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A method for the preparation of samples from a biological material for the detection of upconversion nanoparticles (UNPs) contained in it is proposed on the basis of confocal microscopy techniques. The method was tested by monitoring the natural excretion of an injected colloidal solution of YVO4:Yb, Er nanoparticles with sizes from 10 to 700 nm (0.2 mL, containing 15 mg UNPs and with a dosage of 600 mg/kg) into the body of Helix lucorum. The experiments showed that the animal excreted the nanoparticles from the body in a natural way within 3 days, while the excretion rate decreased over time. The sensitivity threshold in the experiments was one nanoparticle per 1 µL. [ABSTRACT FROM AUTHOR]

Dr. Deborah Birx, the White House Coronavirus Task Force coordinator, told NBC News on “Meet the Press” that “[T]he U.S. needs a ‘breakthrough’ in coronavirus testing to help screen Americans and get a more accurate picture of the virus’ spread.” We have been involved with biopathogen detection since the 2001 anthrax attacks and were the first to detect anthrax in real-time. A variation on the laser spectroscopic techniques we developed for the rapid detection of anthrax can be applied to detect the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2 virus). In addition to detecting a single virus, this technique allows us to read its surface protein structure. In particular, we have been conducting research based on a variety of quantum optical approaches aimed at improving our ability to detect Corona Virus Disease-2019 (COVID-19) viral infection. Indeed, the detection of a small concentration of antibodies, after an infection has passed, is a challenging problem. Likewise, the early detection of disease, even before a detectible antibody population has been established, is very important. Our team is researching both aspects of this problem. The paper is written to stimulate the interest of both physical and biological scientists in this important problem. It is thus written as a combination of tutorial (review) and future work (preview). We join Prof. Federico Capasso and Editor Dennis Couwenberg in expressing our appreciation to all those working so heroically on all aspects of the COVID-19 problem. And we thank Drs. Capasso and Couwenberg for their invitation to write this paper.

Multi-color fluorescent nanodiamonds (FNDs) containing a variety of color centers are promising fluorescent markers for biomedical applications. Compared to colloidal quantum dots and organic dyes, FNDs have the advantage of lower toxicity, exceptional chemical stability, and better photostability. They can be surface functionalized by techniques similar to those used for other nanoparticles. They exhibit a variety of emission wavelengths from visible to near infrared, with narrow or broad bandwidths depending on their color centers. In addition, some color centers can detect changes in magnetic fields, electric fields, and temperature. In this article review, we will discuss the current trends in FND’s development, including comparison to the early development of quantum dots. We will also highlight some of the latest advances in fabrication, as well as demonstrations of their use in bioimaging and biosensing.

Using the hydrothermal method, we synthesized water soluble YVO4: Yb, Er nanoparticles with a size less than 10 nm. Nanoparticles exhibit intense luminescence in the green region due to Er3+ ions when excited by laser radiation at a wavelength of 980 nm as a result of the up-conversion process. Bright and stable luminescence also persists in an aqueous solution of nanoparticles. Based on experimental data, it can be argued that the objects obtained are promising in biological applications, as well as up-conversion phosphors.

Objectives: In the Netherlands, limited variability exists in performance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) among centers treating colorectal peritoneal metastases (PM), except for the intraperitoneal drug administration. This offers a unique opportunity to investigate any disparities in survival between the two most frequently used HIPEC regimens worldwide: mitomycin C (MMC) and oxaliplatin., Methods: This was a comparative, population-based cohort study of all Dutch patients diagnosed with synchronous colorectal PM who underwent CRS-HIPEC between 2014 and 2017. They were retrieved from the Netherlands Cancer Registry. Main outcome was overall survival (OS). The effect of the intraperitoneal drug on OS was investigated using multivariable Cox regression analysis., Results: In total, 297 patients treated between 2014 and 2017 were included. Among them, 177 (59.6%) received MMC and 120 (40.4%) received oxaliplatin. Only primary tumor location was different between the two groups: more left-sided colon in the Oxaliplatin group (47.5% vs. 33.3%, respectively, p=0.048). The 1-, 2- and 3-year OS were 84.6% vs. 85.8%, 61.6% vs. 63.9% and 44.7% vs. 53.5% in patients treated with MMC and oxaliplatin, respectively. Median OS was 30.7 months in the MMC group vs. 46.6 months in the oxaliplatin group (p=0.181). In multivariable analysis, no influence of intraperitoneal drug on survival was observed (adjusted HR 0.77 [0.53-1.13])., Conclusions: Long-term survival between patients treated with either MMC or oxaliplatin during CRS-HIPEC was not significantly different., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: De Hingh: An unrestricted research grand from RanD/QPS and Roche, paid to the institute., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Competing Interests: Competing interests: GMvD and WBN received an unrestricted research grant made available to the institution for the development of optical molecular imaging from SurgVision B.V. (Groningen, the Netherlands). GMvD and VN are members of the scientific advisory board of SurgVision B.V.

