Broadly neutralizing antibodies for HIV-1 prevention and therapy.

Despite immense progress in our ability to prevent and treat HIV-1 infection, HIV-1 remains an incurable disease and a highly efficacious HIV-1 vaccine is not yet available. Additional tools to prevent and treat HIV-1 are therefore necessary. The identification of potent and broadly neutralizing antibodies (bNAbs) against HIV-1 has revolutionized the field and may prove clinically useful. Significant advances have been made in identifying broader and more potent antibodies, characterizing antibodies in preclinical animal models, engineering antibodies to extend half-life and expand breadth and functionality, and evaluating the efficacy of single bNAbs and bNAb combinations in people with and without HIV-1. Here, we review recent progress in developing bNAbs for the prevention and treatment of HIV-1.

Assessment of the performance of the plasma separation card for HIV-1 viral load monitoring in South Africa.

Scaling up of newer innovations that address the limitations of the dried blood spot and the logistics of plasma monitoring is needed. We employed a multi-site, cross-sectional assessment of the plasma separation card (PSC) on blood specimens collected from all consenting adults, assenting young and pediatric patients living with HIV from 10 primary healthcare clinics in South Africa. Venous blood for EDTA-plasma samples was collected and analyzed according to the standard of care assay, while collected capillary blood for the PSC samples was analyzed using the Roche COBAS AmpliPrep/Cobas TaqMan (CAP/CTM) HIV-1 Test at the National Reference laboratories. McNemar tests assessed the differences in concordance between the centrifuged plasma and dried plasma spots. The usability of PSC by blood spotting, PSC preparation, and pre-analytical work was assessed by collecting seven-point Likert-scale data from healthcare and laboratory workers. We enrolled 538 patients, mostly adults [n = 515, 95.7% (95% CI: 93.7%-97.1%)] and females [n = 322, 64.2% (95% CI: 60.0%-68.1%)]. Overall, 536 paired samples were collected using both PSC- and EDTA-plasma diagnostics, and 502 paired PSC- and EDTA-plasma samples assessed. Concordance between the paired samples was obtained for 446 samples. Analysis of these 446 paired samples at 1,000 copies per milliliter threshold yielded an overall sensitivity of 87.5% [95% CI: 73.2%-95.8%] and specificity of 99.3% [95% CI: 97.9%-99.8%]. Laboratory staff reported technical difficulties in most tasks. The usability of the PSC by healthcare workers was favorable. For policymakers to consider PSC scale-up for viral load monitoring, technical challenges around using PSC at the clinic and laboratory level need to be addressed. IMPORTANCE: Findings from this manuscript emphasize the reliability of the plasma separation card (PSC), a novel diagnostic method that can be implemented in healthcare facilities in resource-constrained settings. The agreement of the PSC with the standard of care EDTA plasma for viral load monitoring is high. Since the findings showed that these tests were highly specific, we recommend a scale-up of PSC in South Africa for diagnosis of treatment failure.

Comparison between R2'-based and R2*-based χ-separation methods: A clinical evaluation in individuals with multiple sclerosis.

