Virtual Crossmatching For Faster Kidney Transplantation

Kidney transplantation can be safely performed with virtual crossmatching of donor and recipient without the need for a prospective physical crossmatch, according to a retrospective review.

“We think virtual crossmatching should become the standard of care for the majority of patients,” Dr. Vinayak S. Rohan of the Medical University of South Carolina, in Charleston, told Reuters Health by email.

Prior to kidney transplant, donor-recipient compatibility is assessed by physical crossmatching, usually by flow cytometry, at most programs. Virtual crossmatching (VXM) relies on complete HLA typing of the donor and current antibody assessment of the recipient, which can be performed quickly and allows for timelier organ allocation decisions.

Dr. Rohan and colleagues compared kidney transplant outcomes, principally the mean cold ischemic times (CIT), between 505 patients transplanted before their 2017 implementation of VXM and 227 patients transplanted using VXM.

After implementation, the mean CIT decreased from 16.67 hours to 14.5 hours (P=0.002), the researchers report in Journal of the American College of Surgeons.

Delayed graft-failure rates did not differ significantly between the pre-implementation (19%) and post-implementation (17%) eras, even though there were more donation after cardiac death (DCD) and higher (less favorable) Kidney Donor Profile Index (KDPI) donors in the post-implementation era.

The rates of one-year graft loss, patient death and biopsy-proven acute rejection rates did not differ between the two eras.

In multivariable modeling that adjusted for baseline characteristics, patients transplanted in the post-implementation era had an estimated 2.35-hour reduction in CIT (P<0.001) and 26% lower odds of developing delayed graft failure (P=0.17).

“We have known for years that VXM is a safe technology,” Dr. Rohan said. “This article not only reaffirms the safety of VXM, but also the outcomes, in terms of cold ischemia times and delayed graft function.”

“The ability to predict the crossmatch and schedule the operation in advance leads to less potential ‘middle of the night’ transplants, improving quality of life not only of patients but surgeons as well,” he said.

Dr. Raja Rajalingam of the University of California, San Francisco, who recently showed that a VXM-based strategy facilitates sharing of DCD kidneys for highly sensitized recipients, told Reuters Health by email, “Virtual crossmatching should become the standard of care at the national level.”

“It is considered to be challenging to perform virtual crossmatch for broadly sensitized patients (due to previous transplantation, pregnancies, and blood transfusions),” said Dr. Rajalingam, who was not involved in the new research. “However, it is not clear how many of the 29 (broadly sensitized) patients (in this study) received a kidney transplantation based on virtual crossmatch.”

He expressed surprise that the decrease in CIT was only about two hours with VXM. Based on the four to five hours required to perform pretransplant flow cytometry physical crossmatch, he would have expected a greater reduction.

Source : Medscape

‘No FGM’ Campaign Started by Egypt Doctors

Doctors in Egypt have taken time out of their surgeries for a campaign to raise awareness of the dangers of female genital mutilation (FGM) after the death of a 12-year-old girl, saying they do not want their white coats “stained with blood.”

Genital cutting of girls was banned in Egypt in 2008, but it remains persistent – a 2016 survey by the U.N. Children’s Fund showed 87% of women and girls aged 15-49 had undergone the procedure.

The campaign, entitled “White Coats,” saw posters with the slogans “No to FGM” and “FGM is a Crime” put up at a Cairo metro station, where doctors in white coats gave out leaflets about the dangers of the practice.

Organizer Randa Fakhr El Deen, head of the NGOs’ Union Against Harmful Practices on Women and Children, said the doctors had faced challenges from proponents of FGM at the station, but the campaign was important.

“We want to send a message to other doctors that we do not want our white coats to be stained with blood as well as to citizens that medicine refuses this practice,” she told the Thomson Reuters Foundation.

“Some ultraconservatives were not convinced of what we were saying, but we opened a discussion with them, responded to their arguments and answered all their questions.”

World leaders have pledged to eradicate FGM by 2030, but campaigners say the ancient ritual, which typically involves the partial or total removal of the external genitalia, remains deeply entrenched in many places.

It can cause long-lasting mental and physical health problems including chronic infections, menstrual problems, infertility, pregnancy and childbirth complications.

Last month Egyptian authorities arrested a retired doctor on charge of carrying out illegal FGM surgery and causing the death of a 12-year-old girl. The girl’s parents were also arrested.

