Effect of a Novel Macrophage-Regulating Drug on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial.

Importance: Delayed healing of diabetic foot ulcers (DFUs) is known to be caused by dysregulated M1/M2-type macrophages, and restoring the balance between these macrophage types plays a critical role in healing. However, drugs used to regulate M1/M2 macrophages have not yet been studied in large randomized clinical trials. Objective: To compare the topical application of ON101 cream with use of an absorbent dressing (Hydrofiber; ConvaTec Ltd) when treating DFUs. Design, Setting, and Participants: This multicenter, evaluator-blinded, phase 3 randomized clinical trial was performed in 21 clinical and medical centers across the US, China, and Taiwan from November 23, 2012, to May 11, 2020. Eligible patients with debrided DFUs of 1 to 25 cm2 present for at least 4 weeks and with Wagner grade 1 or 2 were randomized 1:1 to receive ON101 or control absorbent dressings. Interventions: Twice-daily applications of ON101 or a absorbent dressing changed once daily or 2 to 3 times a week for 16 weeks, with a 12-week follow-up. Main Outcomes and Measures: The primary outcome was the incidence of complete healing, defined as complete re-epithelialization at 2 consecutive visits during the treatment period assessed on the full-analysis set (FAS) of all participants with postrandomization data collected. Safety outcomes included assessment of the incidences of adverse events, clinical laboratory values, and vital signs. Results: In the FAS, 236 eligible patients (175 men [74.2%]; mean [SD] age, 57.0 [10.9] years; mean [SD] glycated hemoglobin level, 8.1% [1.6%]) with DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 4.8 [4.4] cm2) were randomized to receive either the ON101 cream (n = 122) or the absorbent dressing (n = 114) for as long as 16 weeks. The incidence of complete healing in the FAS included 74 patients (60.7%) in the ON101 group and 40 (35.1%) in the comparator group during the 16-week treatment period (difference, 25.6 percentage points; odds ratio, 2.84; 95% CI, 1.66-4.84; P < .001). A total of 7 (5.7%) treatment-emergent adverse events occurred in the ON101 group vs 5 (4.4%) in the comparator group. No treatment-related serious adverse events occurred in the ON101 group vs 1 (0.9%) in the comparator group. Conclusions and Relevance: In this multicenter randomized clinical trial, ON101 exhibited better healing efficacy than absorbent dressing alone in the treatment of DFUs and showed consistent efficacy among all patients, including those with DFU-related risk factors (glycated hemoglobin level, ≥9%; ulcer area, >5 cm2; and DFU duration, ≥6 months). Trial Registration: ClinicalTrials.gov Identifier: NCT01898923.

Dried salted plum consumption ameliorates hyperbaric oxygen therapy-induced otalgia severity at the first chamber session: a prospective randomized controlled study.

PURPOSE: One of the most common complications of hyperbaric oxygen (HBO2) therapy is middle ear barotrauma (MEB), occasionally causing otalgia. The objective of this study was to evaluate the effect of dried salted plum consumption on MEB and otalgia associated with HBO2 therapy. MATERIALS AND METHODS: Patients undergoing the first chamber session of HBO2 therapy were included in the present prospective randomized controlled trial. The Valsalva maneuver was administered to all patients before HBO2. The patients were randomly divided into two groups: one that ate a dried salted plum during HBO2 treatment and the other that did not. An otoscopic examination was performed after HBO2 therapy. The MEB was graded according to Teed scores. The degree of otalgia was recorded using the Visual Analog Scale (VAS). RESULTS: Ninety patients were enrolled. The overall incidence of MEB (Teed score grade 1~4) was 39.6% (21 of 53) for patients administered a dried salted plum versus 37.8% (14 of 37) for the control group (P=1.000). The incidence of mild MEB (Teed score grade 1~2) and severe MEB (Teed score Grade 3~4) between the two groups was not significantly different. Otalgia was present in 5.7% (3 of 53) of patients administered a dried salted plum versus 18.9% (7 of 37) for the control group (P=.085). No patients administered a dried salted plum had a VAS score ≥4 for otalgia versus 10.8% (4 of 37) for the control group (P=.026). CONCLUSIONS: Dried salted plum consumption does not decrease the incidence of MEB, but may ameliorate the severity of first chamber session HBO2-induced otalgia.

