Our data support the use of fiducial markers for safer and more accurate liver SBRT.Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm,  Stereotactic body radiotherapy (SBRT) delivers conformal high-dose radiation and is used as focal liver therapy in the management of primary liver cancers and oligometastatic lesions with excellent local control rates of >80% ,2,3,4. GThe utilization of fiducial markers for IGRT alignment during SBRT has been shown to be an effective radio-opaque surrogate for tumor position . TreatmeLimited data exist comparing liver edge versus fiducial markers as a surrogate for tumor localization, when evaluating the accuracy of liver SBRT delivery. In this study, we aim to define the benefit of fiducial-based alignment and analyze inter-observer reliability in target alignment for liver SBRT.Between November 2015 and May 2018, nineteen patients with 24 liver tumors were treated with SBRT on a TrueBeamSTX linear accelerator  at a single institution. Prior to treatment, 1–4 gold fiducial markers  were implanted by an interventional radiologist in close proximity to the tumor under computed tomography (CT) guidance approximately 1 week prior to treatment. A planning CT scan with intravenous contrast was performed followed by a four-dimensional (4D) CT scan to assess organ motion. To minimize motion, all patients were planned for using either abdominal compression or amplitude-based respiratory gating at the discretion of the treating physician. The gross tumor volume (GTV) was defined using the planning CT or a magnetic resonance imaging (MRI) scan. When feasible, an internal target volume (ITV) was drawn to include the respiratory-related motion of the tumor and a uniform expansion of 5 mm was utilized to create the planning target volume (PTV). Treatment planning was completed in Eclipse using volumetric modulated arc therapy . Prior to treatment, a CBCT scan was acquired and aligned to the planning CT using the fiducials as a guide. All data were collected under an institutional review board-approved protocol for retrospective data analysis.To quantify the accuracy of fiducial marker-based localization, seven observers (Radiation Oncology physicians) retrospectively analyzed the CBCT scans acquired before each fraction. The Aria Eclipse platform was used for target localization through viewing CBCT scans in the offline review mode. For each CBCT, two alignments were performed . First, t-test.The error in each observation was calculated as the shift relative to the ground truth alignment. The uncertainty for both fiducial and liver edge alignment was calculated using inter-observer variability  of the observed positions). Descriptive statistics were used to evaluate the impact of the target size, distance to the closest liver surface, and distance to the liver dome caused by the shift magnitude. Patients were divided into two groups based on the median of each clinical factor, and the means of these groups were compared using a 3 (range 0.2–291 cm3) and median PTV was 38.5 cm3 (range 3.8–453 cm3). All patients had at least one radio-opaque marker located near the liver lesion, with a median of 2 fiducials (range 2–4) being placed. In two cases, surgical clips or lipiodol were used for localization.The tumor characteristics for 19 patients are summarized in The mean absolute error and uncertainty determined by seven observers using the liver surface or fiducial markers for patient realignment are shown in In order to identify patients that may especially benefit from fiducial placement, several patient-specific parameters were analyzed for correlation with the surface-based set-up error. These parameters included the GTV volume, distance to closest liver surface, and distance from the superior tumor margin to the liver dome. These results are shown in This is the first study specifically designed to determine the utility of fiducial-based alignment compared to liver edge-based alignment, and the inter-observer reliability of these alignments were investigated. We discovered that treatment set-up without fiducial markers in liver SBRT leads to a significantly greater mean positional error of 5.3 mm compared to that of 1.5 mm with a fiducial-based set-up. Inter-observer variability between seven observers was significantly higher when aligning to the liver edge versus to fiducial markers, specifically, 4.5 mm versus 1.8 mm, respectively, suggesting that fiducial markers allow more accurate and reproducible liver SBRT delivery.p < 0.001) with increased distance between the marker and tumor. The random and systematic prediction error SDs at a marker tumor distance of 2 cm were 1.0 mm and 1.2 mm, respectively [Implanted fiducial markers have demonstrated trends of improved local control  and supeectively . Finallyectively . The larp = 0.003). These patients may potentially derive additional benefit from fiducial marker placement as the liver dome may serve as a reproducible landmark for daily set--up whereas other regions of the liver may be more difficult to align on CBTC scans due to the presence of more deformation and the lack of identifiable landmarks.In this study, we utilized the closest fiducial from the tumor with an average distance of 0.4 cm and found significantly decreased random and systematic errors of 1.5 mm and 1.8 mm when compared to those of a liver surface surrogate whereby the random and systematic errors were 5.3 mm and 4.5 mm, respectively, similarly to those of some of the conventional surrogates used. We identified that tumors 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials -based linear accelerators that can better localize (a) liver tumor(s).


