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.

A Case Series

[Posted 13/Jan/2026]

AUDIENCE: General Surgery, Dermmatology, Internal Medicine

KEY FINDINGS: While hypopigmentation is rare with PSL treatment, it can occur even with conservative low-fluence settings and adequate intervals between sessions. One possible mechanism is thermal beam- stacking, where slow hand movement during treatment may lead to repeated pulses on the same area. This can result in localised thermal accumulation, potentially causing subcellular disruption of melanosomes without overt melanocyte loss. These findings suggest the need for clinician vigilance in monitoring for hypopigmentation, as re-pigmentation may not be achievable. Larger, controlled studies are needed to clarify risk factors and guide safer practice.

BACKGROUND: Picosecond lasers (PSL) are increasingly used for treating melasma, with fewer adverse effects reported compared to Q-switched lasers (QSL). However, the incidence of hypopigmentation following PSL treatment remains unexplored in detail. This case series aims to explore outcomes of hypopigmentation following PSL therapy in patients with melasma, and explore potential contributing factors.

DETAILS: A retrospective chart review identified four patients with hypopigmentation following PSL treatment for melasma, including one referral from another clinic. Across the cohort, 796 patients underwent 3096 sessions between 2021 and 2025. Treatments used 755 and/or 1064-nm wavelengths at low fluences, with intervals of 4–12 weeks. Three in-clinic patients (0.38%, 95% CI 0.13%–1.10%) and one referral developed hypopigmentation. Changes occurred across both wavelengths and beam profiles. Histology demonstrated preserved melanocyte density with reduced melanin pigment and melanosome content. None of the cases showed meaningful re-pigmentation at 6-month follow-up. No cases of post-inflammatory hyperpigmentation (PIH) were observed.

Copyright © Wiley Periodicals LLC. All rights reserved

Source: Hang, X. and Lim, D. S. Hypopigmentation Following Picosecond Laser Treatment for Melasma: A Case Series. Lasers Surg. Med.. 2025; Published: December, 2025. DOI: 10.1002/lsm.70077.

[Posted 27/Oct/2025]

AUDIENCE: Infectious Disease, Microbiologists

KEY FINDINGS: Enhanced antibiotic performance observed in preclinical mouse models. Potential to improve treatment outcomes for multiple intracellular bacterial infections. Ongoing efforts include mechanism elucidation and patent development.

BACKGROUND: Antibiotic resistance has severely limited the effectiveness of conventional treatments against persistent bacterial infections. Some pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, and Salmonella enterica, can survive inside immune cells, remaining dormant and shielded from antibiotic action. The increasing prevalence of such infections underscores an urgent need for alternative approaches that do not rely solely on developing stronger antibiotics.

DETAILS: Researchers at the University of North Carolina (UNC) School of Medicine, led by Dr. Brian Conlon and Dr. Kuan-Yi Lu, identified a novel small molecule that modifies immune cell behavior to enhance antibiotic performance. Instead of directly targeting bacteria, the molecule reprograms the host's immune cells to activate dormant pathogens, rendering them more susceptible to antibiotic killing.

The team screened approximately 5,000 small molecules through the UNC Small Molecule Screening Core. They used luminescent reporter strains of S. aureus to identify compounds that triggered bacterial activation. The most promising compound was subsequently tested in mouse models, where it significantly improved antibiotic efficacy when administered alongside standard treatments.

In animal models, the selected molecule substantially improved pathogen clearance for S. aureus, M. tuberculosis, and S. enterica when used in combination with existing antibiotics. This finding supports a new therapeutic concept: targeting the host cell environment can potentiate antibiotic activity and overcome intracellular bacterial persistence. The discovery presents an innovative direction for combating infections that evade standard therapy.

Copyright © UNC School of Medicine. All rights reserved.

Source: Conlon, B. and Kuan-Yi, L. UNC Researchers Discover Method to Combat Antibiotic Treatment Failure. UNC Health Newsroom. 2025; Published: October 14, 2025.

A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines

[Posted 14/Oct/2025]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: This study highlights how antipsychotic prescribing in dementia is discordant with current NICE guidelines on both duration and dose. More than half of those who discontinued their treatment then restarted treatment. These findings emphasise a persistent gap between clinical guidelines and real-world prescribing, underscoring the need for interventions that prioritise safety and person-centred dementia care.

