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درمان دیابت با سلول بنیادی

Stem Cell Therapy Could Be Breakthrough Against Type 1 Diabetes

WEDNESDAY, Oct. 4, 2023 — People with type 1 diabetes lack functional islet cells in their pancreas to produce the hormone insulin and must take daily insulin via injections or a continuous pump to compensate.

Stem Cells and the Search For a Type 1 Diabetes Cure

But if new research pans out, some folks with type 1 diabetes may no longer need to take insulin. The study of six people with type 1 diabetes found that an investigational off-the-shelf form of islet stem cell therapy improves blood sugar control and slashes insulin needs, with three people no longer needing any daily insulin.

Given via an infusion, VX-880 are stem cell-derived, insulin-producing islet cells that essentially replace the dysfunctional islet cells in people with type 1 diabetes. The study was funded by VX-880 maker Vertex Pharmaceuticals.

“Islet cells have the potential to cure diabetes, and I believe this study is a huge step forward in that direction,” said study author Dr. Trevor Reichman, surgical director of the Pancreas and Islet Transplant Program at University Health Network’s Ajmera Transplant Center in Toronto, Canada.

Type 1 diabetes occurs when the pancreas produces little to no insulin. Insulin is needed to help blood sugar, or glucose, enter the cells, where it is used for energy. When insulin is in short supply, glucose can build up, causing such symptoms as extreme fatigue, blurry vision, weight loss and confusion.

Stem cells can multiply exponentially and morph into different types of cells. The cells used in VX-880 are grown in a lab. Once implanted, they morph into islet cells and can produce insulin.

“They are essentially off-the-shelf but do take several weeks to produce prior to infusion,” Reichman said.

In the new study, all six people treated with VX-880 had improved glycemic control, as shown by elimination of severe low blood sugar reactions, improved HbA1c (a snapshot of blood sugar levels over time), and the amount of time their blood sugar levels were in the recommended range within three months.

As a result, these patients needed less insulin or none at all.

“The impact … was truly life-changing,” Reichman said. “All of these patients had long-standing, difficult-to-manage type 1 diabetes with life-threatening complications, which included severe hypoglycemic unawareness.” Hypoglycemia unawareness means a person can’t tell when their blood glucose gets low, so they don’t know they need to treat it.

Within three months, this was eliminated in all study participants.

Exactly how long these effects will last is not yet known.

“The longest patient in follow-up is now at two years and maintains insulin independence,” Reichman said. The research is ongoing.

The study showed VX-880 is safe, and no serious side effects were reported.

People do need to take immunosuppressant drugs to prevent rejection, which Reichman called a potential roadblock for broader use.

“The future goal is to create a version of the treatment that does not require immunosuppressive therapy,” he said.

The study is limited to people aged 18 through 65 years of age, but in the future, kids may be included.

The findings were presented Tuesday at a meeting of the European Association for the Study of Diabetes, in Hamburg, Germany. Findings presented at medical meetings should be considered preliminary until they are published in a peer-reviewed journal.

Dr. John Buse is the director of the Diabetes Care Center at the University of North Carolina, Chapel Hill.

“The important thing here is that people do not need organ donors to have a source of insulin-producing cells for transplant,” said Buse, who reviewed the findings.

The new stem cell treatment seems to work “pretty well,” he added.

“The patients have to take immunosuppression but they had severe hypoglycemia beforehand so that is a reasonable trade-off for having to take insulin,” Buse said.

Sources

  • Trevor Reichman, MD, surgical director, Pancreas and Islet Transplant Program, University Health Network&rsquo
  • s Ajmera Transplant Center, Toronto, Ontario, Canada
  • John Buse, MD, PhD, director, University of North Carolina Diabetes Care Center, Chapel Hill, N.C.
  • presentation, European Association for the Study of Diabetes meeting, Hamburg, Germany, Oct. 3, 2023
زخم سوختگی

Introduction and treatment of burn wounds

There are many types of burn wounds caused by thermal, radiation, chemical, or electrical contact.

  • Thermal burnsThese burns are due to heat sources which raise the temperature of the skin and tissues and cause tissue cell death or charring. Hot metals, scalding liquids, steam, and flames, when coming into contact with the skin, can cause thermal burns.