Social vulnerability impacts the transmission of SARS-CoV-2 (SCV2) among household contacts. Understanding these correlates can inform interventions to prevent infection among close contacts. We examined whether the social vulnerability index (SVI), a composite measure of socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation, is associated with the risk of SCV2 infection among household contacts.Overall Social Vulnerability Index DiagramWe used data from a multi-site, prospective, case-ascertained household transmission study with daily nasal swabs for 10 days and RT-PCR testing to detect SCV2 infections in household contacts. Age and gender were self-reported and vaccination status was self-reported and verified. We mapped households to 2020 census tracts and the 2020 SVI . We examined the association between census tract-level SVI (in quartiles) and the risk of infection among household contacts using Poisson regression with generalized estimating equations, accounting for household clustering.Inclusion criteria for analysis in this study.Inclusion criteria for analysis in this study.Among 1,171 household contacts from 719 households, 67.4% developed SCV2 infection. After adjusting for the age of the contact and study site, contacts living in the most vulnerable SVI quartiles, Q3  and Q4 , had higher rates of infection compared to those living in the least vulnerable quartile (Q1) at the census tract level. To describe the effect of SVI accounting for vaccination, we performed a second regression adjusting for vaccine receipt among participants. We found that Q3  still had higher rates of infection compared to those living in the least vulnerable quartile (Q1). Q4 was directionally consistent but confidence bounds crossed 1 .Household contacts from census tracts with greater social vulnerability at the census tract level had a greater risk of SCV2 infection. These risks held even after accounting for vaccine receipt among participants. Future public health interventions should focus on reducing infection and transmission among individuals living in areas with higher social vulnerability beyond vaccination coverage.Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support Suchitra Rao, MBBS, MSCS, Sequiris: Advisor/Consultant Edwin J. Asturias, MD, Hillevax: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Grant/Research Support Huong McLean, PhD, MPH, Seqirus: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member


Neuroendocrine tumours, recently reclassified as neuroendocrine neoplasms (NENs), are a heterogeneous group of tumours with variability in their disease course and outcome. Complex mechanisms involving spatial and temporal changes in tumour biology affect their treatment response and survival. Treatment strategies are often based on information regarding tumour stage and grade. Tumour heterogeneity, however, is a common phenomenon in NENs, and it is not uncommon for these neoplasms to show intra- and inter-tumour heterogeneity that may lead to incomplete understanding of their tumour biology and behaviour. This review summarises the available evidence on gastroenteropancreatic NEN heterogeneity and its impact on diagnosis and clinical management.Tumour heterogeneity is a common phenomenon in neuroendocrine neoplasms (NENs) and a significant cause of treatment failure and disease progression. Genetic and epigenetic instability, along with proliferation of cancer stem cells and alterations in the tumour microenvironment, manifest as intra-tumoural variability in tumour biology in primary tumours and metastases. This may change over time, especially under selective pressure during treatment. The gastroenteropancreatic (GEP) tract is the most common site for NENs, and their diagnosis and treatment depends on the specific characteristics of the disease, in particular proliferation activity, expression of somatostatin receptors and grading. Somatostatin receptor expression has a major role in the diagnosis and treatment of GEP-NENs, while Ki-67 is also a valuable prognostic marker. Intra- and inter-tumour heterogeneity in GEP-NENS, however, may lead to inaccurate assessment of the disease and affect the reliability of the available diagnostic, prognostic and predictive tests. In this review, we summarise the current available evidence of the impact of tumour heterogeneity on tumour diagnosis and treatment of GEP-NENs. Understanding and accurately measuring tumour heterogeneity could better inform clinical decision making in NENs. Tumour heterogeneity refers to spatial and temporal variations that may occur within the tumour environment (intra-tumour) or within individual tumour foci, and also between tumour sites (inter-tumour) . Such heNeuroendocrine tumours (NETs), better defined as neoplasms (NENs), are a heterogeneous group of neoplasms that range from well-differentiated tumours to more aggressive carcinomas  11]..11].The hallmark of NENs is their expression of somatostatin receptors (SSTRs), as somatostatin inhibits cell growth and hormone secretion in normal and cancerous neuroendocrine cells . SomatosThe GEP tract is the most common site for NENs, with the small intestine (SI) and the pancreas being the most prevalent sites of origin for more advanced neoplasms. For these neoplasms, treatment strategies are based on information on SSTRs expression, tumour stage and grade (including differentiation) and the expression of neuroendocrine biomarkers .The definitive diagnosis of an NEN is made by histopathological examination of tumour tissue, obtained either via a biopsy or following surgery. Morphologic imaging, however, is essential as a baseline evaluation for staging, in particular for identifying the presence of metastases, while functional imaging is important to assess the functional and metabolic