All have since been released, but investigations are continuing and campaigners against FGM say they expect them to face trial.

The ritual is underpinned by the desire to control female sexuality, but is often justified for cultural or religious reasons in conservative societies.

Women and children’s rights groups in Egypt say the ban has not been well enforced and that much of society is permissive of FGM, which is widely practised by both Christians and Muslims.

The majority of FGM procedures are carried out by doctors and nurses at private clinics, with the rest done at home, according to the Egypt Demographic and Health Survey of 2014.

“It is a religious thing. Do you want to change religion?” said metro user Ibrahim Hassan in response to the “White Coats” campaign. “You only listen to what the West is saying.”

In response, Fakhr El Deen told Hassan that FGM had no basis in religion and was not taught in medical schools in Egypt.

Source : Medscape

No Reduction in SSIs With Strict Surgical Attire Policy

Implementing policies that require surgical staff to wear surgical jackets and bouffants in the operating room (OR) does not decrease the risk for surgical site infections (SSIs), according to a study published online today in JAMA Surgery.

“[T]he results of this study suggest that surgical jackets and bouffants are neither beneficial nor cost-effective in preventing SSIs,” write Bradley W. Wills, MD, University of Alabama at Birmingham, and colleagues.

Approximately 300,000 SSIs occur annually in the United States, accounting for one fifth of all hospital-acquired infections and costing the US healthcare system an estimated $10 billion each year.

Although some evidence supports implementation of certain OR attire policies (such as use of gloves and impermeable surgical gowns) to help prevent SSIs, data are lacking on the association between use of surgical jackets and bouffants and infections.

Wills and colleagues performed a retrospective cohort study to investigate whether mandating use of surgical jackets and bouffants in the OR was linked to a lower incidence of SSIs.

The study included 34,042 inpatient surgical encounters at a large academic tertiary care hospital between January 2017 and October 2018. The researchers compared three periods within this time.

During the first period (8 months), no bouffants or surgical jackets were required. During the second period (6 months), surgical jackets were mandated, and during the third period (8 months), surgical jackets and bouffants were required.

Despite the dress code changes, SSI risk remained relatively constant throughout the time frame, with no significant difference between the three periods (1.01% vs 0.99% vs 0.83%; P = .28).

Similarly, the investigators found no significant difference between the periods in risk for mortality (1.83% vs 2.05% vs 1.92%; P = .54), postoperative sepsis (6.60% vs 6.24% vs 6.54%; P = .54), or wound dehiscence (1.07% vs 0.84% vs 1.06%; P = .20).

The researchers calculated that use of surgical jackets during the 14 months of the second and third study periods cost an additional $264,760.78.

“The results add to the growing body of research that there is no clear benefit to bouffants and surgical jackets in the quest to decrease the incidence of SSIs,” the authors conclude.

“Institutions should evaluate their own data to determine whether recommendations by outside governing organizations are beneficial and cost-effective.”

In an accompanying editorial, Radwan Dipp Ramos, MD, and Kamal M. F. Itani, MD, both from the Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts, agree that sufficient evidence now exists to show that these policies, although well-intentioned, do not reduce SSI risk and raise hospital expenditure.

Ramos and Itani, who is also with Boston University and Harvard Medical School, also stress the need to remember common-sense recommendations regarding OR attire. These include frequent laundering of cloth caps, they say.

Staff must remove headgear, mask, and shoe covers outside restricted areas and use new ones if they return to the OR. When leaving restricted areas for another case, staff should also change scrubs or cover them with a protective coat. And they should not be allowed to enter the OR wearing scrubs from home.

“Short of having best evidence in any of those areas, myth and reality will continue to coexist, and our common sense augmented by available evidence should prevail over emotions and careless practices,” the editorialists conclude.

Source : Medscape

Tramadol Linked to Increased Hip Fracture Risk in Elderly

Older patients treated with the pain medication tramadol show significant increases in the risk of hip fracture compared with those using codeine or commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), new research shows.

“Considering the significant impact of hip fracture on morbidity, mortality, and healthcare cost, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” first author Jie Wei, PhD, an associate professor of epidemiology at Xiangya Hospital, Central South University, China, told Medscape Medical News.

