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\begin{document}

\title{Successful treatment of a high-risk diabetic foot ulcer by ozone therapy
and collagen powder: a case report}



\author[1]{Hooman Mohammad talebi}%
\author[2]{Javad Javaheri}%
\author[2]{Mohammad Sadegh Fakhari}%
\affil[1]{Isfahan University of Medical Sciences}%
\affil[2]{Arak University of Medical Sciences}%


\vspace{-1em}



  
  \date{June 18, 2024}


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\textbf{Successful treatment of a high-risk diabetic foot ulcer by ozone
therapy and collagen powder: a case report}

\textbf{Running title: Treatment of a high risk diabetic foot ulcer}

Hooman Mohammad talebi (MSN)11Hezar-jarib Street, Isfahan University of
Medical Sciences, Isfahan, Iran., Javad Javaheri 22Alam-al-Hoda Street,
Shahid Shiroodi Street, Arak, Markazi province, Iran(MD), Mohammad
Sadegh Fakhari* (MD)33Alam-al-Hoda Street, Shahid Shiroodi Street, Arak,
Markazi province, Iran, corresponding author

1; faculty of nursing and midwifery, Isfahan university of medical
sciences, Isfahan, Iran

Master of nursing, Wound therapist

0000-0001-5530-0826 nursehooman@yahoo.com

2; Assistant Professor of community medicine, Department of Health and
Community Medicine, Arak University of Medical Sciences

MD, Diabetologist

0000-0002-5342-6094

Javaheri\_115@yahoo.com

3; Student research committee, Arak university of medical sciences,
Arak, Iran

MD

0000-0002-0350-447X fakharisadegh@gmail.com

Conflict of interest:

There was no conflict of interest among authors.

Acknowledgements:

we would like to extend our sincere thanks to Dr. Maryam Jenabi, Dr.
Sahba Sheikholeslami and Dr. Sophia Emamdoost for helping us with
material supports.

Funding:

This study had no funding source

Informed consent

Written informed consent was obtained from the patients to publish this
report in accordance with the journal's patient consent policy.

\textbf{Successful treatment of a high-risk diabetic foot ulcer by ozone
therapy and collagen powder: a case report}

\section*{Abstract}

{\label{abstract}}

This case report presents a successful non-surgical outpatient approach
for managing a high-risk diabetic foot ulcer with tendon exposure in an
older adult with uncontrolled diabetes mellitus and severe heart
failure. Due to the patient's comorbidities, surgical intervention was
not an option, leading to the utilization of ozone therapy, collagen
powder and Phenytoin ointment. The significance of this case lies in the
treatment of a high-risk foot ulcer through a non-surgical approach,
considering the patient's uncontrolled diabetes and severe heart
failure. Diabetic foot ulcers are debilitating and life-threatening
complications, often resulting in amputations, socio-psychological
burdens, and lifestyle changes. Conventional treatment methods have
shown limited success, necessitating the exploration of new and
innovative approaches. The use of ozone therapy has emerged as a
potential treatment, but its safety and efficacy in diabetic foot ulcers
require further investigation. The positive outcomes observed in this
case report suggest that ozone therapy may be a viable option for
treating diabetic foot ulcers, and further studies are recommended to
evaluate its effectiveness.

\section*{Key messages}

{\label{key-messages}}

\begin{itemize}
\tightlist
\item
  A high risk diabetic foot ulcer is treated by ozone therapy and
  collagen powder.
\item
  The goal of this study was to report a high risk case, treated by
  ozone therapy and collagen powder.
\item
  ozone therapy and collagen powder can improve healing process of
  diabetic foot ulcers.
\end{itemize}

\section*{Keywords}

{\label{keywords}}

Diabetic Foot Ulcers, Wound Management, Ozone Therapy

Introduction:

Diabetic foot ulcers (DFUs) cause a significant challenge for diabetic
patients, with a heavy economic and health burden on both the patients
and their family(1). Patients condition become more vulnerable when
there is a risk of amputation and tissue loss. Despite microcirculatory
dysfunctions and neuropathic complications in diabetic patients, older
adult patients are more susceptible to DFU and its consequences due to
degenerative effects of aging(2). surgical interventions such as
secondary flap prostheses or other plastic surgery methods is needed to
treat high-risk DFUs. Indeed, older adults with cardiovascular diseases
or ages above 70 years have limitations to perform surgical methods,
which forces wound therapist and the medical team to choose non-surgical
methods(3).

In this case, we report a high risk tendon exposed DFU healed by ozone
therapy and collagen powder and phenytoin ointment.