A meta-analysis of the association of iron overload with gestational diabetes mellitus (GDM) may inform the health debate. We performed a meta-analysis investigating the association of iron biomarkers and dietary iron exposure with GDM. We identified 33 eligible studies ( N = 44,110) published in 2001⁻2017. The standardized mean differences (SMD) in women who had GDM compared to pregnant women without were 0.25 µg/dL (95% CI: 0.001⁻0.50) for iron, 1.54 ng/mL (0.56⁻2.53) for ferritin, 1.05% (0.02 to 2.08) for transferrin saturation, and 0.81 g/dL (0.40⁻1.22) for hemoglobin. Adjusted odds ratio for GDM were 1.58 (95% CI: 1.20⁻2.08) for ferritin, 1.30 (1.01⁻1.67) for hemoglobin, and 1.48 (1.29⁻1.69) for dietary heme intake. We did not find any differences in TIBC or transferrin concentration in women with and without GDM. We also did not find any association of increased transferrin receptor or increased intake of total dietary iron, non-heme iron or supplemental iron, with increased odds ratios for GDM. Considerable heterogeneity was present among the studies (0⁻99%), but no evidence of publication bias. Accumulating evidence suggests that circulating and dietary iron biomarkers among pregnant women are associated with GDM, but the results should be interpreted with caution due to the high heterogeneity of analyses. Randomized trials investigating the benefits of iron reduction in women at high risk for GDM are warranted., Competing Interests: The authors declare no conflict of interest.

Over the last few decades, in the field of minimally invasive adrenal surgery, retroperitoneoscopic adrenalectomy (PRA) has shown favorable results when compared to laparoscopic transperitoneal adrenalectomy (LTA). However, for many endocrine surgeons it is unclear if, when, and how to transition from LTA to PRA. Although the length of the learning curve for both approaches is comparable, the LTA is a technically more challenging procedure whilst PRA demands an orientation in a new environment in a patient that is positioned upside down. Visiting a proctor is crucial for successfully adopting the PRA procedure, and continued mentorship in a surgeon's own hospital during the first procedures is preferable. There are several other aspects related to the decision to transition to PRA; the caseload of adrenal patients, learning aspects of other members of the team, technical considerations, case selection, and a well-developed emergency plan in case of complications during surgery. In a dedicated endocrine center with a considerable annual case load of approximately 30 procedures, we recommend to transition to PRA in order to provide the highest quality of care to adrenal patients.