Susceptibility source separation, or χ-separation, estimates diamagnetic (χdia) and paramagnetic susceptibility (χpara) signals in the brain using local field and R2' (= R2* - R2) maps. Recently proposed R2*-based χ-separation methods allow for χ-separation using only multi-echo gradient echo (ME-GRE) data, eliminating the need for additional data acquisition for R2 mapping. Although this approach reduces scan time and enhances clinical utility, the impact of missing R2 information remains a subject of exploration. In this study, we evaluate the viability of two previously proposed R2*-based χ-separation methods as alternatives to their R2'-based counterparts: model-based R2*-χ-separation versus χ-separation and deep learning-based χ-sepnet-R2* versus χ-sepnet-R2'. Their performances are assessed in individuals with multiple sclerosis (MS), comparing them with their corresponding R2'-based counterparts (i.e., R2*-χ-separation vs. χ-separation and χ-sepnet-R2* vs. χ-sepnet-R2'). The evaluations encompass qualitative visual assessments by experienced neuroradiologists and quantitative analyses, including region of interest analyses and linear regression analyses. Qualitatively, R2*-χ-separation tends to report higher χpara and χdia values compared with χ-separation, leading to less distinct lesion contrasts, while χ-sepnet-R2* closely aligns with χ-sepnet-R2'. Quantitative analysis reveals a robust correlation between both R2*-based methods and their R2'-based counterparts (r ≥ 0.88). Specifically, in the whole-brain voxels, χ-sepnet-R2* exhibits higher correlation and better linearity than R2*-χ-separation (χdia/χpara from R2*-χ-separation: r = 0.88/0.90, slope = 0.79/0.86; χdia/χpara from χ-sepnet-R2*: r = 0.90/0.92, slope = 0.99/0.97). In MS lesions, both R2*-based methods display comparable correlation and linearity (χdia/χpara from R2*-χ-separation: r = 0.90/0.91, slope = 0.98/0.91; χdia/χpara from χ-sepnet-R2*: r = 0.88/0.88, slope = 0.91/0.95). Notably, χ-sepnet-R2* demonstrates negligible offsets, whereas R2*-χ-separation exhibits relatively large offsets (0.02 ppm in the whole brain and 0.01 ppm in the MS lesions), potentially indicating the false presence of myelin or iron in MS lesions. Overall, both R2*-based χ-separation methods demonstrated their viability as alternatives to their R2'-based counterparts. χ-sepnet-R2* showed better alignment with its R2'-based counterpart with minimal susceptibility offsets, compared with R2*-χ-separation that reported higher χpara and χdia values compared with R2'-based χ-separation.

Beyond lectures and practical courses: Teaching pharmacology using imaginative pedagogical tools.

Pharmacology has broadened its scope considerably in recent decades. Initially, it was of interest to chemists, doctors and pharmacists. In recent years, however, it has been incorporated into the teaching of biologists, molecular biologists, biotechnologists, chemical engineers and many health professionals, among others. Traditional teaching methods, such as lectures or laboratory work, have been superseded by the use of new pedagogical approaches to enable a better conceptualization and understanding of the discipline. In this article, we present several new methods that have been used in Spanish universities. Firstly, we describe a teaching network that has allowed the sharing of pedagogical innovations in Spanish universities. A European experience to improve prescribing safety is described in detail. The use of popular films and medical TV series in biomedical students shows how these audiovisual resources can be helpful in teaching pharmacology. The use of virtual worlds is detailed to introduce this new approach to teaching. The increasingly important area of the social aspects of pharmacology is also considered in two sections, one devoted to social pharmacology and the other to the use of learning based on social services to improve understanding of this important area. Finally, the use of Objective Structured Clinical Evaluation in pharmacology allows to know how this approach can help to better evaluate clinical pharmacology students. In conclusion, this article allows to know new pedagogical methods resources used in some Spanish universities that may help to improve the teaching of pharmacology.

Normal pressure hydrocephalus and cognitive impairment: The gait phenotype matters too.

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is a chronic neurological disease resulting in progressive gait and cognitive disorders. We investigated whether the gait phenotype is associated with the severity of cognitive deficits in iNPH. METHODS: This retrospective study recruited 88 patients (mean age = 76.18 ± 7.21 years, 42% female). Patients were initially referred for suspicion of iNPH and underwent a comprehensive analysis, including gait analysis and cognitive evaluation. RESULTS: In this cohort (27% normal gait, 25% frontal gait, 16% parkinsonian gait, 27% other gait abnormalities), patients with parkinsonian and frontal gait had the lowest Mini-Mental State Examination (MMSE) scores and the slowest gait speed. Patients with normal gait had the highest MMSE scores and gait speed. Frontal gait was associated with lower MMSE score, even after adjusting for age, gender, comorbidities, white matter lesions, and education level (ß = -0.221 [95% confidence interval (CI) = -3.718 to -0.150], p = 0.034). Normal gait was associated with the best MMSE scores, even after adjusting for the abovementioned variables (ß = 0.231 [95% CI = 0.124-3.639], p = 0.036). CONCLUSIONS: Gait phenotypes among iNPH patients are linked to global cognition as assessed with MMSE.

