Lessons Learned From A Pilot Ex Vivo Translational Study

[Posted 2/Mar/2023]

AUDIENCE: General Surgery, Family Medicine

KEY FINDINGS: This study showed similar fluorescence of immuno-labeled prostate tissue samples and controls, failing to demonstrate the feasibility of intra-operative margin detection using PSMA immuno-labeling, due to marked tissue autofluorescence. The authors successfully developed a fluorescence device that could be used intraoperatively in a laparoscopic setting. Use of the infrared range as well as newly available antibodies could prove interesting options for future research.

BACKGROUND: Nerve-sparing techniques during radical prostatectomy have been associated with an increased risk of positive surgical margins. The intra-operative detection of residual prostatic tissue could help mitigate this risk. The objectives of the present study were to assess the feasibility of using an anti-prostate-specific membrane antigen (anti-PSMA) antibody conjugated with a fluorophore to characterize fresh prostate tissue as prostatic or non-prostatic for intra-operative surgical margin detection.

DETAILS: Fresh prostatic tissue samples were collected from transurethral resections of the prostate (TURP) or prostate biopsies, and either immunolabelled with anti-PSMA antibody conjugated with Alexa Fluor 488 or used as controls. A dedicated, laparoscopy-compliant fluorescence device was developed for real-time fluorescence detection. Confocal microscopy was used as the gold standard for comparison. Spectral unmixing was used to distinguish specific, Alexa Fluor 488 fluorescence from nonspecific autofluorescence. The average peak wavelength of the immuno-labeled TURP samples (n = 4) was 541.7 ± 0.9 nm and of the control samples (n = 4) was 540.8 ± 2.2 nm. Spectral unmixing revealed that these similar measures were explained by significant autofluorescence, linked to electrocautery. Three biopsy samples were then obtained from seven patients and also displayed significant nonspecific fluorescence, raising questions regarding the reproducibility of the fixation of the anti-PSMA antibodies on the samples. Comparing the fluorescence results with final pathology proved challenging due to the small sample size and tissue alterations.

Copyright © Wiley Periodicals LLC. All rights reserved

Source: Fiard, G., Hughes, C., Heus, R., et al. (2023). Intra-Operative Fluorescence-Based Detection Of Positive Surgical Margins During Radical Prostatectomy: Lessons Learned From A Pilot Ex Vivo Translational Study. Lasers Surg. Med.. 2023; 55(2): 226-232. Published: February, 2023. DOI: 10.1002/lsm.23627.

[Posted 8/May/2023]

AUDIENCE: Surgery, Internal Medicine, Nephrology

KEY FINDINGS: Using the largest cohort of adult kidney transplant recipients with IDD to date, the study team found that rates of evaluation and transplant were lower despite yielding equivalent outcomes. These data support consideration of adults with IDD for kidney transplant and underscore the urgent need for antidiscrimination initiatives to promote the receipt of equitable care for this population.

BACKGROUND: Improving equity in organ transplant access for people with intellectual and developmental disabilities (IDD) is a topic of social discourse in mainstream media, state legislation, and national legislation. However, few studies have compared evaluation rates, transplant rates, and outcomes among adults with and without IDD. Aim of this study was to compare rates of kidney transplant and transplant-specific outcomes between propensity–score matched groups of adults with end-stage kidney disease (ESKD [also referred to as end-stage renal disease (ESRD)]) with and without co-occurring IDD.

DETAILS: This retrospective cohort study included all Medicare inpatient and outpatient standard analytical files from 2013 through 2020. A total of 1,413,655 adult Medicare beneficiaries with ESKD were identified. Propensity–score matching was used to balance cohorts based on age, sex, race, follow-up duration, and Charlson Comorbidity Index. The matched cohorts consisted of 21,384 adults with ESKD (10,692 of whom had IDD) and 1258 kidney transplant recipients (629 of whom had IDD). Data were analyzed between June 1, 2022, and August 1, 2022. Of the 21,384 propensity–score matched adults with ESKD, the median (IQR) age was 55 (43-65) years, 39.2% were male, 27.4% were Black, 64.1% were White, and 8.5% identified as another race or ethnicity. After propensity score matching within the ESKD cohort, 633 patients with IDD (5.9%) received a kidney transplant compared with 1367 of adults without IDD (12.8%). Adults with IDD were 54% less likely than matched peers without IDD to be evaluated for transplant (odds ratio, 0.46; 95% CI, 0.43-0.50) and 62% less likely to receive a kidney transplant (odds ratio, 0.38; 95% CI, 0.34-0.42). Among matched cohorts of kidney transplant recipients, rates of perioperative complications, readmission, and graft failure were similar for adults with and without IDD.

