Comparison of topical permethrin 5% vs. benzyl benzoate 25% treatment in scabies: a double-blinded randomized controlled trial.

BACKGROUND: Scabies is a pruritic parasitic infestation of the skin. High-income countries have reported an increasing incidence over the last few years. Studies have indicated a reduction in the sensitivity of scabies mites to the standard treatment of choice, topical permethrin 5%. OBJECTIVES: To evaluate in a head-to-head manner the efficacy of two topical scabicides [permethrin 5% and benzyl benzoate 25% (BB)] in the treatment of scabies using the same administration modality; and to address potential confounding factors such as incorrectly performed treatment and hygiene measures. METHODS: In total, 110 patients with dermoscopy-verified scabies infestation were enrolled and randomized into two equally sized groups in a double-blinded manner. Fifty-five received topical permethrin 5% and 55 received topical BB 25%, both for daily use over a period of three consecutive days. Treatment outcome was evaluated by dermoscopy at a 3-week follow-up visit. RESULTS: Treatment resulted in a dermoscopy-verified cure rate of 27% in the permethrin group and 87% in the BB group. The tolerability and safety profile of permethrin 5% cream was excellent, while the BB emulsion produced a burning sensation in 43% of patients. CONCLUSIONS: Topical permethrin demonstrated a lack of efficacy in the majority of scabies cases, whereas BB demonstrated an excellent cure rate and reasonable tolerability. Considering the reduced sensitivity of scabies mites to permethrin 5%, our results suggest that BB is an appropriate first-line therapy in the treatment of scabies.

Outcomes of rectal cancer patients who refuse surgery after incomplete clinical response to neoadjuvant therapy.

BACKGROUND AND OBJECTIVES: Total mesorectal excision (TME) remains the standard of care for patients with rectal cancer who have an incomplete response to total neoadjuvant therapy (TNT). A minority of patients will refuse curative intent resection. The aim of this study is to examine the outcomes for these patients. METHODS: A retrospective cohort study of stage 1-3 rectal adenocarcinoma patients who underwent neoadjuvant chemoradiation therapy or TNT at a single institution. Patients either underwent TME, watch-and-wait protocol, or if they refused TME, were counseled and watched (RCW). Clinical outcomes and resource utilization were examined in each group. RESULTS: One hundred seventy-one patients (Male 59%) were included with a median surveillance of 43 months. Twenty-nine patients (17%) refused TME and had shortened overall survival (OS). Twelve patients who refused TME converted to a complete clinical response (cCR) on subsequent staging with a prolonged OS. 92% of these patients had a near cCR at initial staging endoscopy. Increased physician visits and testing was utilized in RCW and WW groups. CONCLUSION: A significant portion of patients convert to cCR and have prolonged OS. Lengthening the time to declare cCR may be considered in select patients, such as those with a near cCR at initial endoscopic staging.

The performance of artificial intelligence large language model-linked chatbots in surgical decision-making for gastroesophageal reflux disease.

BACKGROUND: Large language model (LLM)-linked chatbots may be an efficient source of clinical recommendations for healthcare providers and patients. This study evaluated the performance of LLM-linked chatbots in providing recommendations for the surgical management of gastroesophageal reflux disease (GERD). METHODS: Nine patient cases were created based on key questions addressed by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines for the surgical treatment of GERD. ChatGPT-3.5, ChatGPT-4, Copilot, Google Bard, and Perplexity AI were queried on November 16th, 2023, for recommendations regarding the surgical management of GERD. Accurate chatbot performance was defined as the number of responses aligning with SAGES guideline recommendations. Outcomes were reported with counts and percentages. RESULTS: Surgeons were given accurate recommendations for the surgical management of GERD in an adult patient for 5/7 (71.4%) KQs by ChatGPT-4, 3/7 (42.9%) KQs by Copilot, 6/7 (85.7%) KQs by Google Bard, and 3/7 (42.9%) KQs by Perplexity according to the SAGES guidelines. Patients were given accurate recommendations for 3/5 (60.0%) KQs by ChatGPT-4, 2/5 (40.0%) KQs by Copilot, 4/5 (80.0%) KQs by Google Bard, and 1/5 (20.0%) KQs by Perplexity, respectively. In a pediatric patient, surgeons were given accurate recommendations for 2/3 (66.7%) KQs by ChatGPT-4, 3/3 (100.0%) KQs by Copilot, 3/3 (100.0%) KQs by Google Bard, and 2/3 (66.7%) KQs by Perplexity. Patients were given appropriate guidance for 2/2 (100.0%) KQs by ChatGPT-4, 2/2 (100.0%) KQs by Copilot, 1/2 (50.0%) KQs by Google Bard, and 1/2 (50.0%) KQs by Perplexity. CONCLUSIONS: Gastrointestinal surgeons, gastroenterologists, and patients should recognize both the promise and pitfalls of LLM's when utilized for advice on surgical management of GERD. Additional training of LLM's using evidence-based health information is needed.