 

  • Radiation burns. These burns are due to prolonged exposure to ultraviolet rays of the sun, or to other sources of radiation such as X-ray.

 

  • Chemical burns. These burns are due to strong acids, alkalies, detergents, or solvents coming into contact with the skin or eyes.

 

  • Electrical burns. These burns are from electrical current, either alternating current (AC) or direct current (DC).

 

What are the classifications of burns?

Burns are classified as first-, second-, or third-degree, depending on how deep and severely they penetrate the skin’s surface.

  • First-degree (superficial) burns
    First-degree burns affect only the epidermis, or outer layer of skin. The burn site is red, painful, dry, and with no blisters. Mild sunburn is an example. Long-term tissue damage is rare and usually involves an increase or decrease in the skin color.

 

  • Second-degree (partial thickness) burns
    Second-degree burns involve the epidermis and part of the dermis layer of skin. The burn site appears red, blistered, and may be swollen and painful.

 

  • Third-degree (full thickness) burns
    Third-degree burns destroy the epidermis and dermis. Third-degree burns may also damage the underlying bones, muscles, and tendons. When bones, muscles, or tendons are also burned, this may be referred to as a fourth-degree burn. The burn site appears white or charred. There is no feeling in the area since the nerve endings are destroyed.

 

wound vacuum therapy in burn wound

Third degree burns, after adequate debridement, may benefit from NPT, which may be applied as an adjuvant in bed preparation for subsequent skin grafting, or as a method of optimizing the integration of skin grafts. Patients with electrical trauma, which generally cause deep burn wounds with extensive tissue destruction and progressive tissue damage, are also NPT candidates. The increase in blood perfusion secondary to NPT use is beneficial to burn injury. Kamolz et al. observed this in 2003, in a prospective study comparing the blood perfusion of burned hands that underwent conservative therapy and NPT. In the conservatively treated group, the authors observed reduced limb blood perfusion, which did not occur in the NPT-treated group.

زخم تروماتیک

wound vacuum therapy in traumatic wounds

Traumatic wounds include a group of acute, generally extensive, wounds with loss of cutaneous lining, associated or not with fractures. They are represented by degloving wounds, exposed fractures, wounds associated with muscular crushing, and others, affecting predominantly patients of economically active age.

The stimulation to the formation of granulation tissue in these wounds may be responsible for the reduction in the complexity of the reconstruction option. For example, NPT can promote the coverage of exposed bones and tendons by granulation tissue, allowing wound closure by means of skin grafting, rendering unnecessary the use flaps, with and without concomitant use dermal matrices.

In 2012, Blum et al. evaluated the effect of NPT on the rate of infection in 220 patients with exposed tibial fractures, through a multicenter retrospective cohort study. The infection rate of the NTP group was lower (8.4% x 20.6%, p=0.01) compared with the group receiving conventional moist dressing. In 2006, Yang et al. evaluated the efficacy of NPT in the Treatment of 34 patients with fasciotomy wounds after traumatic compartment syndrome. The mean time to final wound closure was 6.7 days for the NPT group and 16.1 days for the conventional moist dressing group (p<0.05).

In 2013, Milcheski et al. studied 178 patients with traumatic lower limb wounds, most of them represented by degloving wounds. NPT significantly reduced the morbidity and healing time when compared with the previously used conventional dressings. According to the authors, NPT is useful in the treatment of acute traumatic wounds, acting as a bridge between emergency treatment and definitive cutaneous coverage.

زخم فشاری

Negative pressure therapy for the pressure ulcers

Pressure ulcers (PU) are caused by the pressure maintained between a bone prominence and the patient’s bed, leading to ischemia and necrosis of the involved tissues. They are common in patients with some mobility restriction, such as spinal cord injuries (paraplegic and quadriplegic) and patients under prolonged sedation. The most frequent sites of their development are the sacral, sciatic, trochanteric, calcaneal and occipital regions, among others.