In commenting on the research, Shailendra Singh, MD, noted that the “article clearly reinforces [prior] knowledge…that opiates are associated with an increased risk of falls and fractures.”

The American Geriatric Society BEERS criteria for inappropriate drugs for the elderly, for instance, lists tramadol and opiates as drugs to avoid in patients with increased risk of falls and fractures, added Singh, who is rheumatology medical director of the White River Medical Center in Batesville, Arkansas, and was not involved with the current study.

Increased Risk of Hip Fracture With Tramadol Even Compared With Codeine  

The new study, published this month in the Journal of Bone and Mineral Research, involved data on 146,956 patients in the United Kingdom who were age 50 years and older and enrolled in The Health Improvement Network (THIN).

The patients had initiated treatment with tramadol between 2000 and 2017 for noncancer-related pain, and had no history of hip fracture, cancer, or opioid use disorder.

In the propensity-matching analysis, those initiating tramadol were matched 1:1 with well-balanced characteristics to patients identified as initiating codeine during the same period (146,956 in each group).

Equal-numbered groups were also matched between tramadol and naproxen (115,109 in each group) or ibuprofen (107,438 per group), both NSAIDs, or celecoxib (43,130 per group) or etoricoxib (27,689 per group), which are both cyclooxygenase‐2 inhibitors.

Participants in the matched groups had a mean age of 65 and 56.9% were women.

For the primary outcome of the incidence of hip fracture over 1 year, the risk was higher for tramadol compared with codeine (hazard ratio [HR], 1.28), with 518 cases of hip fracture (3.7 per 1000 person-years) in the tramadol cohort and 401 (2.9 per 1000 person-years) in the codeine cohort.

Likewise, the risk was higher with tramadol compared with naproxen (HR, 1.69), ibuprofen (HR, 1.65), celecoxib (HR, 1.85), and etoricoxib (HR, 1.96).

A sensitivity analysis restricted to individuals aged 60 or older showed no major differences in the associations for all of the drug groups.

“The sensitivity analyses had similar results, indicating that the observed associations were robust and raising a concern on the potential risk of hip fracture among initiators of tramadol use,” the authors say.

The increased risk compared with the initiation of codeine is particularly notable, as codeine is regarded as a weak opioid and often used in a similar context as tramadol, Wei noted.

“The risk of incident hip fracture among tramadol initiators was not only higher than that among NSAIDs initiators, but also higher than that among codeine initiators, suggesting that the confounding by indication may not substantially account for an increased risk of hip fracture for tramadol,” she observed.

She added that “this was further supported by the evidence that risk factor profiles between initial prescription of tramadol and that of codeine were similar even before propensity-matching, except a few (for instance BMI was higher among tramadol than codeine prescriptions).”

“Nevertheless, as in all observational studies, we can’t rule out the impact of potential residual confounders when comparing the risk of hip fracture between initial prescription of tramadol and other pain-relief medications,” Wei stressed.

Tramadol Seen as Beneficial NSAID Alternative for Pain

Tramadol is seen as a valuable analgesic alternative to NSAIDs, with perceived lower cardiovascular and gastrointestinal effects while providing a reduced risk of addiction and respiratory depression compared with traditional opioids, the authors note.

Guidelines of professional organizations recommend tramadol for pain under various conditions, including the most recent guidelines of the American College of Rheumatology (ACR), which conditionally recommend tramadol for the treatment of knee or hip osteoarthritis, “including when patients may have contraindications to NSAIDs, find other therapies ineffective, or have no available surgical options.”

Use of the drug has been on the rise worldwide in recent decades, with one survey showing a 22.8% increase in tramadol prescriptions in the US from 2012 to 2015.

The authors note that important limitations of the study include the fact that the THIN database does not include measures on two potentially important confounders — bone density and frailty.

Singh said it’s unknown whether propensity score matching can adjust for important factors, such as the severity of disease: “(For instance), people with severe osteoporosis are at a higher risk of fracture, compared to moderate…the lower the T-score, the higher the risk of fracture.”

Link Between Increased Risk of Falls and Tramadol?
Don’t Prescribe It First-Line

As reported by Medscape Medical News, Wei and her colleagues showed an association between tramadol use and a higher risk of all-cause mortality among patients in the THIN network in a study published last year.

The specific mechanisms linking tramadol use to an increased risk of mortality remain unclear, however.