Management of necrotising fasciitis secondary to abdominal liposuction using a combination of surgery, hyperbaric oxygen and negative pressure wound therapy in a patient with burn scars.

Liposuction is the one of the most frequently performed cosmetic operations and usually has an easy recovery, with a reportedly low overall complication rate. Here, we report the case of a 60-year-old woman with type II diabetes mellitus and a previous burn injury of the abdomen who underwent abdominal liposuction and subsequently developed necrotising fasciitis. Following radical debridement, systemic antibiotic administration, negative pressure wound therapy and hyperbaric oxygen therapy, the wound healed completely. This case demonstrates the success of the combination treatment and highlights the need for clinicians to be aware of the risk of serious complications in selected patients.

Is hyperbaric oxygen therapy indispensable for saving mutilated hand injuries?

Mutilated hand injuries are a profound challenge to the plastic surgeon, and such injuries often lead to limb loss and severe functional impairment. Hyperbaric oxygen therapy (HBOT) appears to counteract tissue hypoxia and stimulate acute wound healing. This study was performed to evaluate the efficacy of HBOT as an adjunctive therapy in patients with a mutilated hand injury. Between January 2006 and December 2014, 45 patients with a mutilated hand injury were enrolled. After reconstruction or revascularisation, patients underwent 120 minutes of HBOT with oxygen at 2·5 atmospheres absolute while breathing 100% oxygen. Outcomes such as amputee survival and surgery-related complications were recorded. The patients were 38 men and 7 women with average age of 37·2 years (range 18-62). The mean defect area was 131·5 cm2 (range 40-300). Most patients experienced a pure crush injury (53%). The average number of operations from the initial debridement to the first reconstruction was 3·8 (range 1-6). A total of 33 patients (73%) underwent replantation during the initial reconstruction. For flap coverage, most patients received a free flap using an anterolateral thigh flap (18 patients) or local flap using an abdomen/groin flap (nine patients). The average time from the first reconstruction or revascularisation to the first HBOT was 6·5 hours (range 2-12). The average number of HBOT sessions was 9·1 (range 6-14 sessions). The survival rate of the replanted fingers was 81%, and the survival rate of the palms was 100%. Most complications in the initial reconstruction involved partial loss of an avulsed flap, and most complications in the chronic stage (≥3 months) involved scar contracture. When combined with delicate microsurgery, early intervention using adjunctive HBOT was effective in preserving partially viable tissue and restoring hand function in patients with a mutilated hand injury.

Hyperbaric Oxygen Therapy for the Adjunctive Treatment of Pyoderma Gangrenosum: A Case Report.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown etiology characterized by an ulcerative skin condition and confirmed through a diagnosis of exclusion. Management usually consists of systemic drug therapy, such as corticosteroids, sulfones, or immunosuppressants, either alone or in combination. Long-term use of these medications often has untold side effects. Hyperbaric oxygen therapy (HBOT) has been shown effective in the treatment of PG, reducing pain and tempering the need for medication. A case is presented of a 54-year-old woman with diabetes, hypertension, and a peptic ulcer who presented with painful, purulent ulcers on her buttocks, hands, and lower extremities of 2 weeks' duration. She was ultimately diagnosed with PG and provided 20 mg/day of oral prednisone for 1 week, tapered to 10 mg/day in the next week and then stopped. In addition, she received 12 sessions of HBOT - she breathed in 100% oxygen under 2.5 atmospheres absolute pressure for 90 minutes over 2 weeks. Her wounds healed without scarring. This excellent outcome including good wound healing, decreased pain, and reduced doses of systemic corticosteroids warrants additional study of the adjunctive use of HBOT for PG.