The application of wound vacuum therapy in these wounds has the main objective of improving the local conditions for a later repairing surgery to obtain definitive cutaneous cover. This sequence is valid mainly in the cases of Pressure ulcers stages III and IV of the National Pressure Ulcer Advisory Panel (NPUAP), represented by deeper wounds, with muscular or bone exposure. Clinical reports such as that performed by Batra and Asseja19, however, show that even more complex wounds, when acute, could be treated only with NPT.

In 2002, Ford et al conducted a randomized, controlled study with 41 patients with deep Pressure ulcers, comparing NPT with topical healing promoter gels. The mean percentage reduction in ulcer volume was higher in the NPT group (51.8% vs. 42.1%, p=0.46). The mean number of capillaries per wound bed field was also higher in the NPT group (p=0.75). The authors stated that NPT promotes healing and neovascularization when compared to topical gel treatment20.

Ashby et al., in 2012, conducted a randomized controlled trial in patients with pressure ulcers grades III and IV, showing superior benefits of NTP in comparison with moist dressing.

source: https://www.scielo.br/j/rcbc/a/W6qy4BFN9DkdTRsGy6jrfkk/?lang=en&format=html#

skin equivalent

Printing technique creates effective skin equivalent, heals wounds

Chronic wounds are deep and difficult to repair. Often, the top of the injury heals before the bottom, so the wound collapses in on itself. Over time, this can result in scar tissue and reduced skin function. Skin equivalent is a new way for healing wounds.

In APL Bioengineering, by AIP Publishing, researchers from the University of Birmingham and University of Huddersfield developed an approach to print skin equivalents. The material may play a future role in facilitating the healing of chronic wounds.

print skin equivalents technique

The technique is the first of its kind to simulate three layers of skin: the hypodermis, or fatty layer, the dermis, and the epidermis.

“You effectively have three different cell types. They all grow at different speeds,” said author Alan Smith. “If you try to produce tri-layered structures, it can be very difficult to provide each of the requirements of each different layer.”

To solve this problem, the scientists used suspended layer additive manufacturing (SLAM). They created a gel-like material to support the skin equivalent, twisting and altering the structure of the gel as it formed to create a bed of particles that can then support a second phase of gel injection.

During printing, the skin layers are deposited within the support gel, which holds everything in place. After printing, the team washed away the support material, leaving behind the layered skin equivalent.

If the researchers moved a needle through the supporting gel, it repaired itself faster than other similar techniques. This results in higher resolution printing than previous methods and allows for the printing of complicated skin structures.

The authors tested the skin substitute by cutting a hole in pig tissue and printing a skin equivalent to fill the hole. After culturing the model system for 14 days, they saw signs of wound repair.

“We used a stain that allowed us to quantify the integration we got between original material and tissue,” said author Liam Grover. “We were able to demonstrate some integration even after a short period of time.”

The team cannot assess chronic wound healing with the skin substitute because that process takes more time than their model allowed, which was only 14-21 days. However, their next step is to test longer, appropriate models for chronic deep wounds. The ultimate goal is to repair human skin and reduce scarring for all patient scenarios.


Story Source:

Materials provided by American Institute of PhysicsNote: Content may be edited for style and length.

انتخاب میزان فشار

Choose pressure level for all types of wounds with Simplex III devices

In the following cases, a pressure more than -125 mmHg and less than -150 mmHg can be used:

  1. High secretions wounds
  2. Vacuum therapy using white foam
  3. Vacuum therapy using abdovac kit

In the following cases, pressures less than -125 mmHg is recommended:

  1. Diabetic foot ulcers
  2. Damaged vessels
  3. Patients with a lower pain threshold

Note: In case of skin grafts, pressure of -50 to -80 mmHg should be used.

choose therapy mode

choose therapy mode in wound vacuum therapy

Variable therapy mode is a useful combination from increasing and decreasing blood flow.

Increasing blood flow:

  • Facilitate oxygenation
  • Nutrient supply

Decreasing blood flow

  • stimulation angiogenesis
  • Granulation tissue formation

 

Comparison variable pressure and continuous pressure

  • Variable pressure results more granulation tissue formation than continuous pressure.
  • Repeated mechanical simulations due pressure changes cause enhanced regeneration of wound edges so wound contraction in vacuum therapy with variable pressure is more than continuous pressure

 

Contraindications of variable therapy mode:

Applying variable pressure in some wound types can be harmful(contraindication):

*Continuous pressure can be used for all types of wounds without risk.