Case presentation:

The patient, a 73-year-old Iranian male with uncontrolled diabetes
mellitus, presented with a large diabetic ulcer on his right foot's
Achilles tendon that had been present for three months (figure.1). The
patient had a history of heart failure with an ejection fraction of 30\%
and previously undergone angiography and pacemaker insertion. He had
been self-administering metformin (500 mg, BD) for the past seven years,
and scars on other parts of his foot indicated a history of multiple
healed ulcers.

Upon examination, the patient presented with a Wagner II,
tendon-exposed, non-infected ulcer measuring 10 cm in length and 4.2 cm
in width, with 9.5 cm of Achilles tendon exposed out of the tendon
sheath. The condition had deteriorated due to previous unnecessary
surgical debridement, and the ulcer had only a few granulated tissues in
the wound edges, with most of the ulcer occupied by the tendon.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Fig.1 Day 1; tendon exposed diabetic foot ulcer

The patient was using regular gauzes to dress the ulcer, but the tendon
was at risk of dehydration tensions and necrosis. The patient was
referred to a surgeon for surgical treatment, but due to his
cardiovascular conditions, the medical team decided to perform
non-surgical methods.

In order to manage diabetes; Initial laboratory results indicated a
HbA1C of 9.2\% and mean blood glucose of 226mg/dl. Synoripa 5/500 BD and
daily dose of Gliclazide 30 mg were prescribed. The wound care nurse
provided education on off-loading and diabetic diet tips. By the
10\textsuperscript{th} day, the fasting blood sugar returned to the
normal range. Dressing of the ulcer using silver dressings and hydrogels
commenced, and betaine-polyhexanide solution was used as a proper
disinfectant in every dressing session. After 20 days of every two days
dressing, the healing process seemed to be very slow. Considering the
tendon-exposed, time was extremely vital for the medical team to save
the tendon by granulating the ulcer. Therefore, as the ulcer had a
margin of granulated tissue, 0/5 gram of collagen powder along with
Phenytoin ointment was used each session to boost the granulation
process. Furthermore, as complementary treatment, the patient underwent
ozone therapy by 70 mcg/dl(1). Local ozone therapy was conducted using a
plastic tent on the patient's foot over 24-days period in 12 sessions.
By the day 44, the ulcer was totally granulated, and the Achilles tendon
seemed to be safe (figure.2).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

Fig.2 Granulation phase

In order to manage the exudate and prevent maceration on the pre-wound
skin and wound edge, a foam dressing was applied to the ulcer for
another 20 days (figure.3).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Fig.3 Epithelialization phase

Meanwhile, a new HbA1C and FBS test were performed, and the results
(6.9\% - 104 mg/dI) indicated that the diabetes is under control. By the
day 65, almost all the ulcer was covered by the new immature skin
(figure.4) and the patient returned to his daily activities.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

Fig.4 Day 65; healed ulcer

In order to complete the treatment, the patient and family were educated
by the wound care nurse and physician about dressing with foam dressings
until the new skin matured.

\section*{Discussion}

{\label{discussion}}

In this case report, we present the successful treatment of a high-risk
diabetic foot ulcer in an older adult using ozone therapy and collagen
powder. The patient's comorbidities, including uncontrolled diabetes
mellitus and severe heart failure, precluded surgical management,
necessitating a non-surgical approach in an outpatient setting.

Diabetic foot ulcers are a life-threatening and debilitating
complication of advanced diabetes, often resulting in amputations and
substantial socio-psychological burden for patients. Prevention is a key
component of diabetic foot ulcer management (4). Additionally, managing
underlying diabetes is crucial to prevent further microvascular changes
and decrease the recurrence rate. Conventional treatment methods for
diabetic foot ulcers have had limited success, highlighting the need for
new and innovative approaches (5).

While local muscle flaps are the preferred option for small foot and
ankle ulcers with exposed bone or tendon, non-surgical approaches can
serve as an alternative, especially when patients have comorbidities.
Soft tissue defects involving tendons in the foot and ankle present
challenges in healing due to limited availability of epithelial cells
and lack of soft tissue coverage, further compounded by additional
comorbidities such as severe heart failure (6).

Ozone therapy has emerged as a potential treatment modality in recent
years. Possible mechanisms associated with wound healing in ozone
therapy include antibacterial effects, growth factor release, and tissue
oxygenation (7). However, improper application of ozone therapy can lead
to respiratory tract damage, gastrointestinal symptoms, and headaches
(8).

The use of ozone therapy in diabetic foot ulcers remains controversial,
and its safety and efficacy have not been extensively investigated.
Previous case reports utilizing ozone therapy for diabetic foot ulcer
management have shown positive results, but these studies used different
methods such as ozone bagging (9, 10). In our case, we utilized ozone
therapy by tent.