Colloidal Stabilization of Submicron-Sized Zeolite NaA in Ethanol-Water Mixtures for Nanostructuring into Thin Films and Nanofibers.

Despite the growing use of organic or mixed solvents in zeolite processing, most studies focus only on aqueous suspension systems. We investigated the colloidal characteristics of submicron-sized zeolite NaA in mixed ethanol-water solvents. The effects of the mixing ratio of solvents and various additives on the dispersion of the zeolite powders were studied. The zeolite NaA particles were destabilized in solvent mixtures at a high ethanol-to-water ratio, a reduction in the zeta potential was observed, and the destabilization was rationalized by the Derjaguin, Landau, Verwey, Overbeek (DLVO) theory. An improved stabilization of the zeolite NaA suspensions was achieved in ethanol-rich solvent mixtures using nonionic low molecular weight organic additives, but not with their ionic counterparts such as anionic, cationic surfactants or inorganic acids or bases. Polyethylene glycol (PEG)-400 was found to be a good dispersant for the submicron-sized zeolite NaA particles in the ethanol-water mixtures, which was attributed to its interaction with the zeolite surface, leading to an increased zeta potential. The PEG-stabilized zeolite suspensions led to low suspension viscosities as well as uniform and consistent spin-coated films.

Combined Liver and Colon Resection of Synchronous Colorectal Liver Metastases at a Quaternary Center.

INTRODUCTION: Existing literature on the safety of combined liver and colorectal resections for synchronous colorectal liver metastases is mixed. Using a retrospective review of our institutional data, we aimed to show that combined colorectal and liver resections for synchronous metastases is both feasible and safe in a quaternary center. METHODS: A retrospective review of combined resections for synchronous colorectal liver metastases at a quaternary referral center from 2015 to 2020 was completed. Clinicopathologic and perioperative data was collected. Univariate and multivariable analyses were performed to identify risk factors for major postoperative complications. RESULTS: One hundred one patients were identified, with 35 undergoing major liver resections ( ≥ 3 segments) and 66 undergoing minor liver resections. The vast majority of patients (94%) received neoadjuvant therapy. There was no difference in postoperative major complications (Clavien-Dindo grade 3+) between major and minor liver resections (23.9% versus 12.1%, P = 0.16). On univariate analysis, Albumin-Bilirubin (ALBI) score >1 (P < 0.05) was predictive of major complication. However, on multivariable regression analysis, no factor was associated with significantly increased odds of major complication. CONCLUSIONS: This work demonstrates that with thoughtful patient selection, combined resection for synchronous colorectal liver metastases can be safely performed at a quaternary referral center.

Tumor extent impacts survival benefit in minimally invasive colectomy for T4 colon cancer: A propensity matched national cohort analysis.