In vitro safety signals for potential clinical development of the anti-inflammatory pregnane X receptor agonist FKK6.

Based on the mimicry of microbial metabolites, functionalized indoles were demonstrated as the ligands and agonists of the pregnane X receptor (PXR). The lead indole, FKK6, displayed PXR-dependent protective effects in DSS-induced colitis in mice and in vitro cytokine-treated intestinal organoid cultures. Here, we report on the initial in vitro pharmacological profiling of FKK6. FKK6-PXR interactions were characterized by hydrogen-deuterium exchange mass spectrometry. Screening FKK6 against potential cellular off-targets (G protein-coupled receptors, steroid and nuclear receptors, ion channels, and xenobiotic membrane transporters) revealed high PXR selectivity. FKK6 has poor aqueous solubility but was highly soluble in simulated gastric and intestinal fluids. A large fraction of FKK6 was bound to plasma proteins and chemically stable in plasma. The partition coefficient of FKK6 was 2.70, and FKK6 moderately partitioned into red blood cells. In Caco2 cells, FKK6 displayed high permeability (A-B: 22.8 × 10-6 cm.s-1) and no active efflux. These data are indicative of essentially complete in vivo absorption of FKK6. The data from human liver microsomes indicated that FKK6 is rapidly metabolized by cytochromes P450 (t1/2 5 min), notably by CYP3A4. Two oxidized FKK6 derivatives, including DC73 (N6-oxide) and DC97 (C19-phenol), were detected, and these metabolites had 5-7 × lower potency as PXR agonists than FKK6. This implies that despite high intestinal absorption, FKK6 is rapidly eliminated by the liver, and its PXR effects are predicted to be predominantly in the intestines. In conclusion, the PXR ligand and agonist FKK6 has a suitable pharmacological profile supporting its potential preclinical development.

An optimized IgG-based B7-H3xCD3 bispecific antibody for treatment of gastrointestinal cancers.

T cell-based immunotherapy has revolutionized oncological treatment. However, many patients do not respond to treatment, and long-term remissions remain rare, particularly in gastrointestinal cancers like colorectal cancer (CRC). B7-H3 is overexpressed in multiple cancer entities including CRC on both tumor cells and tumor vasculature, the latter facilitating influx of effector cells into the tumor site upon therapeutic targeting. We generated a panel of T cell-recruiting B7-H3xCD3 bispecific antibodies (bsAbs) and show that targeting a membrane-proximal B7-H3 epitope allows for a 100-fold reduction of CD3 affinity. In vitro, our lead compound CC-3 showed superior tumor cell killing, T cell activation, proliferation, and memory formation, whereas undesired cytokine release was reduced. In vivo, CC-3 mediated potent antitumor activity in three independent models using immunocompromised mice adoptively transferred with human effector cells with regard to prevention of lung metastasis and flank tumor growth as well as elimination of large established tumors. Thus, fine-tuning of both target and CD3 affinities as well as binding epitopes allowed for the generation of a B7-H3xCD3 bsAbs with promising therapeutic activity. CC-3 is presently undergoing good manufacturing practice (GMP) production to enable evaluation in a clinical "first-in-human" study in CRC.

The correlation between dermoscopy and clinical and pathological tests in the evaluation of skin photoaging.