status of the tumour. Combining morphological  and functional imaging techniques is fundamental in the decision-making process of the therapeutic approach to patients with GEP-NENs . GalliumSpatial and temporal heterogeneity should be taken into account in the assessment of NENs, as it is not uncommon for GEP primary and metastatic sites to show intra-tumour and inter-tumour heterogeneity in their Ki-67 index, as well as in their SSTR expression and cell signalling pathways, leading to incomplete understanding of their tumour biology and behaviour ,29,30,31The aim of this review is to summarise the current available evidence on tumour heterogeneity in GEP-NENs (pancreatic and SI), and to evaluate the impact of this on clinical practice. We initially summarise the current available evidence on tumour heterogeneity in GEP-NENs. We then describe the manifestations of tumour heterogeneity and highlight their influence on diagnosis and clinical practice. Finally, we analyse the major problems limiting the efficacy of targeted strategies and affecting treatment outcomes.Spatial and temporal heterogeneous expression of SSTRs, Ki-67 and cell signalling pathways can be used to predict tumour progression, prognosis and response to targeted therapeutic strategies ,26,32. UTumour heterogeneity is a common phenomenon in GEP-NENs  and has Pancreatic NENs can show a progressive increase in their Ki-67 index or progression to a more aggressive disease, events that are linked to poorer prognosis ,35. ChanSmall-intestine NENs are generally considered to have a relatively low somatic mutation rate, but a more florid epigenetic derangement. It has been shown, however, that there is a high degree of genetic variability between the primary site and liver metastases . AlthougSomatostatin receptor imaging is essential for the detection and characterisation of GEP-NENs, and adequate uptake is an important requirement for the use of SSAs and PRRT. The expression of SSTR2 is an independent positive prognostic factor for survival being linked to a longer overall survival following PRRT. Conversely, SSTR5 expression in GEP-NENs seems to be related to angioinvasion and metastases ,49,50,51In less differentiated NENs that often co-express SSTRs and glucose-transporters, the addition of flourine-18 fluorodeoxyglucose (18F-FDG)-PET imaging can potentially better assess the intra- and inter-lesional heterogeneity of the tumour by exploring the heterogeneous distribution and uptake of 18F-FDG  52]..52].18F-FDG-PET might be a useful addition to SSTR-based imaging in NENs with higher mitotic rates but well-differentiated morphology, i.e., for grade 3 GEP-NETs . They miIn NENs, random biopsies may not be representative of the whole tumour burden, especially for higher-grade tumours and metastatic disease, which often display a different clinic-pathological pattern from their primary site. More than half of metastatic GEPs and SI-NENs show a higher Ki-67 index on definitive histology and a subsequent change in World Health Organization grade ,29,30,31Tissue sample requirement  and sampling modality are important factors in ensuring reliable results. Most of the evidence available is on pancreatic NENs, as primary SI-NENs are often inaccessible to biopsy, forceps biopsy is technically challenging for lesions located deep in the mucosa or sub-mucosa, and there is no validated cytology reporting system ,88,89. SFor neuroendocrine liver metastases, FNA has been used to confirm diagnosis and to assess tumour grading ,104. In As NENs are often multifocal, and as there is often inter-tumour heterogeneity between primary and metastatic disease, the need for multi-regional and multi-site biopsies needs to be raised, as a single tumour-biopsy may be inadequate to assess the mutational landscape of NENs ,110,111.In light of the complexity of NENs, a multidisciplinary approach and the integration of clinical, biological, imaging and pathological information are essential and fundamental to guide a tailored approach. Receptor-based imaging has been shown to correlate with the disease phenotype and the expression of SSTRs, as in most cases the high expression of SSRT is linked to a well-differentiated tumour. Positive 18F-FDG-PET uptake seems to correlate well with the Ki-67 index and the presence of tumour heterogeneity. In particular, 18F-FDG-PET might be helpful in the selection of target lesions to biopsy in other types of NENs ,122,123.Peptide receptor radionuclide therapy is mainly used as second-line therapy for metastatic, inoperable, or progressive well to moderately differentiated NENs that originate from the GEP tract ,126,127.Responses to PRRT are unpredictable . Among tThe use of 18F-FDG PET in the assessment of tumour progression, survival and the response to PRRT has shown a predictive value in patients with advanced NENs, thus 18F-FDG uptake could be more useful for high-grade NENs that often lose SSTR expression ,132. AltPatients with insufficient tumour uptake on SSTR imaging seem to have worse outcomes and a much lower survival even when receiving more aggressive treatment. This could be linked to an epigenetic gene silencing associated with abnormal tumour growth . Of noteTemporal heterogeneity can be a cause of progression or relapse after PRRT as the majority of patients with initially stable disease, despite initial high disease control rates, will eventually progress ,150,151.Somatostatin analogue therapy for NENs has been used to control symptoms in patients with functioning GEP-NENs since the late 1980s, and its use has subsequently been extended to treat all symptomatic NENs . CurrentWell-differentiated SI and pancreatic NENs generally express high levels of SSTR2, especially in tumours with a low Ki-67 index (≤2%) ,50,157. Intra-tumour and inter-tumour (between