BACKGROUND: T4 colon cancers have been underrepresented in randomized trials comparing minimally invasive colectomy (MC) versus open colectomy (OC). Retrospective studies suggest improved survival with MC versus OC, but have not addressed the impact of tumor extent. METHODS: Using the National Cancer Database (NCDB), we analyzed patients undergoing colectomy for T4 colon adenocarcinoma from 2010 to 2014. Propensity score matching was performed between MC and OC patients. Tumor extent was defined by zones based on adjacent organ involvement. RESULTS: Of the 19 178 eligible patients, 6564 (34%) underwent MC. After matching, MC was associated with improved overall survival (hazard ratios: 0.71, 95% confidence interval: 0.67-0.76; median OS 59 vs. 42 months, p < 0.001). Compared to MC patients, those undergoing OC had: a higher margin positive rate (p = 0.009); lower median nodes examined (p < 0.001); a lower rate of adjuvant chemotherapy (p < 0.001); and a longer median time to chemotherapy (p < 0.001). Stratified survival analyses demonstrated that MC was associated with improved overall survival compared to OC in all zones except zone 3 and 4. CONCLUSIONS: Compared to OC, MC for T4 colon cancer is associated with improved oncologic outcomes when performed for zone 0-2 tumors. For, zone 3 and 4 tumors MC and OC have similar oncologic outcomes and patients should be cautiously selected.

Feasibility of perioperative remote monitoring of patient-generated health data in complex surgical oncology.

BACKGROUND: The feasibility of remote perioperative telemonitoring of patient-generated physiologic health data and patient-reported outcomes in a high risk complex general and urologic oncology surgery population is evaluated. METHODS: Complex general surgical/urologic oncology patients wore a pedometer, completed ePROs (electronic patient-reported outcome surveys) and record their vitals (weight, pulse, pulse oximetry, blood pressure, and temperature) via a telehealth app platform. Feasibility (% adherence) was assessed as the primary outcome measure. RESULTS: Twenty-one patients with a median age 58 (32-82) years were included. The readmission rate was 33% and the incidence of ≥Grade 3a morbidity was 24%. Adherence to vital sign and ePRO measurements was 95% before surgery, 91% at discharge, and 82%, 68%, and 64% at postdischarge d2, 7, 14, and 30, respectively. There was significant worsening of mobility, self-care and usual daily activity at postdischarge d2 compared to preoperative baseline (p < 0.05). Median daily preoperative steps taken by patients with

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS).

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are of public health concern, because of their ubiquitous and extremely persistent occurrence, and depending on their structure, their bio-accumulative, mobile and toxic properties. Human health effects associated with exposure to PFAS include adverse effects on the immune system. In 2020, EFSA (the European Food Safety Authority) defined adverse effects on the immune system as the most critical effect for human health risk assessment, based on reduced antibody responses to childhood vaccines and similar effects observed in experimental animal studies. Likewise, the U.S. EPA (Environmental Protection Agency) considers PFAS-induced immunotoxicity, especially in children, as the critical effect for risk assessment. However, the mechanisms by which antibody concentrations are impacted are not completely understood. Furthermore, other targets of the immune system functions have been reported in the literature. OBJECTIVE: The aim of this review is to explore PFAS-associated immune-related effects. This includes, relevant mechanisms that may underlie the observed effects on the immune system, immunosuppression as well as immunoenhancement, such as i) modulation of cell signalling and nuclear receptors, such as NF-κB and PPARs; ii) alteration of calcium signalling and homoeostasis in immune cells; iii) modulation of immune cell populations; iv) oxidative stress and v) impact on fatty acid metabolism & secondary effects on the immune system. METHODS: A literature research was conducted using three databases (Web of Science, PubMed, and Scopus), which were searched in July 2021 for relevant studies published in the time frame from 2018 to 2021. In total, 487 publications were identified as potentially eligible and following expert-based judgement, articles relevant for mechanisms of PFAS induced immunotoxicity are discussed. CONCLUSIONS: Taken together, we show that there is substantial evidence from both in vitro and in vivo experimental as well as epidemiological studies, supporting that various PFAS, not only PFOA and PFOS, affect multiple aspects of the immune system. Timing of exposure is critical, because the developing immune system is especially vulnerable to toxic insults, resulting in a higher risk of particularly adverse immune effects but also other organs later in life.