BACKGROUND: There are no standards for evaluating skin photoaging. Dermoscopy is a non-invasive detection method that might be useful for evaluating photoaging. OBJECTIVE: To assess the correlation between the dermoscopic evaluation of photoaging and clinical and pathological evaluations. METHODS: The age, clinical evaluation (Fitzpatrick classification, Glogau Photoaging Classification, and Chung's standardized image ruler), histopathology (Masson staining and MMP-1 immunohistochemistry), and dermoscopy (Hu's and Isik's) of 40 donor skin samples were analyzed statistically, and Spearman rank correlation analysis was performed. RESULTS: There was a robust correlation between the total Hu scores and Isik dermoscopy. The correlation of dermoscopy with histopathology was higher than that of clinical evaluation methods. There is a strong correlation between telangiectases and lentigo. Xerosis, superficial wrinkle, diffuse erythema, telangiectases, and reticular pigmentation were significantly correlated with the three clinical evaluation methods. Superficial wrinkles were correlated with Masson, MMP-1, various clinical indicators, and other dermoscopic items. CONCLUSION: There is a good correlation between dermoscopy and clinical and histopathological examination. Dermoscopy might help evaluate skin photoaging.

A paradigm shift?-On the ethics of medical large language models.

After a wave of breakthroughs in image-based medical diagnostics and risk prediction models, machine learning (ML) has turned into a normal science. However, prominent researchers are claiming that another paradigm shift in medical ML is imminent-due to most recent staggering successes of large language models-from single-purpose applications toward generalist models, driven by natural language. This article investigates the implications of this paradigm shift for the ethical debate. Focusing on issues like trust, transparency, threats of patient autonomy, responsibility issues in the collaboration of clinicians and ML models, fairness, and privacy, it will be argued that the main problems will be continuous with the current debate. However, due to functioning of large language models, the complexity of all these problems increases. In addition, the article discusses some profound challenges for the clinical evaluation of large language models and threats to the reproducibility and replicability of studies about large language models in medicine due to corporate interests.

Improved Resolution and Image Quality of Musculoskeletal Magnetic Resonance Imaging using Deep Learning-based Denoising Reconstruction: A Prospective Clinical Study.

OBJECTIVE: To prospectively evaluate a deep learning-based denoising reconstruction (DLR) for improved resolution and image quality in musculoskeletal (MSK) magnetic resonance imaging (MRI). METHODS: Images from 137 contrast-weighted sequences in 40 MSK patients were evaluated. Each sequence was performed twice, first with the routine parameters and reconstructed with a routine reconstruction filter (REF), then with higher resolution and reconstructed with DLR, and with three conventional reconstruction filters (NL2, GA43, GA53). The five reconstructions (REF, DLR, NL2, GA43, and GA53) were de-identified, randomized, and blindly reviewed by three MSK radiologists using eight scoring criteria and a forced ranking. Quantitative SNR, CNR, and structure's full width at half maximum (FWHM) for resolution assessment were measured and compared. To account for repeated measures, Generalized Estimating Equations (GEE) with Bonferroni adjustment was used to compare the reader's scores, SNR, CNR, and FWHM between DLR vs. NL2, GA43, GA53, and REF. RESULTS: Compared to the routine REF images, the resolution was improved by 47.61% with DLR from 0.39 ± 0.15 mm2 to 0.20 ± 0.06 mm2 (p < 0.001). Per-sequence average scan time was shortened by 7.93% with DLR from 165.58 ± 21.86 s to 152.45 ± 25.65 s (p < 0.001). Based on the average scores, DLR images were rated significantly higher in all image quality criteria and the forced ranking (p < 0.001). CONCLUSION: This prospective clinical evaluation demonstrated that DLR allows approximately two times finer resolution and improved image quality compared to the standard-of-care images.

Enhancing clinical skills in pediatric trainees: a comparative study of ChatGPT-assisted and traditional teaching methods.