Copyright © This is an open access article distributed under the terms of the CC-BY License. © 2023 Hand BN et al. JAMA Surgery.

Source: Hand, B. N., Hyer, J. M., Schenk, A., et al. (2023). Comparing Kidney Transplant Rates and Outcomes Among Adults With and Without Intellectual and Developmental Disabilities. JAMA Surg.. 2023; 158(4): 386-392. Published: April, 2023. DOI: 10.1001/jamasurg.2022.7753.

[Posted 24/Mar/2023]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: C. auris case counts have increased for many reasons, including poor general infection prevention and control (IPC) practices in healthcare facilities. Case counts may also have increased because of enhanced efforts to detect cases, including increased colonization screening, a test to see if someone has the fungus somewhere on their body but does not have an infection or symptoms of infection. The timing of this increase and findings from public health investigations suggest C. auris spread may have worsened due to strain on healthcare and public health systems during the COVID-19 pandemic.

BACKGROUND: Candida auris (C. auris), an emerging fungus considered an urgent antimicrobial resistance (AR) threat, spread at an alarming rate in U.S. healthcare facilities in 2020-2021, according to data from the Centers for Disease Control and Prevention (CDC) published in the Annals of Internal Medicine. Equally concerning was a tripling in 2021 of the number of cases that were resistant to echinocandins, the antifungal medicine most recommended for treatment of C. auris infections. In general, C. auris is not a threat to healthy people. People who are very sick, have invasive medical devices, or have long or frequent stays in healthcare facilities are at increased risk for acquiring C. auris. CDC has deemed C. auris as an urgent AR threat, because it is often resistant to multiple antifungal drugs, spreads easily in healthcare facilities, and can cause severe infections with high death rates.

DETAILS: "The rapid rise and geographic spread of cases is concerning and emphasizes the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control," said CDC epidemiologist Dr. Meghan Lyman, lead author of the paper.

As further explained in the article, C. auris has spread in the United States since it was first reported in 2016, with a total of 3,270 clinical cases (in which infection is present) and 7,413 screening cases (in which the fungus is detected but not causing infection) reported through December 31, 2021. Clinical cases have increased each year since 2016, with the most rapid rise occurring during 2020-2021. CDC has continued to see an increase in case counts for 2022. During 2019-2021, 17 states identified their first C. auris case ever. Nationwide, clinical cases rose from 476 in 2019 to 1,471 in 2021. Screening cases tripled from 2020 to 2021, for a total of 4,041. Screening is important to prevent spread by identifying patients carrying the fungus so that infection prevention controls can be used.

The CDC's Antimicrobial Resistance Laboratory Network, which provides nationwide lab capacity to rapidly detect antimicrobial resistance and inform local responses to prevent spread and protect people, provided some of the data for this report. CDC worked to significantly strengthen laboratory capacity, including in state, territorial, and local health departments, through supplemental funding supported by the American Rescue Plan Act. These efforts include increasing susceptibility testing capacity for C. auris from seven Regional Labs to more than 26 labs nationwide.

CDC continues to work with state, local, and territorial health departments and other partners to address this emerging threat to public health. Review more information on C. auris, the Antimicrobial Resistance Threats Report that identified C. auris as an urgent threat in the United States, or the WHO fungal priority pathogen list that identifies C. auris as a priority globally.

Copyright © CDC. All rights reserved.

Source: Increasing Threat of Spread of Antimicrobial-resistant Fungus in Healthcare Facilities. Centers for Disease Control and Prevention. 2023; 320. Published: March 20, 2023. https://www.cdc.gov/media/releases/2023/p0320-cauris.html.