BACKGROUND: In the UK, it is recommended by the National Institute for Health and Care Excellence (NICE) that if antipsychotics are initiated in people living with dementia, treatment should be at the lowest dose for the shortest time possible (1-3 months). In this study, authors aimed to investigate how dose and duration of antipsychotic medication adhere to UK clinical guidelines and explore treatment restart details in those who stop treatment.

DETAILS: Authors did a retrospective cohort study using longitudinal UK primary care data from the IQVIA Medical Research Database. Authors included people living with dementia aged 60-85 years who received their first antipsychotic prescription between Jan 1, 2000, and Dec 31, 2023. Individuals with any previous antipsychotic prescriptions in their records more than 1 year before a dementia diagnosis and those who had missing social deprivation information were excluded from the study. Duration of first and subsequent antipsychotic treatment episodes, medication dosage, and treatment discontinuation and reinitiation rates were investigated. Duration and discontinuation were defined by grouping consecutive prescriptions into treatment episodes using the waiting time distribution method (80% inter-arrival density, 59 days). Daily doses were derived from strength and frequency information and categorised as low or moderate or high based on established minimum effective dose equivalences. People with lived experience of dementia care contributed throughout this project, shaping the research question and advising on interpretation and dissemination strategies. In the dataset search, authors identified 108,910 people with a record indicating dementia at any time. In total, 99,091 cases were excluded (ie, individuals with no antipsychotic prescription between the ages of 60 and 85 years between 2000 and 2023, a previous history of antipsychotics, missing deprivation information, or only one eligible prescription). Authors included 9819 people living with dementia aged 60-85 years who received their first antipsychotic prescription between 2000 and 2023 in the study. 5310 (54.1%) were female and 4509 (45.9%) were male, with a mean age of 77.1 years (SD 5.6 years), and ethnicity data were not available. The first treatment episode lasted a median of 7 months (IQR 6.6-8.7), exceeding NICE guidelines of 1-3 months and 18.1% [95% CI 17.4-18.9]) were initiated on a prescription above the minimum effective dose (ie, low dose). Of the 1781 participants who started on a moderate or high dose, 519 (29.1%) had a moderate or high dose in all quarters of the first year of treatment. 1 year after treatment initiation, 5136 (78.3%) of 6559 eligible individuals remained on medication (48.9% [95% CI 47.7-50.1] on low dose, 14.8% [13.9-15.6] on moderate or high dose of haloperidol, olanzapine, quetiapine or risperidone; and 14.6% [13.8-15.5] on other antipsychotics). Of the 5547 individuals eligible to restart treatment after initial discontinuation, 3106 (56%) restarted with a median treatment duration of 2.6 months (IQR 0.0-9.9).

Copyright © Elsevier Ltd. All rights reserved.

Source: Smsith, H. C., Petersen, I., Hayes, J. F., et al. (2024). Antipsychotic Prescriptions in People With Dementia in Primary Care: A Cohort Study Investigating Adherence of Dose and Duration to UK Clinical Guidelines. The Lancet Psychiatry. 2025; 12(10): 758-767. Published: October, 2025. DOI: 10.1016/S2215-0366(25)00261-5.

A Retrospective Repeated Cross-Sectional Study

[Posted 3/Oct/2025]

AUDIENCE: Family Medicine, Infectious Disease

KEY FINDINGS: Medicare beneficiaries aged 65 years and older with HIV in the USA were more likely to receive opioid prescriptions and have OUD indicators than matched beneficiaries without HIV. Findings could help guide clinical opioid prescription guidelines and public health surveillance among this vulnerable ageing population.

BACKGROUND: There is longstanding concern that people with HIV receive prescription opioids at higher rates and have a disproportionate burden of opioid use disorder (OUD) compared with their counterparts without HIV. We aimed to evaluate trends of opioid prescriptions and indicators of OUD in an understudied but growing population of older adults with HIV.