A study by Kadir et al. showed that ozone therapy as an adjunct to
standard treatment did not significantly impact the healing process but
did reduce bacterial infections (11). Additionally, Uzun et al. reported
a case in which intralesional ozone injection resulted in severe foot
infection and necrosis, suggesting the potential risks of ozone therapy
(12). However, it is important to note that the patient in the Uzun et
al. study had poor adherence to diabetes treatment, which may have
contributed to the negative outcome.

Conclusion:

In conclusion. Critical tendon exposed diabetic foot ulcers can be
healed rapidly by ozone therapy and collagen powder. Consequently,
preventing tendon loss and further complications is more convenient when
the healing process is faster. The authors recommend additional research
in this area to better understand the wound healing process in diabetic
foot ulcers and to determine the optimal use of ozone therapy as a
non-surgical treatment option.

Declarations:

\begin{enumerate}
\tightlist
\item
  Ethical approval and consent to participant A written informed consent
  was obtained from the next of kin. Authors confirm that all methods
  were performed in accordance with institutional ethical standards and
  Declarations of Helsinki.
\item
  Consent for publication A written informed consent for publicly
  reporting the information of the condition was obtained from the
  participant.
\item
  Availability of data and materials All data are available from the
  corresponding author on reasonable request.
\item
  Competing interests All the authors declared no conflict of interest.
\item
  Funding This article was no funded by any individual or organization.
\item
  Authors' contributions Study conception and review of the Literature:
  HMT, MSF, JJ. Clinical management: HMT. Manuscript preparation: HMT,
  MSF. Supervision, Administrative support and critical revision of the
  paper: JJ. All authors read and approved the final manuscript.
\item
  Acknowledgment
\item
  we would like to extend our sincere thanks to Dr. Maryam Jenabi, Dr.
  Sahba Sheikholeslami and Dr. Sophia Emamdoost for helping us with
  material supports.
\end{enumerate}

References

1. Faraji N, Goli R, Choobianzali B, Bahrami S, Sadeghian A, Sepehrnia
N, et al. Ozone therapy as an alternative method for the treatment of
diabetic foot ulcer: a case report. Journal of medical case reports.
2021;15(1):234.

2. Horton WB, Barrett EJ. Microvascular Dysfunction in Diabetes Mellitus
and Cardiometabolic Disease. Endocrine reviews. 2021;42(1):29-55.

3. Smilowitz NR, Berger JS. Perioperative Cardiovascular Risk Assessment
and Management for Noncardiac Surgery: A Review. JAMA.
2020;324(3):279-90.

4. Lim JZM, Ng NSL, Thomas C. Prevention and treatment of diabetic foot
ulcers. Journal of the Royal Society of Medicine. 2017;110(3):104-9.

5. Baltzis D, Eleftheriadou I, Veves A. Pathogenesis and treatment of
impaired wound healing in diabetes mellitus: new insights. Advances in
therapy. 2014;31:817-36.

6. Attinger CE, Ducic I, Cooper P, Zelen CM. The role of intrinsic
muscle flaps of the foot for bone coverage in foot and ankle defects in
diabetic and nondiabetic patients. Plastic and reconstructive surgery.
2002;110(4):1047-54.

7. Teuvov AA, Baziev AM, Lovpache ZN, Teunikova IS, Chudopal SM. Ozone
therapy in the comprehensive treatment of diabetic foot syndrome.
Biomedical and Pharmacology Journal. 2017;10(4):1871-8.

8. Smith NL, Wilson AL, Gandhi J, Vatsia S, Khan SA. Ozone therapy: an
overview of pharmacodynamics, current research, and clinical utility.
Medical gas research. 2017;7(3):212.

9. Dadfar R, Khorsandi L, Goujani R, Mousavi SF, Aslani Z. Therapeutic
utilization of zinc supplementation concurrent with ozone therapy
ameliorates diabetic foot ulcer and attenuates serum level of C-reactive
protein-A case report study. Advanced Biomedical Research. 2023;12.

10. Faraji N, Goli R, Choobianzali B, Bahrami S, Sadeghian A, Sepehrnia
N, et al. Ozone therapy as an alternative method for the treatment of
diabetic foot ulcer: a case report. Journal of medical case reports.
2021;15(1):1-8.

11. Kadir K, Syam Y, Yusuf S, Zainuddin M. Ozone therapy on reduction of
bacterial colonies and acceleration of diabetic foot ulcer healing. Home
Healthcare Now. 2020;38(4):215-20.

12. Uzun G, Mutluo\selectlanguage{polish}ğ\selectlanguage{english}lu M, Karag\selectlanguage{ngerman}öz H, Memi\selectlanguage{polish}ş \selectlanguage{english}A, Karabacak E, Ay H. Pitfalls
of intralesional ozone injection in diabetic foot ulcers: a case study.
Journal of the American College of Clinical Wound Specialists.
2012;4(4):81-3.\selectlanguage{english}
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