BACKGROUND: As artificial intelligence (AI) increasingly integrates into medical education, its specific impact on the development of clinical skills among pediatric trainees needs detailed investigation. Pediatric training presents unique challenges which AI tools like ChatGPT may be well-suited to address. OBJECTIVE: This study evaluates the effectiveness of ChatGPT-assisted instruction versus traditional teaching methods on pediatric trainees' clinical skills performance. METHODS: A cohort of pediatric trainees (n = 77) was randomly assigned to two groups; one underwent ChatGPT-assisted training, while the other received conventional instruction over a period of two weeks. Performance was assessed using theoretical knowledge exams and Mini-Clinical Evaluation Exercises (Mini-CEX), with particular attention to professional conduct, clinical judgment, patient communication, and overall clinical skills. Trainees' acceptance and satisfaction with the AI-assisted method were evaluated through a structured survey. RESULTS: Both groups performed similarly in theoretical exams, indicating no significant difference (p > 0.05). However, the ChatGPT-assisted group showed a statistically significant improvement in Mini-CEX scores (p < 0.05), particularly in patient communication and clinical judgment. The AI-teaching approach received positive feedback from the majority of trainees, highlighting the perceived benefits in interactive learning and skill acquisition. CONCLUSION: ChatGPT-assisted instruction did not affect theoretical knowledge acquisition but did enhance practical clinical skills among pediatric trainees. The positive reception of the AI-based method suggests that it has the potential to complement and augment traditional training approaches in pediatric education. These promising results warrant further exploration into the broader applications of AI in medical education scenarios.

A Clinical, Pharmacological, and Formulation Evaluation of Melatonin in the Treatment of Ocular Disorders-A Systematic Review.

Melatonin's cytoprotective properties may have therapeutic implications in treating ocular diseases like glaucoma and age-related macular degeneration. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. This study aims to summarize the screened articles on melatonin's clinical, pharmacological, and formulation evaluation in treating ocular disorders. The identification of relevant studies on the topic in focus was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. The studies were searched in the following databases and web search engines: Pubmed, Scopus, Science Direct, Web of Science, Reaxys, Google Scholar, Google Patents, Espacenet, and Patentscope. The search time interval was 2013-2023, with the following keywords: melatonin AND ocular OR ophthalmic AND formulation OR insert AND disease. Our key conclusion was that using melatonin-loaded nano-delivery systems enabled the improved permeation of the molecule into intraocular tissues and assured controlled release profiles. Although preclinical studies have demonstrated the efficacy of developed formulations, a considerable gap has been observed in the clinical translation of the results. To overcome this failure, revising the preclinical experimental phase might be useful by selecting endpoints close to clinical ones.

ANTIFON-CLIC®, a new clinical decision support system for the treatment of invasive aspergillosis: is it clinically relevant?

BACKGROUND: Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients. PATIENTS AND METHODS: This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications. RESULTS: Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals. DISCUSSION: The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS. CONCLUSIONS: This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.

[Brief Analysis of Clinical Evaluation Concerns of Personalized Abutments and Abutment Crown Bridge Products].

Objective: The applications of personalized abutments and abutment crown bridge products have increased year by year, but there is no clear requirement for clinical evaluation of the same variety of such products. This study mainly introduces the clinical evaluation concerns of personalized abutments and abutment crown bridge products, in order to provide reference for the declaration and registration of such products. Methods: The clinical evaluation of personalized abutments and crown bridge products are summarized, and the research content of clinical evaluation is clarified. Results: The clinical evaluation requirements that need to be considered by enterprises are introduced. Conclusion: Personalized abutment and abutment crown bridge products can refer to this study when they are launched in China, mainly using in vitro performance comparison tests for equivalence verification.

Evaluation of belimumab in treatment of Chinese childhood-onset systemic lupus erythematosus: a prospective analysis from multicenter study.