And that study, which — as opposed to the current one — was limited to patients with osteoarthritis pain, showed the increased mortality risk did not extend to those treated with codeine.

Although the mechanisms that may explain the increased risk of fracture are not known, Wei and colleagues note previous research suggesting an effect of tramadol in activating mu-opioid receptors while suppressing central serotonin and norepinephrine reuptake, which can be linked to the risk of seizures, dizziness, and/or delirium — all of which could increase the risk of fall.

“In fact, several studies have reported that tramadol use was indeed associated with a higher risk of fall, which is a critical risk factor for fracture,” they note.

“All these studies appear to suggest that relation of tramadol to the risk of hip fracture may be, at least partly, through its effect on fall,” they surmise.

“In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice.”

Singh agrees. While underscoring that further studies are needed to determine the mechanism of action in the increased hip fracture risk, he concluded that “opiates of any kind, including tramadol, should not be used as a first line drug for pain management in any setting.”

Source : Medscape

How does it look like to drain the entire Ocean ?

Three fifths of the Earth’s surface is under the ocean, and the ocean floor is as rich in detail as the land surface with which we are familiar. This animation simulates a drop in sea level that gradually reveals this detail. As the sea level drops, the continental shelves appear immediately. They are mostly visible by a depth of 140 meters, except for the Arctic and Antarctic regions, where the shelves are deeper. The mid-ocean ridges start to appear at a depth of 2000 to 3000 meters. By 6000 meters, most of the ocean is drained except for the deep ocean trenches, the deepest of which is the Marianas Trench at a depth of 10,911 meters.

So , how does it look like to drain the entire ocean ? Lets see ….

Source : NASA

Handheld 3D Printer Delivers Skin-Precursor Sheets Directly to Full-Thickness Burns

A new handheld 3D printer can be used to deliver skin-precursor sheets directly to wound beds and improve healing in full-thickness burns, according to a preclinical study in a porcine model.

“The ability to consistently deliver (human) cells in a matrix and onto practically relevant wound surfaces, i.e., of arbitrary size and topology, has been a significant limitation that we believe has been overcome with our handheld instrument,” Dr. Alex Guenther of the University of Toronto, in Canada, told Reuters Health by email.

Large burn areas often leave insufficient healthy skin to use as autologous skin grafts. Acellular biodegradable scaffolds have been used as alternatives, and different cellular approaches using patient-derived autologous or donor-derived allogeneic cells are under development.

Dr. Guenther and colleagues developed a handheld 3D bioprinter designed to deliver a fibrinogen-based bioink containing mesenchymal stromal cells directly onto burn-wound surfaces of arbitrary size, shape and topography.

A burn area of 2,000 cm2 (similar to an average burn area of the human posterior trunk or about 10% of total body surface) would require about 40 mL of biomaterial with 40 million cells in total, with a deposition time of 70 minutes, the researchers report in Biofabrication.

The time required to cover a full-thickness burn wound size of 5×5 cm took an average of 0.89 min, using 480 uL of biomaterials with a total of 480,000 cells.

The researchers treated full-thickness burn wounds on four porcine models using the handheld instrument and found that the wounds were uniformly covered with the deposited material immediately after delivery.

After 28 days, the treated wounds showed superior healing profiles with a reduction in inflammation, scarring, and contraction, compared with untreated burns and burns treated with acellular materials.

Histologically, treated wounds showed epidermal cell repopulation in normal ranges, whereas burn controls and acellular treatments showed regions with poor cell repopulation in addition to localized areas with hyperplasia or hypoplasia.

“Cell delivery of bioprinting should in many clinical cases probably not be done with a printer that is scaled to patient dimensions,” Dr. Guenther said. “That would make for a very bulky instrument. In contrast, we believe the demonstrated handheld device is advantageous. Also, because its form is similar to another handheld instrument routinely used by burn surgeons for many decades: a dermatome.”

Co-author Dr. Marc G. Jeschke of Sunnybrook Health Sciences Centre, also in Toronto, told Reuters Health by email, “This could change the way we practice for burn patients and patients with large wounds as we could restore a patients skin with no scar, no pain as we avoid donor sites and a significantly shortened hospital stay from months to weeks.”

“We have not shown that printing can restore autologous skin of a patient yet,” he said. “The issue at this time is showing efficacy, but this is being studied.”

Source : Medscape