[Posted 1/Feb/2023]

AUDIENCE: General Surgery, Family Medicine

KEY FINDINGS: OCT is an effective method for evaluating changes in aging skin. The results illustrate a decline in skin density with chronological age. Additionally, it was illustrated that structural change in the epidermis and dermis does occur, however on a microscopic scale, there are no significant differences based on laterality. OCT holds promise as a noninvasive technique for characterization of aging skin. Its utility and application in the clinical management and treatment of aged skin requires further research; however, the technology has potential to personalize therapies based on objective findings.

BACKGROUND: The skin aging exposome encompasses internal and external factors that contribute to clinical signs of facial aging. Aging skin can be characterized by distinctive features such as wrinkles, lentigines, elastosis, and roughness. Optical coherence tomography (OCT) is capable of noninvasively measuring skin characteristics. This study aimed to assess bilateral features using OCT to explore temporal skin changes among decades and potential changes in facial skin aging based on laterality.

DETAILS: A total of 97 subjects between 20 and 89 years old with Fitzpatrick skin types I to IV were enrolled. VivoSight, a Multi-Beam OCT system intended to gather topographical and histological images of skin, was used to scan the area inferolateral to the lateral canthus, bilaterally. Investigators compared characteristics of skin roughness, attenuation coefficient and blood flow across age groups and based on laterality to determine any differences. Only data from successful OCT scans were used. Seventy subjects, 10 from each specified decade, had successful bilateral scans and were thus included in the analysis. Chronological aging was characterized by significantly decreased dermal attenuation coefficient with increased age. Skin roughness measurements showed trends of increased roughness with age; however, no statistically significant changes were seen between groups. Qualitative differences amongst scans taken on right and left sides of the face showed no significance regarding roughness, density or blood flow at depths ranging from 0.05 to 0.5 mm.

Copyright © Wiley Periodicals LLC. All rights reserved.

Source: Vingan, N. R., Parsa, S., Barillas, J., et al. (2023). Evaluation and Characterization of Facial Skin Aging Using Optical Coherence Tomography. Lasers Surg. Med.. 2023; 55(1): 23-24. Published: January, 2023. DOI: 10.1002/lsm.23611.

[Posted 27/Jan/2023]

AUDIENCE: Ob/Gyn, Neurology, Family Medicine

KEY FINDINGS: Low-normal cervical length (25-30 mm) as measured before in-utero laparotomy-assisted fetoscopic spina bifida repair may increase the risk of adverse perinatal outcomes, including PPROM and preterm birth, leading to higher rates of neonatal complications. These data warrant further research and are of critical relevance for clinical teams considering the eligibility of patients for in-utero spina bifida repair. Based on this evidence, patients with a low-normal cervical length should be aware of their increased risk for adverse perinatal outcome.

BACKGROUND: Aim of this study i to determine if preoperative cervical length in the low-normal range increases the risk of adverse perinatal outcome in patients undergoing fetoscopic spina bifida repair.