DETAILS: For this retrospective repeated cross-sectional study, authors constructed annual cohorts through a nationally representative sample of fee-for-service Medicare beneficiaries aged 65 years and older in the USA with Part D coverage (ie, prescription drug) enrolled between Jan 1, 2008, and Dec 31, 2021. Beneficiaries were eligible for inclusion in each cross-sectional cohort if they had reached the age of 65 years by Jan 1 of the calendar year and had 1 year of continuous Medicare enrolment in Part A (inpatient hospital care), B (outpatient care), and D. Beneficiaries with HIV were matched in a 1:3 ratio to beneficiaries without HIV on age, sex, race or ethnicity, US state, and dual eligibility status (Medicare and Medicaid). The main outcomes were receipt of at least one opioid prescription and any indicator of OUD (ie, formal diagnosis, medication for OUD, or opioid-related or emergency department visits) during each calendar year. Generalised estimating equations were used to estimate odds ratios (ORs) of each outcome, comparing matched beneficiaries with or without HIV. Due to data availability, our analysis of indicators of OUD was restricted to 2008-16. Across all years, 163,429 beneficiaries with HIV and 490,287 beneficiaries without HIV were included (475,516 [72.7%] were male, 178,200 [27.3%] were female; 305,776 [46.8%] were non-Hispanic White, 238,172 [36.4%] were Black [or African American], 84,128 [12.9%] were Hispanic, 8964 [1.4%] were Asian or Pacific Islander, and 16,676 [2.6%] were other races or ethnicities). During 2008-21, 57,373 (35.1%) of 163,429 people with HIV and 138,547 (28.3%) of 490,287 people without HIV received at least one opioid prescription. During 2008-16, 2408 (3.1%) of 76,637 people with HIV and 2831 (1.2%) of 229,911 people without HIV had any indicator of OUD. Across all analysed years, beneficiaries with HIV had significantly increased odds of receiving at least one opioid prescription (OR 1.38, 95% CI 1.36-1.39) and having indicators of OUD (2.61, 2.47-2.76) compared with their matched counterparts without HIV.

Copyright © The Author(s). Elsevier Ltd. All rights reserved.

Source: Shiau, S., Drago, F., Kinkade, C. W., et al. (2024). Prescription Opioid Use and Opioid Use Disorder Among Older Adults With HIV in the USA From 2008 to 2021: A Retrospective Repeated Cross-Sectional Study. The Lancet Primary Care. 2025; 1(3): 100017. Published: September, 2025. DOI: 10.1016/j.lanprc.2025.100017.

A Prospective Interventional Study

[Posted 29/Sep/2025]

AUDIENCE: General Surgery, Internal Medicine, Hematology

KEY FINDINGS: Curettage remains optimal for thick, hyperkeratotic SKs, enabling histopathological confirmation. The 532 nm laser, preferred subjectively for convenience, may suit small, non-hyperkeratotic lesions but warrants further validation. Propane-butane cryotherapy offers a cost-effective alternative. The discordance between patient preferences (prioritizing convenience) and clinical efficacy underscores the need for personalized treatment strategies balancing outcomes, tolerability, and cosmetic expectations.

BACKGROUND: Seborrheic keratosis (SK) is the most prevalent benign skin tumor associated with aging, posing esthetic concerns and potential discomfort. The rising demand for cosmetic interventions prompts the exploration of effective removal methods. This study compares three treatment modalities: curettage, 532 nm laser, and propane-butane cryotherapy.

DETAILS: A prospective interventional clinical study was conducted with 30 subjects, treating 123 SK using curettage, 532 nm laser, and propane-butane cryotherapy. Randomized allocation and evaluations at 0, 4, 8, and 12 weeks were employed. Objective measures included clearance rates (assessed by a dermatologist) and blinded cosmetic ratings by 125 observers. Subjective outcomes encompassed patient-reported pain (VAS), side effects, satisfaction, and preferences. Curettage achieved the highest clearance rate (87.5% vs. laser: 55%, cryotherapy: 50%; p < 0.01). However, patients perceived complete healing most frequently with laser (90% vs. curettage: 87%, cryotherapy: 53%). Despite lower efficacy, 67% favored laser for future treatments, valuing minimal bleeding and no dressings. Observers rated curettage's cosmetic outcomes superior (50% vs. laser: 22.5%). Laser caused the fewest side effects (mean 0.93/lesion) but highest pain (VAS: 4.62 vs. cryotherapy: 3.85). Cryotherapy showed efficacy comparable to laser (50% vs. 55%) but more adverse events.

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Source: Timmermann, V., Krengel, S., Mrowka, P,, et al. (2024). Practical Approaches for Seborrheic Keratosis Treatment: Curettage Versus 532-nm Lithium Borate Laser Versus Cryotherapy: A Prospective Interventional Study. Lasers in Surgery and Medicine. 2025; 57(7): 581-589. Published: September, 2025. DOI: 10.1002/lsm.70042.