A time-dependent survival analysis for early prognosis of chronic wounds by monitoring wound alkalinity.

The objective is to determine whether monitoring wound alkalinity between visits may help prognosticate chronic wound healing. The alkalinity of 167 wounds during the first 3 visits was assessed using disposable DETEC® pH. Wounds grouped by frequency of alkaline results were compared by % wound size reduction during each visit and 120-day healing probability. The Cox proportional hazards model for time-dependent variables was used to generate non-healing probability curves, where variables are binary (alkaline/non-alkaline, infection/no infection), categorical (wound type), and continuous (wound area); the response is time to complete wound healing; and the event of interest is complete wound healing in 120 days. Results show that wounds with frequent alkaline results have significantly smaller % size reduction per visit. Logistic regression shows an increase in 120-day healing probability with fewer alkaline results. Survival analysis shows that the instantaneous healing rate of non-alkaline or non-alkaline transitioning wounds is 1.785, 2.925, and 5.908 times that of alkaline or alkaline-transitioning wounds for 1, 2, and 3 alkalinity measurements, respectively. Furthermore, the concordance statistic of each survival model shows that goodness of fit increases with more alkalinity measurements. Overall, frequent wound alkalinity assessments may serve as a novel way to prognosticate wound healing outcomes.

A wound alkalinity measurement to predict non-healing wound outcomes.

OBJECTIVE: As wound pH could influence wound healing rates, this study examined the alkalinity of the entire wound during patients' follow-up visits to predict the final non-healing outcome. METHOD: Wound alkalinity of patients with diabetic foot ulcers (DFUs), venous leg ulcers, and other wounds during three follow-up visits within a four week period was recorded. All wounds were followed until 12 weeks to confirm that healed wounds did not relapse. The alkalinity of various wounds over multiple visits with varying durations was compared with final wound status to assess whether one-time wound alkalinity measurement could predict non-healing wounds. The effect of wound types, infection, age and sex on such determinations was also studied. RESULTS: A total of 96 patients were included in this study. Based on probability variations of pre- and post-test non-healing outcomes from multiple visits over 12 weeks, second visit assessment gave the highest increase in risk of non-healing for an alkaline test result (+8.0%) and decrease in risk of non-healing for a non-alkaline test result (-19.7%). Moreover, a second visit (7-21 days from first visit) showed a greater change in risk for non-healing based on alkaline and non-alkaline test results (+15.7% and -38.1% respectively), compared with a visit within seven days (+6.3% and -12.5%, respectively). Wound type, infection, age and sex did not affect the prognostic ability of wound alkalinity. CONCLUSION: The results of this study support that a single wound alkalinity measurement during the second visit (7-21 days from first visit) can be used to predict non-healing wounds. Wound alkalinity may be routinely assessed to predict non-healing wounds and to determine whether the wounds are healing as expected following initial treatment.

A non-contact device for fast screening of wound infections.

Screening for wound infection relies on the expertise of the provider. Clinical diagnosis of infections based on wound swab/biopsy results often takes a few days and may not assess the full wound. There is a need for a non-invasive tool that can quickly and accurately diagnose wound infection. Leukocyte esterase strips are used to identify various infectious diseases. However, it is not clear whether infected wounds also have elevated leukocyte esterase activities as compared with non-infected wounds. To achieve the objective, a device was developed to detect elevated leukocyte esterase activities in wounds by measuring wound exudates adsorbed onto wound dressings in 3 minutes. The efficacy of the device in assessing leukocyte esterase activities across various chronic wounds was tested. Such measurements were unaffected by the type of underlying wound dressing. By correlating the device outputs with clinical adjudication of infection, we found that this device had high positive predictive values for diagnosing wound infection in a wide variety of chronic wounds. In addition, a positive device output increases the probability of detecting infected wounds, while the negative device output reduces the probability of detecting infected wounds. This rapid non-contact and disposable diagnostic tool may serve as a rapid and accurate indication of infection in the chronic wound.

A near-infrared fluorescent pH sensing film for wound milieu pH monitoring.

Studies have shown that wound pH is a potentially influential factor in the healing process. Due to the flaws of traditional pH measurement approaches, wound pH measurement has not become part of current standard of care. A near-infrared pH-sensitive ratiometric film was created and characterized for measuring wound pH. This film was fabricated by physically absorbing poly (N-isopropyl Acrylamide) nanoparticles conjugated with pH-sensitive (CypHer5E) and pH-insensitive (Cy7) fluorescent dyes into 2-hydroxyethyl methacrylate hydrogel film. The pH pattern on wounds can be indirectly measured by pressing freshly discarded wound dressing on top of the pH-sensitive film and imaging it. In vitro tests show that the film can accurately and rapidly detect a wide range of pH (from pH 4 to 8) in wound milieu. Further, patient studies showed that, by measuring pH on wound contact side of discarded wound gauze, the pH and its non-homogeneous distribution on wounds can be indirectly determined. By comparing patients with different wound conditions, we find that near-infrared pH sensing film can be used to measure wound exudate pH with high accuracy and efficiency. In addition, wound pH determination can provide an accurate assessment of wound healing activity in real time.