The SAGES MASTERS program presents: the top 10 seminal articles for laparoscopic left and sigmoid colectomy pathway for uncomplicated disease.

BACKGROUND: As one of the 8 Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program clinical pathways, the Colorectal Pathway aims to deliver educational content for the general surgeon organized along 3 levels of performance (competency, proficiency and mastery) each represented by an anchoring procedure. In this article, the SAGES Colorectal Task Force presents focused summaries of the top 10 seminal articles selected for laparoscopic left/sigmoid colectomy for uncomplicated disease. METHODS: Using a systematic literature search of Web of Science, the most cited articles on laparoscopic left and sigmoid colectomy were identified, reviewed, and ranked by members of the SAGES Colorectal Task Force. Additional articles not identified in the literature search were included if deemed impactful by expert consensus. The top 10 ranked articles were then summarized, including their findings, strengths and limitations with emphasis on relevance and impact in the field. RESULTS: The top 10 articles selected focus on variations in minimally invasive surgical techniques, video demonstrations, stratified approaches for benign and malignant disease as well as assessments of the learning curve. CONCLUSIONS: The selected top 10 seminal articles for laparoscopic left and sigmoid colectomy in uncomplicated disease are considered by the SAGES colorectal task force to be fundamental to the knowledge base of minimally invasive surgeons as they progress to mastery in these procedures.

EAES, SAGES, and ESCP rapid guideline: bowel preparation for minimally invasive colorectal resection.

BACKGROUND: Variation exists in practice pertaining to bowel preparation before minimally invasive colorectal surgery. A survey of EAES members prioritized this topic to be addressed by a clinical practice guideline. OBJECTIVE: The aim of the study was to develop evidence-informed clinical practice recommendations on the use of bowel preparation before minimally invasive colorectal surgery, through evidence synthesis and a structured evidence-to-decision framework by an interdisciplinary panel of stakeholders. METHODS: This is a collaborative project of EAES, SAGES, and ESCP. We updated a previous systematic review and performed a network meta-analysis of interventions. We appraised the certainty of the evidence for each comparison, using the GRADE and CINeMA methods. A panel of general and colorectal surgeons, infectious diseases specialists, an anesthetist, and a patient representative discussed the evidence in the context of benefits and harms, the certainty of the evidence, acceptability, feasibility, equity, cost, and use of resources, moderated by a GIN-certified master guideline developer and chair. We developed the recommendations in a consensus meeting, followed by a modified Delphi survey. RESULTS: The panel suggests either oral antibiotics alone prior to minimally invasive right colon resection or mechanical bowel preparation (MBP) plus oral antibiotics; MBP plus oral antibiotics prior to minimally invasive left colon and sigmoid resection, and prior to minimally invasive right colon resection when there is an intention to perform intracorporeal anastomosis; and MBP plus oral antibiotics plus enema prior to minimally invasive rectal surgery (conditional recommendations); and recommends MBP plus oral antibiotics prior to minimally invasive colorectal surgery, when there is an intention to localize the lesion intraoperatively (strong recommendation). The full guideline with user-friendly decision aids is available in https://app.magicapp.org/#/guideline/LwvKej . CONCLUSION: This guideline provides recommendations on bowel preparation prior to minimally invasive colorectal surgery for different procedures, using highest methodological standards, through a structured framework informed by key stakeholders. Guideline registration number PREPARE-2023CN045.

Comparison of topical benzyl benzoate vs. oral ivermectin in treating scabies: A randomized study.

