central upper lip excision, extremity bone necrosis, and above knee amputation. The case report is followed by a review of the literature. Unique considerations for the full-thickness necrosis induced by levamisole vasculitis are highlighted, including antibody level monitoring, need for multiple excisions, timing of skin grafting, and potential for soft tissue and bone necrosis as well. A 54-year-old man presented to an outside facility with fever, generalized weakness, and agranulocytosis, with a history of cocaine use 3 weeks before. After admission, he developed generalized violaceous lesions and an elevated p-antineutrophilic cytoplasmic antibody and was diagnosed with disseminated vasculitis and agranulocytosis secondary to levamisole-contaminated cocaine exposure. On transfer to the authors' facility, 52% TBSA was involved with violaceous, nonblanching lesions, which progressed to full-thickness necrosis. Local wound care continued until necrotic areas fully demarcated and progressive necrosis stabilized, and skin grafting for closure was not performed until antibody levels normalized. Current treatment of levamisole-induced skin rash or necrosis focuses on discontinuation of levamisole. As demonstrated by this case, extensive necrosis secondary to levamisole-induced vasculitis can be successfully treated with multiple excisions until necrosis stabilizes, and then, split-thickness autografts may be applied. In areas with poor vascular supply or areas with poor functional prognosis, amputation may ultimately be required.

Lower limb salvage in a 7-month-old infant using free tissue transfer.

Free flap reconstruction in infants is extremely rare. A seven-and-a-half-month-old male infant sustained an extensive soft tissue defect on his left knee caused by extravasation of an intraosseous arterenol infusion. A free latissimus dorsi flap was successfully performed for soft tissue reconstruction. Indications, advantages, and outcome of the procedure are discussed.