کرم ترمیم کننده زخم بدون اسکار

The first human trials of scarless wound healing cream

Researchers from The University of Western Australia (UWA; Perth, Australia) have partnered with industry to conduct a world-first study to investigate a new product—a topical scareless wound healing cream containing the drug PXS-6302 (Pharmaxis)—that has the potential to prevent or reduce scars forming after trauma and particularly following burn injury.

This research have started in Australia.

Kylie Sandy-Hodgetts, Mark Fear, and Fiona Wood, all from UWA Medical School and the Skin Integrity Research Institute UWA, are working with industry partner pharmaceutical company Pharmaxis, clinical trials facility Linear Clinical, the Burn Injury Research Unit, and Burns Service at Fiona Stanley Hospital.

Sandy-Hodgetts says skin scars placed a substantial physical and psychological burden on patients. “Current treatments aim to rectify the scar in the acute phase, such as during wound healing and scar maturation, through options such as compression therapy, silicone gel sheeting, or when the scar is established by cryotherapy, scar revision, or laser with limited outcomes at times,” she adds. “This new compound may potentially avoid the need for invasive procedures such as further surgery or laser procedures.”

The world-first human trial, led by Wood and Sandy-Hodgetts, aims to determine the safety and tolerability of the product in healthy volunteers, which will lead to further trials in burns and surgical patients.

“Scar formation following surgery has a huge impact on patient wellbeing and how they feel about themselves,” Sandy-Hodgetts comments.

“What we are hoping is that this new scarless wound healing cream may have the potential to improve scar outcomes in patients following surgery.”

Wood notes that it was exciting for the research team to explore a novel path to reduce scarring and to be moving closer to that goal: “Scar-less healing is the vision that has motivated our work over many decades”.

Pharmaxis CEO Gary Phillips says that the company is also very excited to see its expertise in fibrosis being applied to help patients with scarring.

“We have had a long and productive collaboration with researchers at UWA and this world-first trial of our drug PXS-6302 will establish whether the remarkable results seen in the pre-clinical models can be replicated in patients,” he states.

“Scarring can have a devastating and life-long impact on people who have suffered traumatic injuries. A topical cream to reduce scarring would have a significant role in treatment”.

oral nutritional

Oral nutritional supplements effective for hard-to-heal wounds

Specialised oral nutritional supplement can be a therapeutic option for hard-to-heal wounds, conclude Adriano A Mehl (Universidade Tecnológica Federal do Paraná, Curitiba, Brazil) and colleagues in the Journal of Wound Care.

“Hard-to-heal wounds [defined as those that fail to proceed through the healing phases of haemostasis, inflammation, proliferation, and tissue remodelling in three to four weeks] represent a silent epidemic,” Mehl et al write. “They affect a large fraction of the world’s population and pose a growing threat to public health, with a substantial negative economic impact.”

Based on the logic that nutritional intake plays an essential role in repairing damaged tissue, as has previously been established in the literature, the investigators conducted a prospective, randomised controlled assessment of the effects of nutritional supplements specialised in the repair of hard-to-heal wounds. The supplements used contained the amino acids proline and arginine, as well as high levels of vitamins A, C, and E, in addition to zinc and selenium. Mehl was the principal investigator.

Mehl, the principal investigator for the study, explained the choice underpinning this choice of nutritional make-up: “Although wound healing is a complex process, collagen synthesis is required for it to take place. This synthesis depends on proline and lysine hydroxylation, the presence of cofactors such as vitamins A, E and C, iron, zinc and selenium, and the oxygenation of cells. For this process to occur ideally, special attention must be given to factors such as adequate protein energy supply. In spite of this, little is known about the exact mechanism of some nutrients in the healing process, as well as their direct action on the healing process, supplementation dosage, and optimal period of use.”