BACKGROUND: Scabies is an itchy, parasitic infection of the skin. Recent reports indicate there is a decreasing efficacy of the standard treatment of choice, topical 5% permethrin cream. OBJECTIVE: To evaluate the comparative efficacy, safety and tolerability of topical benzyl benzoate (BB) with oral ivermectin in the treatment of scabies. METHODS: Patients with dermoscopy-verified scabies visiting the dermatologic outpatient clinic were assessed for enrolment in the study. In total, 224 patients were enrolled and sequentially randomized into two equally sized groups. Group A received topical 25% or 10% BB for the daily use over a period of three consecutive days, group B received oral ivermectin (200 µg/kg body weight) twice, 1 week apart. Treatment outcome was evaluated by dermoscopy at a 3-week follow-up visit. RESULTS: Treatment resulted in a cure rate of 87% in group A and 86% in group B. After initial therapy failure in group A, six out of eight patients showed treatment response upon repeated application of BB, five of five when retreated with ivermectin and two of two with BB plus ivermectin, respectively. In group B, successful retreatment was observed in three out of three patients with ivermectin, two of two patients with BB and 11 of 11 patients with the combination of BB plus ivermectin, respectively. Tolerability and safety profile of oral ivermectin was excellent, while BB produced short burning sensations in 14%. CONCLUSION: Topical BB and oral ivermectin have shown comparable good therapeutic efficacy. Therefore, both agents constitute an adequate first-line therapy in the treatment of scabies. A combination of both agents may be considered in recalcitrant and extensively infested cases, additionally to crusted scabies.

Prenatal exposure to per- and polyfluoroalkyl substances and pregnancy outcome in Austria.

Per- and polyfluoroalkyl substances (PFAS) are a large group of persistent industrial chemicals that can harm reproductive health. PFAS levels were analysed to determine the current sources of exposure and possible associations between prenatal PFAS exposure and adverse pregnancy outcome. Samples from 136 mother-newborn pairs recruited between 2017 and 2019 were analysed for the presence of 31 target PFAS in maternal serum, umbilical cord serum, and placental tissue by high-performance liquid chromatography coupled to a tandem mass spectrometer. Questionnaires and medical records were used to survey sources of exposure and pregnancy outcome, including small for gestational age (SGA), fetal growth restriction (FGR), preeclampsia (PE), preterm birth, large for gestational age (LGA) and gestational diabetes mellitus (GDM). Data were analysed for individual PFAS and sum4PFAS (sum of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) serum levels) in logistic regression analyses and categorical regression analyses. Compared to data from a previous Viennese study in 2010-12, sum4PFAS levels were generally lower. Sum4PFAS serum levels of three women (2.2%) exceeded 6.9 µg/L, a level that corresponds to the recently established tolerable weekly intake (TWI) of EFSA for nursing mothers aged 35 years; in the 2010/2012 study it was 13.6%. The large contribution of unidentified extractable organofluorine (EOF) fractions to total PFAS exposure is a concern. Study site, mean maternal corpuscular hemoglobin (MCH), use of facial lotion, and owning upholstered furniture were significantly influencing maternal exposure. While no effect of sum4PFAS on pregnancy outcome could be detected, we found highest placental PFDA levels in SGA births. PFHxS levels in umbilical cord and placenta were highest in preterm births. Further studies are needed to elucidate the relationship of prenatal PFAS exposure and pregnancy outcome, in particular to confirm whether and how placental PFDA levels may contribute to an increased risk for SGA.

Electrospun aluminum silicate nanofibers as novel support material for immobilization of alcohol dehydrogenase.

Ceramic materials with high surface area, large and open porosity are considered excellent supports for enzyme immobilization owing to their stability and reusability. The present study reports the electrospinning of aluminum silicate nanofiber supports from sol-gel precursors, the impact of different fabrication parameters on the microstructure of the nanofibers and their performance in enzyme immobilization. A change in nanofiber diameter and pore size of the aluminum silicate nanofibers was observed upon varying specific processing parameters, such as the sol-composition (precursor and polymer concentration), the electrospinning parameters and the subsequent heat treatment (calcination temperature). The enzyme, alcohol dehydrogenase (ADH), was immobilized on the aluminum silicate nanofibers by physical adsorption and covalent bonding. Activity retention of 17% and 42% was obtained after 12 d of storage and repeated reaction cycles for physically adsorbed and covalently bonded ADH, respectively. Overall, the immobilization of ADH on aluminum silicate nanofibers resulted in high enzyme loading and activity retention. However, as compared to covalent immobilization, a marked decrease in the enzyme activity during storage for physically adsorbed enzymes was observed, which was ascribed to leakage of the enzymes from the nanofibers. Such fibers can improve enzyme stability and promote a higher residual activity of the immobilized enzyme as compared to the free enzyme. The results shown in this study thus suggest that aluminum silicate nanofibers, with their high surface area, are promising support materials for the immobilization of enzymes.