Background: In the Netherlands, surgery for peritoneal metastases of colorectal cancer (PMCRC) is centralised, whereas PMCRC is diagnosed in all hospitals. This study assessed whether hospital of diagnosis affects treatment selection and overall survival (OS)., Methods: Between 2005 and 2015, all patients with synchronous PMCRC without systemic metastases were selected from the Netherlands Cancer Registry. Treatment was classified as cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), systemic therapy or other/no treatment. Hospitals of diagnosis were classified as: (1) non-teaching or academic/teaching hospital and (2) HIPEC centre or referring hospital. Referring hospitals were further classified based on the frequency of CRS/HIPEC as high-, medium- or low-frequency hospital. Multivariable regression analyses were used to assess the independent influence of hospital categories on the likelihood of CRS/HIPEC and OS., Results: A total of 2661 patients, diagnosed in 89 hospitals, were included. At individual hospital level, CRS/HIPEC and systemic therapy ranged from 0% to 50% and 6% to 67%, respectively. Hospital of diagnosis influenced the likelihood of CRS/HIPEC: 33% versus 13% for HIPEC centres versus referring hospitals (odds ratio (OR) 3.66 [2.40-5.58]) and 11% versus 17% for non-teaching hospitals versus academic/teaching hospitals (OR 0.60 [0.47-0.77]). Hospital of diagnosis affected median OS: 14.1 versus 9.6 months for HIPEC centres versus referring hospitals (hazard ratio (HR) 0.82 [0.67-0.99]) and 8.7 versus 11.5 months for non-teaching hospitals versus academic/teaching hospitals (HR 1.15 [1.06-1.26]). Compared with diagnosis in medium-frequency referring hospitals, median OS was increased in high-frequency referring hospitals (12.6 months, HR 0.82 [0.73-0.91]) and reduced in low-frequency referring hospitals (8.1 months, HR 1.12 [1.01-1.24])., Conclusion: Treatment disparities among hospitals of diagnosis and their impact on survival indicate suboptimal treatment selection for PMCRC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Optimum cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is essential for the curative treatment of peritoneal carcinomatosis of colorectal origin. At present, surgeons depend on visual inspection and palpation for tumour detection. Improved detection of tumour tissue using molecular fluorescence-guided surgery could not only help attain a complete cytoreduction of metastatic lesions, but might also prevent overtreatment by avoiding resection of benign lesions., Methods: For this non-randomised, single-centre feasibility study, we enrolled patients with colorectal peritoneal metastases scheduled for cytoreductive surgery and HIPEC. 2 days before surgery, 4·5 mg of the near-infrared fluorescent tracer bevacizumab-IRDye800CW was administered intravenously. The primary objectives were to determine the safety and feasibility of molecular fluorescence-guided surgery using bevacizumab-IRDye800CW. Molecular fluorescence-guided surgery was deemed safe if no allergic or anaphylactic reactions were recorded and no serious adverse events were attributed to bevacizumab-IRDye800CW. The technique was deemed feasible if bevacizumab-IRDye800CW enabled detection of fluorescence signals intraoperatively. Secondary objectives were correlation of fluorescence with histopathology by back-table imaging of the fresh surgical specimen and semi-quantitative ex-vivo analyses of formalin-fixed paraffin embedded (FFPE) tissue on all peritoneal lesions. Additionally, VEGF-α staining and fluorescence microscopy was done. This study is registered with the Netherlands Trial Registry, number NTR4632., Findings: Between July 3, 2014, and March 2, 2015, seven patients were enrolled in the study. One patient developed an abdominal sepsis 5 days postoperatively and another died from an asystole 4 days postoperatively, most probably due to a cardiovascular thromboembolic event. However, both serious adverse events were attributed to the surgical cytoreductive surgery and HIPEC procedure. No serious adverse events related to bevacizumab-IRDye800CW occurred in any of the patients. Intraoperatively, fluorescence was seen in all patients. In two patients, additional tumour tissue was detected by molecular fluorescence-guided surgery that was initially missed by the surgeons. During back-table imaging of fresh surgical specimens, a total of 80 areas were imaged, marked, and analysed. All of the 29 non-fluorescent areas were found to contain only benign tissue, whereas tumour tissue was detected in 27 of 51 fluorescent areas (53%). Ex-vivo semi-quantification of 79 FFPE peritoneal lesions showed a tumour-to-normal ratio of 6·92 (SD 2·47)., Interpretation: Molecular fluorescence-guided surgery using the near-infrared fluorescent tracer bevacizumab-IRDye800CW is safe and feasible. This technique might be of added value for the treatment of patients with colorectal peritoneal metastases through improved patient selection and optimisation of cytoreductive surgery. A subsequent multicentre phase 2 trial is needed to make a definitive assessment of the diagnostic accuracy and the effect on clinical decision making of molecular fluorescence-guided surgery., Funding: FP-7 Framework Programme BetaCure and SurgVision BV., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The extralevator abdominoperineal excision (ELAPE) procedure creates an extensive soft tissue defect of the pelvic floor. It has been suggested that primary reconstruction reduces the risk of wound infection and delayed wound healing in this high-risk area. Use of myocutaneous flaps or omentoplasty are associated with functional limitations and complications. We performed the perineal variant of the lotus petal flap, which was originally described for vulvar reconstruction. We aimed to verify if application of the lotus petal flap in pelvic floor reconstruction after ELAPE meets the goals of an ideal reconstruction., Methods: We performed a retrospective study of 28 patients who underwent the lotus petal flap procedure for pelvic floor reconstruction after ELAPE between January 2011 and March 2014., Results: Median age was 62.1 years and 78.6 % of patients were female. In most patients the tumor was preoperatively irradiated (89.3 %) and in 28.6 % of the reconstructions a biological mesh was applied. No total flap loss occurred. Six (21.4 %) patients had no complications, while 13 (46.4 %) patients had minor complications (Clavien-Dindo grade I-II). Reoperation (Clavien-Dindo grade IIIb) was performed in nine patients (32.1 %), three of whom required a second lotus petal flap reconstruction. Median time until wound healing was 14 weeks. No additional surgery was performed for aesthetic problems., Conclusions: Reconstruction of the pelvic floor after ELAPE using the fasciocutaneous lotus petal flap has limited major complications, but still with a high incidence of minor wound complications. This retrospective cohort study shows limited consequences on form and function.