OBJECTIVE: The aim of this study is to identify whether low lupus disease activity status (LLDAS) and clinical remission (CR) of belimumab plus standard of care (SoC) therapy are achievable goals in childhood-onset SLE (cSLE). METHODS: This multicentre, one arm pre-post intervention study was conducted at 15 centers in China. The primary end point was to describe the proportion of patients who achieved LLDAS and CR after 3, 6, and 12 months after treatment with belimumab plus SoC therapy. A multiple regression model was used to impute missing data. A Poisson regression model was used to calculate the effect of belimumab treatment on the reduced risk of serious diseases and the incidence of new damage. RESULT: 193 (92.2% female) with active cSLE from 15 centers were included. At 3, 6 and 12 months, the proportion of LLDAS (CR) was 12.4% (1.0%), 25.6% (4.5%) and 70.3% (29.7%), respectively. The mean SELENA-SLEDAI score decreased from 11.0 at baseline to 3.7, 2.9 and 1.7 at 3, 6, and 12 months. At baseline, all patients received steroids at a mean (SD) prednisone equivalent dose of 31.0 (18.2) mg/day, which decreased to 19.4 (10.8) mg/day at month 3, 12.6 (7.2) mg/day at month 6 and 6.7 (5.3) mg/day at month 12. The symptoms and immunological indicators were also significantly improved. CONCLUSION: This is the first and largest sample size prospective clinical intervention study of cSLE patients treated with belimumab in China. LLDAS and CR were attainable treat-to-target of belimumab plus SoC therapy in cSLE.

Clinical evaluation of a dermatophyte RT-PCR assay and its impact on the turn-around-time: A prospective study.

Onychomycosis is an important public health problem whose prevalence continues to grow and impact public health at several levels. Nevertheless, today the main diagnostic methods used in routine practice have many drawbacks. The aim of this study was to evaluate, for the first time, the clinical performance of a new multiplex polymerase chain reaction (PCR) (Novaplex®) in the identification of the causative agent on nail samples, and its impact on the turnaround time, compared to our traditional laboratory methods. From June 2022 to December 2022, all nail samples sent to our laboratory for suspected onychomycosis were included in this prospective study. We collected for each sample the results obtained with the Novaplex® PCR method and with the traditional direct microscopy examination and culture. Each discordant result was checked using a third method, which is another PCR method (DermaGenius® kit) as a resolver. For culture-positive samples, a turnaround time was calculated and compared to the one obtained with the Novaplex® method. A total of 131 samples were included. Among them, 5 were positive (3.8%) on direct microscopy, 33 were positive (25.2%) after culture, and 98 were negative (74.8%). All positive (n = 33) and negative (n = 69) cultures were also positive/negative with the Novaplex® PCR. Twenty-nine samples were positive with the Novaplex® method but negative with culture (discordant results). The percentage agreement between the culture and the Novaplex® methods was 77.9% (102 out of 131). While tested with the resolver (DermaGenius® PCR), 28 out of 29 discordant results were similarly found positive. The percentage agreement between the two PCR methods (Novaplex® and DermaGenius®) was 96.6%. The Novaplex® PCR method evaluated proved to be very reliable and allowed the direct identification of 62 out of 131 positive samples (47.3%) with the following distribution: 79.0% of Trichophyton rubrum complex, 11.3% of Trichophyton mentagrophytes complex, 6.5% of both Trichophyton rubrum complex and Trichophyton mentagrophytes complex, and 3.2% of Candida albicans. The median time [± 95% CI] for positive culture (between incubation and validation of the final identification) was 15 [12-23] days, while the turnaround time for the Novaplex® method adapted to our clinical laboratory routine is ≤7 days. Laboratory confirmation of onychomycosis is crucial and should always be obtained before starting treatment. The evaluated PCR method offered a rapid, reliable, robust, and inexpensive method of identification of the causative agent compared to traditional methods.

The aim of this study was to evaluate the clinical performance of a multiplex PCR in the identification of the causative agent of onychomycosis on nail samples, and its impact on the turnaround time, compared to our traditional laboratory methods. This new method is rapid, reliable, robust, and inexpensive.

In vivo evaluation of a hyperspectral imaging system for minimally invasive surgery (HSI-MIS).