Histochemical and functional improvement of adipose-derived stem cell-based tissue-engineered cartilage by hyperbaric oxygen/air treatment in a rabbit articular defect model.

Cartilage is exposed to compression forces during joint loading. Therefore, exogenous stimuli are frequently used in cartilage tissue engineering strategies to enhance chondrocyte differentiation and extracellular matrix (ECM) secretion. In this study, human adipose-derived stem cells were seeded on a gelatin/polycaprolactone scaffold to evaluate the histochemical and functional improvement of tissue-engineered cartilage after hyperbaric oxygen/air treatment in a rabbit articular defect model. Behavior tests showed beneficial effects on weight-bearing and rear leg-supporting capacities after treatment of tissue-engineered cartilage with 2.5 ATA oxygen or air. Moreover, positron emission tomography images and immunohistochemistry staining demonstrated hydroxyapatite formation and increased ECM synthesis, respectively, at the tissue-engineered cartilage graft site after high pressure oxygen/air treatment. Based on these results, we concluded that hyperbaric oxygen and air treatment can improve the quality of tissue-engineered cartilage in vivo by increasing the synthesis of ECM.

Predicting duration of mechanical ventilation in patients with carbon monoxide poisoning: a retrospective study.

PURPOSE: Patients with severe carbon monoxide (CO) poisoning may develop acute respiratory failure, which needs endotracheal intubation and mechanical ventilation (MV). The objective of this study was to identify the predictors for duration of MV in patients with severe CO poisoning and acute respiratory failure. MATERIALS AND METHODS: This is a retrospective observational study of 796 consecutive patients diagnosed with acute CO poisoning that presented to the emergency department. Patients who received MV were divided into 2 groups: the early extubation (EE) consisting of patients who were on MV for less than 72 hours and the nonearly extubation (NEE) consisting of patients who were on MV for more than 72 hours. Demographic and clinical data of the two groups were extracted for analysis. RESULTS: The intubation rate of all CO-poisoned patients was 23.4%. A total of 168 patients were enrolled in this study. The main source of CO exposure was intentional CO poisoning by charcoal burning (137 patients). Positive toxicology screening result was found in 104 patients (61.9%). The EE group had 105 patients (62.5%). On arriving at the emergency department, high incidence of hypotension; high white blood cell count; and elevation of blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, creatine kinase, and troponin-I levels were statistically significant in the NEE group (P < .05). Positive toxicology screening result was statistically significant in the EE group (P < .05). In a multivariate analysis, elevation of troponin-I level was an independent factor for NEE (odds ratio, 1.305; 95% confidence interval, 1.024-1.663; P = .032). Positive toxicology screening result was an independent factor for EE (odds ratio, 0.222; 95% confidence interval, 0.101-0.489; P = .001). CONCLUSIONS: A positive toxin screen predicts extubation within the first 72 hours for patients with severe CO poisoning and acute respiratory failure. On the other hand, elevation of initial troponin-I level is a predictor for a longer duration of MV.

The effect of hyperbaric oxygen and air on cartilage tissue engineering.

There is an urgent need to develop tissue-engineered cartilage for patients experiencing joint malfunction due to insufficient self-repairing capacity of articular cartilage. The aim of this research was to explore the effect of hyperbaric oxygen and air on tissue-engineered cartilage formation from human adipose-derived stem cells seeding on the gelatin/polycaprolactone biocomposites. The results of histological analyses indicate that under hyperbaric oxygen and air stimulation, the cell number of chondrocytes in cartilage matrix was not significantly increased, but the 1,9-dimethylmethylene blue assay showed that the glycosaminoglycans syntheses markedly increased compared to the control group. In quantification real-time polymerase chain reaction results, the chondrogenic-specific gene expression of SOX9, aggrecan, and COL2A1 were compared respectively. Within the limitation of this study, it was concluded that 2.5 atmosphere absolute oxygen and air may provide a stress environment to help cartilage tissue engineering development.