Extractable Organofluorine Analysis in Pooled Human Serum and Placental Tissue Samples from an Austrian Subpopulation-A Mass Balance Analysis Approach.

Embryos and fetuses are of major concern due to their high vulnerability. Previous studies demonstrated that human exposure to per- and polyfluoroalkyl substances (PFAS) may be underestimated because only a limited number of known PFAS can be measured. This investigation studied the total PFAS exposure by measuring the extractable organofluorine (EOF) in pooled maternal serum, placental tissue, and cord serum samples (total number of pooled samples: n = 45). The EOF was analyzed using combustion ion chromatography, and the concentrations of known PFAS were determined using ultraperformance liquid chromatography coupled with a tandem mass spectrometer. Using a mass balance analysis approach, the amount of unknown PFAS was estimated between the levels of known PFAS and EOF. The EOF levels ranged from 2.85 to 7.17 ng F/mL (21 PFAS were quantified) in the maternal serum, from 1.02 to 1.85 ng F/g (23 PFAS were quantified) in the placental tissue, and from 1.2 to 2.10 ng F/mL (18 PFAS were quantified) in the cord serum. An average of 24, 51, and 9% of EOF is unidentified in the maternal serum, placental tissue, and cord serum, respectively. The results show that the levels of unidentified EOF are higher in the placental tissue, suggesting accumulation or potential transformation of precursors in the placenta.

Comparison of extraction methods for per- and polyfluoroalkyl substances (PFAS) in human serum and placenta samples-insights into extractable organic fluorine (EOF).

Since the detection of per- and polyfluoroalkyl substances (PFAS) in humans and different environmental media in the last two decades, this substance group has attracted a lot of attention as well as increasing concerns. The fluorine mass balance approach, by comparing the levels of targeted PFAS after conversion to fluorine equivalents with those of extractable organic fluorine (EOF), showed the presence of unidentified organofluorine in different environmental samples. Out of the thousands of PFAS in existence, only a very small fraction is included in routine analysis. In recent years, liquid chromatography coupled with tandem-mass spectrometry (LC-MS/MS) has demonstrated the ability to analytically cover a wide spectrum of PFAS. In contrast, conventional extraction methods developed 10 to 15 years ago were only evaluated for a limited number of PFAS. The aim of the present study was to evaluate the advantages and disadvantages of three different extraction methods, adapted from the literatures without further optimization (ion-pair liquid-liquid extraction, solid-phase extraction (SPE), using hydrophilic-lipophilic (HLB) or weak anion exchange (WAX) sorbents), for human biomonitoring of 61 PFAS in serum and placental tissue samples. In addition, levels of EOF were compared among these extraction methods via spiked samples. Results showed that performance, in terms of recovery, differed between the extraction methods for different PFAS; different extraction methods resulted in different EOF concentrations indicating that the choice of extraction method is important for target PFAS and EOF analysis. Results of maternal serum samples, analyzed in two different laboratories using two different extraction methods, showed an accordance of 107.6% (± 21.3); the detected perfluoroalkyl acids (PFAAs) in maternal and cord serum samples were in the range of 0.076 to 2.9 ng/mL.Graphical abstract.

Ozone as oxidizing agent for the total oxidizable precursor (TOP) assay and as a preceding step for activated carbon treatments concerning per- and polyfluoroalkyl substance removal.