BACKGROUND: Hyperspectral Imaging (HSI) is a reliable and safe imaging method for taking intraoperative perfusion measurements. This is the first study translating intraoperative HSI to an in vivo laparoscopic setting using a CE-certified HSI-system for minimally invasive surgery (HSI-MIS). We aim to compare it to an established HSI-system for open surgery (HSI-Open). METHODS: Intraoperative HSI was done using the HSI-MIS and HSI-Open at the Region of Interest (ROI). 19 patients undergoing gastrointestinal resections were analyzed in this study. The HSI-MIS-acquired images were aligned with those from the HSI-Open, and spectra and parameter images were compared pixel-wise. We calculated the Mean Absolute Error (MAE) for Tissue Oxygen Saturation (StO2), Near-Infrared Perfusion Index (NIR-PI), Tissue Water Index (TWI), and Organ Hemoglobin Index (OHI), as well as the Root Mean Squared Error (RMSE) over the whole spectrum. Our analysis of parameters was optimized using partial least squares (PLS) regression. Two experienced surgeons carried out an additional color-change analysis, comparing the ROI images and deciding whether they provided the same (acceptable) or different visual information (rejected). RESULTS: HSI and subsequent image registration was possible in 19 patients. MAE results for the original calculation were StO2 orig. 17.2% (± 7.7%), NIR-PIorig. 16.0 (± 9.5), TWIorig. 18.1 (± 7.9), OHIorig. 14.4 (± 4.5). For the PLS calculation, they were StO2 PLS 12.6% (± 5.2%), NIR-PIPLS 10.3 (± 6.0), TWIPLS 10.6 (± 5.1), and OHIPLS 11.6 (± 3.0). The RMSE between both systems was 0.14 (± 0.06). In the color-change analysis; both surgeons accepted more images generated using the PLS method. CONCLUSION: Intraoperative HSI-MIS is a new technology and holds great potential for future applications in surgery. Parameter deviations are attributable to technical differences and can be reduced by applying improved calculation methods. This study is an important step toward the clinical implementation of HSI for minimally invasive surgery.

Intra-abdominal laparoscopic assessment of organs perfusion using imaging photoplethysmography.

BACKGROUND: An objective evaluation of the functional state and viability of biological tissues during minimally invasive surgery remains unsolved task. Various non-contact methods for evaluating perfusion during laparoscopic surgery are discussed in the literature, but so far there have been no reports of their use in clinical settings. METHODS AND PATIENTS: Imaging photoplethysmography (iPPG) is a new method for quantitative assessment of perfusion distribution along the tissue. This is the first study in which we demonstrate successful use of iPPG to assess perfusion of organs during laparoscopic surgery in an operation theater. We used a standard rigid laparoscope connected to a standard digital monochrome camera, and abdominal organs were illuminated by green light. A distinctive feature is the synchronous recording of video frames and electrocardiogram with subsequent correlation data processing. During the laparoscopically assisted surgeries in nine cancer patients, the gradient of perfusion of the affected organs was evaluated. In particular, measurements were carried out before preparing a part of the intestine or stomach for resection, after anastomosis, or during physiological tests. RESULTS: The spatial distribution of perfusion and its changes over time were successfully measured in all surgical cases. In particular, perfusion gradient of an intestine before resection was visualized and quantified by our iPPG laparoscope in all respective cases. It was also demonstrated that systemic administration of norepinephrine leads to a sharper gradient between well and poorly perfused areas of the colon. In four surgical cases, we have shown capability of the laparoscopic iPPG system for intra-abdominal assessment of perfusion in the anastomosed organs. Moreover, good repeatability of continuous long-term measurements of tissue perfusion inside the abdominal cavity was experimentally demonstrated. CONCLUSION: Our study carried out in real clinical settings has shown that iPPG laparoscope is feasible for intra-abdominal visualization and quantitative assessment of perfusion distribution.

International Urogynecology consultation chapter 2 committee 3: the clinical evaluation of pelvic organ prolapse including investigations into associated morbidity/pelvic floor dysfunction.