Mehl and colleagues comment: “Awareness among health professionals of the important role that nutrition plays in overall wellness and disease treatment is very low, and should be encouraged. An early and timely nutritional intervention will help reverse the negative consequences of malnutrition. The use of a specialised oral nutritional supplement aimed at healing should be considered from the initial assessment as a tool of early intervention in wound treatment.

“An adequate nutritional status can be measured not only through wound evolution and resolution but also through absence of infections and other complications during the healing process. The specialised oral nutritional supplement tested achieved the nutritional goals and provided this study with results that corroborate the findings in the literature.”

Despite saying that the findings of this study are “promising”, the authors also say a larger study is needed to corroborate their results.

white foam

Creative Closure of Tunneling and Undermining Wounds with white foam

Wounds treated with negative pressure wound therapy (NPWT) are not often straightforward. They occur in interesting places, have anything from slough to hardware visible in the bases, and have nooks and crannies that are not visible to the clinicians peering into the wound. A gentle probe is necessary during wound assessment to identify tunnels and undermined areas. I prefer to gently probe first with my gloved finger (I have small hands) because I can identify hidden structures and other oddities. Then I will use a swab to measure how far the tunnel or undermining extends. Once hidden dead spaces have been identified, clinicians can select the best strategy to bring them to closure. Herein are several techniques employed by clinicians to close undermined and tunneled areas.

White foam is a favorite choice. Some foam-based NPWT manufacturers offer white foam, but not all. White foam is hydrophilic. It is intended to hold moisture next to structures like tendon, bone and hardware. The extent to which wound fluid is able to move through hydrophilic foams depends on the material that the foam consists of. Some foams are made of polyvinyl alcohol (PVA) material. This foam must remain moist or it will become quite hard, and has limited ability to move moisture through it. Check clinical guidelines, typically it is recommended that pressures be increased with PVA foam. Other manufacturers’ white foam is polyurethane (PUA). This is soft even when dry, and does not require pressures be increased to move fluid.

When using white foam to fill tunnels or undermined wound areas, make sure that you do not overfill the dead space. Although you want to fill to within 1 cm of the back of the tunnel or undermined area, it is preferable to allow the volume to collapse around the foam to speed granulation. Make sure that a sufficient amount of white foam protrudes from the opening so that it is easily identified at the dressing change.

While white foam is useful, it is not always available. Medicare and other third party payers do not cover it, so clinicians in the outpatient and home care settings have to find alternatives when there is hidden dead space to fill in a wound. Two materials that are readily available in most settings include gauze packing strips and wound non-contact layers. These materials have an advantage of allowing tunnels to collapse around it easily, but prevent seroma formation. It is difficult to use these materials for large undermined areas, however. While black foam might be preferable, the risk of breakage is real. A great way to use black foam safely in undermined areas or long wound tunnels is to roll it in a single layer of gauze or wound non-contact material. This technique gives insurance that all of the black foam will be removed while minimally impacting its ability to move moisture.

Some clinicians choose not to fill tunnels and undermined areas at all; rather they bolster the hidden dead space from above to promote wound closure. Below are the steps that are usually followed when bolstering undermined areas or tunnels.

  1. Carefully assess the area to be certain how far it extends.
  2. Drape the skin overlying the dead space.
  3. Apply a full thickness piece of foam on the draped skin overlying the entire dead space. Make sure the foam connects onto foam used to fill the wound. Drape the foam bolster with the rest of the wound, and complete the NPWT dressing application as usual.
  4. As the dressing pulls down and achieves target pressure, gently press over the bolstered area to ensure that the wound underlying the bolster has sealed.

The risk of this technique includes seroma or abscess formation, so the prescribing provider should always approve of this technique being employed.

In conclusion, hidden dead spaces must always be thoroughly cleansed at each dressing change to remove debris and reduce bioburden. Since irrigation of the areas may be challenging, a syringe can be a useful tool to irrigate. Closure of undermined and tunneled areas is essential in achieving wound healing success.

About the Author
Beth Hawkins Bradley, RN, MN, CWON is the director of Clinical Operations at Cardinal Health. She has been certified in the specialty of Wound, Ostomy, Continence nursing since 1990.

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