Several thousands of highly persistent per- and polyfluoroalkyl substances (PFAS) exist and it is therefore challenging to analytically determine a larger spectrum of these compounds simultaneously in one sample. It is even more difficult to efficiently remove mobile PFAS in wastewater treatment plants (WWTPs) to protect the receiving waters. The total oxidizable precursor (TOP) assay is an approach that enables the detection of the total PFAS content in a sample via oxidation of precursors, followed by subsequent analysis of the perfluoroalkyl acid (PFAA) concentration before and after oxidative processes. Activated carbon combined with a preceding ozonation step is considered a promising tool for the removal of micropollutants but considering PFAS removal efficiencies in effluents for this process combination more information is required. The focus of the study was to implement and assess the TOP assay with ozone as oxidizing agent to estimate the total PFAS content in a WWTP effluent. Additionally, granular activated carbon (GAC) and powdered activated carbon (PAC) with a preceding ozonation step was tested for the removal efficiencies for 22 PFAS. For the TOP assay the obtained accordance in molarity using spiked tap water as quality control was 95.2% (15 mg O3/L) and 99.1% (6 mg O3/L). Applying the TOP assay, an estimated total PFAS content of 840 ng/L was determined in the respective effluent, which was 91.1% higher than obtained by target PFAS analysis, implying the presence of unknown precursors not included in common monitoring. While all treatment techniques that included ozone or a preceding ozonation step solely transformed precursors and long-chain perfluoroalkyl acids (PFAA, i.e., >C9) to shorter congeners, PAC was the only tested water treatment application that was able to remove 19.3% of the total PFAS molarity.

Management Considerations for the Surgical Treatment of Colorectal Cancer During the Global Covid-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic requires to conscientiously weigh "timely surgical intervention" for colorectal cancer against efforts to conserve hospital resources and protect patients and health care providers. SUMMARY BACKGROUND DATA: Professional societies provided ad-hoc guidance at the outset of the COVID-19 pandemic on deferral of surgical and perioperative interventions, but these lack specific parameters to determine the optimal timing of surgery. METHODS: Using the GRADE system, published evidence was analyzed to generate weighted statements for stage, site, acuity of presentation, and hospital setting to specify when surgery should be pursued, the time and duration of oncologically acceptable delays, and when to utilize nonsurgical modalities to bridge the waiting period. RESULTS: Colorectal cancer surgeries-prioritized as emergency, urgent with imminent emergency or oncologically urgent, or elective-were matched against the phases of the pandemic. Surgery in COVID-19-positive patients must be avoided. Emergent and imminent emergent cases should mostly proceed unless resources are exhausted. Standard practices allow for postponement of elective cases and deferral to nonsurgical modalities of stage II/III rectal and metastatic colorectal cancer. Oncologically urgent cases may be delayed for 6(-12) weeks without jeopardizing oncological outcomes. Outside established principles, administration of nonsurgical modalities is not justified and increases the vulnerability of patients. CONCLUSIONS: The COVID-19 pandemic has stressed already limited health care resources and forced rationing, triage, and prioritization of care in general, specifically of surgical interventions. Established guidelines allow for modifications of optimal timing and type of surgery for colorectal cancer during an unrelated pandemic.

The role of cyclin D1 and Ki-67 in the development and prognostication of thin melanoma.