INTRODUCTION AND HYPOTHESIS: This manuscript from Chapter 2 of the International Urogynecology Consultation (IUC) on Pelvic Organ Prolapse (POP) reviews the literature involving the clinical evaluation of a patient with POP and associated bladder and bowel dysfunction. METHODS: An international group of 11 clinicians performed a search of the literature using pre-specified search MESH terms in PubMed and Embase databases (January 2000 to August 2020). Publications were eliminated if not relevant to the clinical evaluation of patients or did not include clear definitions of POP. The titles and abstracts were reviewed using the Covidence database to determine whether they met the inclusion criteria. The manuscripts were reviewed for suitability using the Specialist Unit for Review Evidence checklists. The data from full-text manuscripts were extracted and then reviewed. RESULTS: The search strategy found 11,242 abstracts, of which 220 articles were used to inform this narrative review. The main themes of this manuscript were the clinical examination, and the evaluation of comorbid conditions including the urinary tract (LUTS), gastrointestinal tract (GIT), pain, and sexual function. The physical examination of patients with pelvic organ prolapse (POP) should include a reproducible method of describing and quantifying the degree of POP and only the Pelvic Organ Quantification (POP-Q) system or the Simplified Pelvic Organ Prolapse Quantification (S-POP) system have enough reproducibility to be recommended. POP examination should be done with an empty bladder and patients can be supine but should be upright if the prolapse cannot be reproduced. No other parameters of the examination aid in describing and quantifying POP. Post-void residual urine volume >100 ml is commonly used to assess for voiding difficulty. Prolapse reduction can be used to predict the possibility of postoperative persistence of voiding difficulty. There is no benefit of urodynamic testing for assessment of detrusor overactivity as it does not change the management. In women with POP and stress urinary incontinence (SUI), the cough stress test should be performed with a bladder volume of at least 200 ml and with the prolapse reduced either with a speculum or by a pessary. The urodynamic assessment only changes management when SUI and voiding dysfunction co-exist. Demonstration of preoperative occult SUI has a positive predictive value for de novo SUI of 40% but most useful is its absence, which has a negative predictive value of 91%. The routine addition of radiographic or physiological testing of the GIT currently has no additional value for a physical examination. In subjects with GIT symptoms further radiological but not physiological testing appears to aid in diagnosing enteroceles, sigmoidoceles, and intussusception, but there are no data on how this affects outcomes. There were no articles in the search on the evaluation of the co-morbid conditions of pain or sexual dysfunction in women with POP. CONCLUSIONS: The clinical pelvic examination remains the central tool for evaluation of POP and a system such as the POP-Q or S-POP should be used to describe and quantify. The value of investigation for urinary tract dysfunction was discussed and findings presented. The routine addition of GI radiographic or physiological testing is currently not recommended. There are no data on the role of the routine assessment of pain or sexual function, and this area needs more study. Imaging studies alone cannot replace clinical examination for the assessment of POP.

A Review on Penile Doppler and Ultrasonography for Erectile Dysfunction.

PURPOSE OF REVIEW: Herein, we seek to review the clinical applications of penile duplex Doppler ultrasound (PDDU) in sexual medicine practices and discuss the indications, protocols, advantages, and limitations of this diagnostic modality. Other more outdated diagnostic tests, such as cavernosometry, are briefly discussed to provide the reader a background of understanding on the evolution of diagnostic testing within the realm of sexual medicine. RECENT FINDINGS: PDDU has become a key diagnostic tool in the clinical evaluation of both erectile dysfunction (ED) and Peyronie's disease (PD). With the assistance of intracavernosal injections such as alprostadil, clinicians can utilize ultrasound technology to produce a detailed description of the hemodynamics of the patient's erection cycle. This information plays a pivotal role in establishing an accurate diagnosis and creating a sensible management plan for the patient. This review aims to provide a better understanding regarding the technique and interpretation of PDDU as it pertains to male sexual function.