Diagnostics for Wound Infections.

Significance: Infections can significantly delay the healing process in chronic wounds, placing an enormous economic burden on health care resources. Identification of infection biomarkers and imaging modalities to observe and quantify them has seen progress over the years. Recent Advances: Traditionally, clinicians determine the presence of infection through visual observation of wounds and confirm their diagnosis through wound culture. Many laboratory markers, including C-reactive protein, procalcitonin, presepsin, and bacterial protease activity, have been quantified to assist diagnosis of infection. Moreover, imaging modalities like plain radiography, computed tomography, magnetic resonance imaging, ultrasound imaging, spatial frequency domain imaging, thermography, autofluorescence imaging, and biosensors have emerged for real-time wound infection diagnosis and showed their unique advantages in deeper wound infection diagnosis. Critical Issues: While traditional diagnostic approaches provide valuable information, they are time-consuming and depend on clinicians' experiences. There is a need for noninvasive wound infection diagnostics that are highly specific, rapid, and accurate, and do not require extensive training. Future Directions: While innovative diagnostics utilizing various imaging instrumentation are being developed, new biomarkers have been investigated as potential indicators for wound infection. Products may be developed to either qualitatively or quantitatively measure these biomarkers. This review summarizes and compares all available diagnostics for wound infection, including those currently used in clinics and still under development. This review could serve as a valuable resource for clinicians treating wound infections as well as patients and wound care providers who would like to be informed of the recent developments.

Imaging in Chronic Wound Diagnostics.

Significance: Chronic wounds affect millions of patients worldwide, placing a huge burden on health care resources. Although significant progress has been made in the development of wound treatments, very few advances have been made in wound diagnosis. Recent Advances: Standard imaging methods like computed tomography, single-photon emission computed tomography, magnetic resonance imaging, terahertz imaging, and ultrasound imaging have been widely employed in wound diagnostics. A number of noninvasive optical imaging modalities like optical coherence tomography, near-infrared spectroscopy, laser Doppler imaging, spatial frequency domain imaging, digital camera imaging, and thermal and fluorescence imaging have emerged over the years. Critical Issues: While standard diagnostic wound imaging modalities provide valuable information, they cannot account for dynamic changes in the wound environment. In addition, they lack the capability to predict the healing outcome. Thus, there remains a pressing need for more efficient methods that can not only indicate the current state of the wound but also help determine whether the wound is on track to heal normally. Future Directions: Many imaging probes have been fabricated and shown to provide real-time assessment of tissue microenvironment and inflammatory responses in vivo. These probes have been demonstrated to noninvasively detect various changes in the wound environment, which include tissue pH, reactive oxygen species, fibrin deposition, matrix metalloproteinase production, and macrophage accumulation. This review summarizes the creation of these probes and their potential implications in wound monitoring.

A Device to Predict Short-Term Healing Outcome of Chronic Wounds.

Objective: While myriads of studies have suggested that a survey of wound pH environment could indicate wound healing activities, it is not clear whether wound alkalinity can be used as a prognostic indicator of nonhealing wounds. Currently available systems cannot reliably assess the pH environment across wounds, which is the objective of this study. Approach: A disposable device, DETEC® pH, was developed and characterized on its ability to map wound alkalinity by pressing a freshly recovered wound dressing against its test surface. By comparing the wound's alkalinity and size reduction rates (∼7 days) following pH measurement, we assessed the capability of wound alkalinity to prognosticate subsequent short-term wound size reduction rates. Results: The device had high accuracy and specificity in determining the alkalinity of simulated wound fluids soaked onto wound dressing. The type of wound dressing type had an insignificant effect on its detection sensitivity. Upon testing discarded wound dressings from human patients, the device quickly determined alkaline and acidic wounds. Finally, statistical analyses of wound size reduction rates in wounds with various alkalinities confirmed that wound alkalinity has a strong influence on, at least, short-term wound healing activity. Innovation: Without directly contacting the patient, this device provides a quick assessment of wound alkalinity to prognosticate immediate and short-term wound healing activities. Conclusion: DETEC® pH may serve as a prognosis device for wound care specialists during routine wound assessment to predict wound healing progress. This information can assist the decision-making process in a clinical setting and augur well for chronic wound treatment. DETEC® pH can also be used as an aid for home health care nurses or health care providers to screen nonhealing wounds outside clinics.