AIMS: Despite their low individual metastatic potential, thin melanomas (≤1 mm Breslow thickness) contribute significantly to melanoma mortality overall. Therefore, identification of prognostic biomarkers is particularly important in this subgroup of melanoma. Prompted by preclinical results, we investigated cyclin D1 protein and Ki-67 expression in in-situ, metastatic and non-metastatic thin melanomas. METHODS AND RESULTS: Immunohistochemistry was performed on 112 melanoma specimens, comprising 22 in situ, 48 non-metastatic and 42 metastatic thin melanomas. Overall, epidermal and dermal cyclin D1 and Ki-67 expression were semiquantitatively evaluated by three independent investigators and compared between groups. Epidermal Ki-67 expression did not differ statistically in in-situ and invasive melanoma (P = 0.7). Epidermal cyclin D1 expression was significantly higher in thin invasive than in in-situ melanoma (P = 0.003). No difference was found in cyclin D1 expression between metastatic and non-metastatic invasive tumours. Metastatic and non-metastatic thin melanomas did not show significant differences in epidermal expression of Ki-67 and cyclin D1 (P = 0.148 and P = 0.611, respectively). In contrast, strong dermal expression of Ki-67 was more frequent in metastatic than non-metastatic samples (28.6 versus 8.3%, respectively, P = 0.001). The prognostic value of dermal Ki-67 expression was confirmed by multivariate analysis (P = 0.047). CONCLUSION: We found an increased expression of cyclin D1 in invasive thin melanomas compared to in-situ melanomas, which supports a potential role of this protein in early invasion in melanoma, as suggested by preclinical findings. Moreover, our results confirm that high dermal Ki-67 expression is associated with an increased risk of development of metastasis in thin melanoma and could possibly serve as a prognostic biomarker in clinical practice, especially if combined with additional methods.

Effects of oral iron and calcium supplement on the pharmacokinetics and pharmacodynamics of molidustat: an oral HIF-PH inhibitor for the treatment of renal anaemia.

PURPOSE: The present studies assessed the drug-drug interaction of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, with iron and calcium supplements, which are common medications in patients with anaemia due to chronic kidney disease (CKD). METHODS: Forty-two healthy men received molidustat alone (fasted or fed) or combined with oral iron(II) or calcium(II), given immediately before or between 4 h before and 1 h after molidustat in three randomized, open-label, crossover studies (12-15 participants per study). Molidustat AUC and Cmax were assessed as the main pharmacokinetic parameters, and endogenous erythropoietin (EPO) was measured to evaluate pharmacodynamics. RESULTS: Depending on prandial state, concomitant intake of iron(II) reduced molidustat AUC and Cmax by 50-75% and 46-84%, respectively, and EPO AUC(0-24) and Cmax by 31-44% and 36-48%, respectively. The influence of iron(II) declined with increasing the time interval to the intake of molidustat, with reductions in molidustat AUC and Cmax of 9% and 10%, respectively, when iron(II) intake occurred 4 h before molidustat. Accordingly, effects on endogenous EPO were less pronounced with increased time separation between oral iron(II) and molidustat intake. Calcium(II) reduced molidustat AUC and Cmax by 15% and 47%, respectively, without influence on EPO response. All treatments were well tolerated. CONCLUSIONS: In contrast to concomitant oral intake of calcium, the effect of oral iron supplements on molidustat pharmacokinetics and pharmacodynamics should be considered, and the two agents should be administered with an appropriate time separation.

Myelin oligodendrocyte glycoprotein revisited-sensitive detection of MOG-specific T-cells in multiple sclerosis.

Autoreactive CD4+ T-cells are believed to be a main driver of multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG) is considered an autoantigen, yet doubted in recent years. The reason is in part due to low frequency and titers of MOG autoantibodies and the challenge to detect MOG-specific T-cells. In this study we aimed to analyze T-cell reactivity and frequency utilizing a novel method for detection of antigen-specific T-cells with bead-bound MOG as stimulant. Peripheral blood mononuclear cells (PBMCs) from natalizumab treated persons with MS (n = 52) and healthy controls (HCs) (n = 24) were analyzed by IFNγ/IL-22/IL-17A FluoroSpot. A higher number of IFNγ (P = 0.001), IL-22 (P = 0.003), IL-17A (P < 0.0001) as well as double and triple cytokine producing MOG-specific T-cells were detected in persons with MS compared to HCs. Of the patients, 46.2-59.6% displayed MOG-reactivity. Depletion of CD4+ T-cells or monocytes or blocking HLA-DR completely eliminated the MOG specific response. Anti-MOG antibodies did not correlate with T-cell MOG-responses. In conclusion, we present a sensitive method to detect circulating autoreactive CD4+ T-cells producing IFNγ, IL-22 or IL-17A using MOG as a model antigen. Further, we demonstrate that MOG-specific T-cells are present in approximately half of persons with MS.