DETAILS: This was a retrospective cohort study of patients who underwent fetal spina bifida repair between September 2014 and May 2022 at a single center. Cervical length was measured on transvaginal ultrasound during the week before surgery. Eligibility for laparotomy-assisted fetoscopic spina bifida repair was as per the criteria of the Management of Myelomeningocele Study, although maternal body mass index (BMI) up to 40 kg/m2 was allowed. Laparotomy-assisted fetoscopic spina bifida repair was performed, with carbon dioxide insufflation via two 12-French ports in the exteriorized uterus. All patients received the same peri- and postoperative tocolysis regimen, including magnesium sulfate, nifedipine and indomethacin. Postoperative follow-up ultrasound scans were performed either weekly ( 32 weeks' gestation) or twice a week (< 32 weeks). Perinatal outcome was compared between patients with a preoperative cervical length of 25-30 mm vs those with a cervical length > 30 mm. Logistic regression analyses and generalized linear mixed regression analyses were used to predict delivery at less than 30, 34 and 37 weeks' gestation. The study included 99 patients with a preoperative cervical length > 30 mm and 12 patients with a cervix 25-30 mm in length. One further case which underwent spina bifida repair was excluded because cervical length was measured > 1 week before surgery. No differences in maternal demographics, gestational age (GA) at surgery, duration of surgery or duration of carbon dioxide uterine insufflation were observed between groups. Cases with low-normal cervical length had an earlier GA at delivery (median (range), 35.2 (25.1-39.7) weeks vs 38.2 (26.0-40.9) weeks; P = 0.01), higher rates of delivery at < 34 weeks (41.7% vs 10.2%; P = 0.01) and < 30 weeks (25.0% vs 1.0%; P < 0.01) and a higher rate of preterm prelabor rupture of membranes (PPROM) (58.3% vs 26.3%; P = 0.04) at an earlier GA (mean ± SD, 29.3 ± 4.0 weeks vs 33.0 ± 2.4 weeks; P = 0.05) compared to those with a normal cervical length. Neonates of cases with low-normal cervical length had a longer stay in the neonatal intensive care unit (20 (7-162) days vs 9 (3-253) days; P = 0.02) and higher rates of respiratory distress syndrome (50.0% vs 14.4%; P < 0.01), sepsis (16.7% vs 1.0%; P = 0.03), necrotizing enterocolitis (16.7% vs 0%; P = 0.01) and retinopathy (33.3% vs 1.0%; P < 0.01). There was an association between preoperative cervical length and risk of delivery at < 30 weeks which was significant only for patients with a maternal BMI < 25 kg/m2 (odds ratio, 0.37 (95% CI, 0.07-0.81); P = 0.02).

Copyright © International Society of Ultrasound in Obstetrics and Gynecology. All rights reserved.

Source: Corets, M. S., Corroenne, R., Johnson, B., et al. (2022). Effect of Preoperative Low-Normal Cervical Length on Perinatal Outcome After Laparotomy-Assisted Fetoscopic Spina Bifida Repair. Ultrasound Obstet Gynecol. 2023; 61(1): 74-80. Published: January, 2023. DOI: 10.1002/uog.26070.

[Posted 27/Dec/2022]

AUDIENCE: Ob/Gyn, Family Medicine

KEY FINDINGS: The preoperative difference in UVF between the recipient and donor twins confirms the pathophysiology of TTTS. Postoperatively, the substantial increase in UVF of the donor twin and the relatively small increase in UVF of the recipient twin confirm that ablation of the vascular communications resulted in rapid improvement in perfusion of the donor twin.

BACKGROUND: Twin–twin transfusion syndrome (TTTS) is characterized by unequal hemodynamics between the twins. It was aimed to assess preoperatively the difference in umbilical vein flow (UVF) between the recipient and donor monochorionic diamniotic twins and evaluate the change in UVF following laser surgery in both twins.

DETAILS: This was a retrospective cohort study of differences in UVF that occurred following laser surgical treatment of TTTS. Sonographic assessment of the umbilical vein before and 24& h after fetoscopic laser surgery for TTTS was performed. Umbilical vein diameter and time-averaged maximum velocity were measured, and UVF per kg (UVF/kg) was converted into a Z-score by a calculator created using gestational age as an independent variable. Z-score values were converted into centiles, which were evaluated statistically. Median differences in UVF/kg centile values were adjusted for TTTS stage and presence of arterioarterial anastomoses. The study population consisted of 363 TTTS patients. The adjusted preoperative median difference in UVF/kg centile between the recipient vs donor twin was 17.9% (-17.1% to 57.6%), P < 0.0001. The adjusted median difference in UVF/kg centile between the postoperative vs preoperative period among recipients was 2.2% (-10.8% to 13.8%), P < 0.0001, while the adjusted median difference among donors was 27.3% (8.2%-34.6%), P < 0.0001.

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Saab, R. H., DeVore, G. R., Monson, M., et al. (2022). Correction of Fetal Umbilical Vein Flow Imbalance Following Laser Surgery for Twin-Twin Transfusion Syndrome. Ultrasound Obstet Gynecol. 2022; 60: 774-779. Published: December, 2022. DOI: 10.1002/uog.26041.