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay., Methods/design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 °C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA., Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival., Trial Registration Number: NCT02231086 (Clinicaltrials.gov).

Purpose: This article summarises the results of a newly developed technique that utilises Meniscus Arrows(®) for the arthroscopic fixation of displaced tibial spine fractures in children and adolescents., Method: Twelve tibial spine fractures in the knees of eleven children between 6 and 15 years old, with an average age of 12 years, were arthroscopically fixed with Meniscus Arrows(®), after a reduction of their fractures. This was followed by 5 weeks immobilisation in a plaster of Paris. Postoperative follow-up included radiographs, Lachmann tests on all of the children's knees and KT-1000 tests of eight out of twelve of the children's knees. The postoperative follow-up time ranged from 3 to 10 years, with patients being seen for an average of 4 years., Results: All of the fractures consolidated uneventfully, and all of the patients returned unrestricted to their previous activity level. The Lachmann tests revealed no, or a non-functional, laxity in any of the patients' knees. The KT-1000 tests showed a difference between the operated side, and non-operated side, of between 3 mm in the first knee operated on and an average of 1 mm in the remaining knees., Conclusion: The arthroscopic fixation of tibial spine fractures using Meniscus Arrows(®) showed that this minimally invasive procedure resulted in the uneventful consolidation of all twelve of the fractures, with excellent results, and without the need for a second, hardware removal, operation., Level of Evidence: Level IV.

Objective: Despite improvements in anesthesiology and intensive care medicine, mortality for perforated gastroduodenal ulcer disease remains high. This study was designed to evaluate the results of surgery for perforated ulcer disease and to identify prognostic factors for mortality in order to optimize treatment., Patients and Methods: The medical records of 272 patients undergoing emergency surgery for perforated ulcer disease from 2000 to 2005 in two large teaching hospitals and one university hospital in the Netherlands were retrospectively analyzed. Information on 89 pre-, peri- and postoperative data were recorded. Statistical analysis was performed using multiple logistic regression analysis. The primary endpoint was 30-day mortality., Results: The 30-day mortality rate was 16%. Variables associated with 30-day mortality were age, shock, tachycardia, anemia and ASA class., Conclusions: A relatively low 30-day mortality rate was achieved. Age, shock, tachycardia and anemia were significantly associated with 30-day mortality. Finding that shock, tachycardia and anemia are independently associated with 30-day mortality could indicate that patients are septic upon admission. Improvements in survival might be achieved by early sepsis treatment., (Copyright © 2011 S. Karger AG, Basel.)

Aim: To analyse the results of needle localised biopsy (NLB) for non-palpable breast lesions in our hospital and to compare them with data on stereotactic large-core biopsy (SCB), which has been recently introduced as a new less invasive method for evaluating mammographic abnormalities., Methods: We evaluated the results of all consecutive NLB procedures in our hospital in the period 1998-2000 and compared them with data from literature. Clinical, mammographic and pathological data were reviewed., Results: In the present study 314 patients with 319 non-palpable mammographic abnormalities were included. Seventy percent of patients were referred to us from the national screening program. In all but one patient the NLB procedure was successful. The mean duration of hospital stay was 3 (1-10) days. Histological diagnosis was invasive carcinoma in 31%, invasive carcinoma with DCIS in 32%, DCIS alone in 13% and benign in 24%. The invasive carcinoma group scored tumour-free margins after the first operation in 77% of patients, for both the DCIS with invasive carcinoma group and DCIS alone group the tumour-free margin rate was 47%. Patients with invasive carcinoma and/or DCIS were re-operated in 88%. Of all procedures, 91% was performed without complications., Conclusion: NLB is a safe, relatively simple procedure with a high diagnostic accuracy combined with a lower failure and false-negative rate compared to SCB.