primary and metastatic disease) heterogeneity in the expression of SSTR2 in NENs has also been demonstrated ,48. InteMost primary NENs express SSTR2, in particular, isoform A. Locoregional and distant metastases often maintain the same level of SSTR2 expression. However, it seems that other SSTRs, such as SSTR5, may be overexpressed in metastatic disease. Immunohistochemistry staining performed on well-differentiated GEP-NENs showed that the expression of SSTR5 was higher in distant metastases in comparison to their primary site. Moreover, tumours showed intra-tumour heterogeneity for both receptors . It seemIn NENs, several pathways play a major role in cancer growth and metastasis, and have recently been explored as possible treatment targets in advanced cases . It is nThe PI3K/protein kinase B (AKT)/mTOR_signalling pathway plays a fundamental role in the regulation of cell growth and proliferation, angiogenesis, nutrient availability, metabolism, and apoptosis . The mTOUnfortunately, resistance to mTOR inhibitors is a common phenomenon and disease stabilization is mainly responsible for the improvement in progressive-free survival There are several possible mechanisms for rapamycin resistance and treatment failure, with tumour heterogeneity being one of the possible contributing factors. Spatial heterogeneous alterations in the mTOR pathway could affect response to treatment, as the coexistence of different mutations could lead to rapamycin resistance .There are only few studies available that have investigated tumour heterogeneity in the mTOR pathway in GEP-NENs .In a study of 27 cases of synchronous well-differentiated grade 1 metastatic SI-NETs, it was shown that although mTOR activation was present in most of the cases, in the primary and the metastatic sites , a difference in the activation and regulation of this pathway was noted between the primary and metastatic sites. In particular, more than 95% of the liver metastases showed a higher activation of this signalling pathway with overexpression of different components of the pathway . A molecOne of the major issues of targeted therapy is the development of treatment resistance, as cancer cells are able to adapt and resist under selective treatment pressure. The presence within the tumour of subpopulations of cancer cells that are able to escape immune surveillance and evolve over time accounts for the development of treatment resistance and disease progression .Despite the effectiveness of different treatment options for NENs, relapse and progression are common, and up-to-date strategies to address NEN heterogeneity are needed. The approaches to tackle spatial and temporal heterogeneity can be directed toward either identifying predictive and prognostic biomarkers for treatment success and/or designing optimal treatment sequencing and combination to minimize relapse and progression.In the era of personalized medicine, attention is now focused on finding alternative methods to biopsy that are reliable, minimally invasive, easy to perform and repeatable over the course of the disease. Several strategies have been developed. For NENs, there is preliminary evidence for the usefulness of several techniques, but further studies are needed to confirm whether these techniques have a role to play.Liquid biopsies have been proposed as a less invasive alternative to tissue biopsy that also allows identification of minimal residual disease and the detection of resistance mechanisms. Moreover, liquid biopsies could be a valuable tool in detecting inter-tumour heterogeneity in circulation cancer cell clones . For NENSingle-cell RNA sequencing has been used in different cancers to identify intra-tumoural cell heterogeneity that could explain relapse and recurrence after treatment . Its potAdvanced image analysis (radiomics) has enabled the extraction of accurate quantitative information on spatial and longitudinal heterogeneity of tumour biology from routinely acquired tumour imaging . This meThe evaluation of tumour heterogeneity could also be particularly useful in guiding treatment selection at diagnosis and following recurrence, as outcomes could be improved by targeting different components of the disease. The choice of subsequent treatment should be based on tumour biology at the time of recurrence or progression ,201. ForThe evidence on NENs heterogeneity has grown significantly in the last decade, though much still needs to be investigated. The link between spatial and temporal tumour heterogeneity in the expression of targets and patient outcomes has been highlighted, showing how this information needs to be considered for a more individualized treatment strategy. A single standard fixed diagnostic algorithm may not work for this highly heterogeneous group of tumours. Individualized strategies in NEN diagnosis can lead to improved outcomes, better selection of candidates for specific treatment and evaluation in the post-treatment setting. Single tumour biopsies seem to be inadequate for characterizing the whole landscape of alterations of NENs, as they may failure to capture the real behaviour of the disease. Metastatic lesions are often discordant from the primary tumour as they often show features that were not present in the primary tumour. Temporal heterogeneity is also a consequence of treatment selective pressure and repeat biopsies should be considered at the time of initial recurrence or disease progression. On a practical level, however, extensive and repeat investigations may not be feasible with regards to safety and costs. The increase in the amount of information available from tumour biology will eventually create many challenges in the clinical setting. Future research should therefore also focus on identifying new modalities and relevant markers that can simplify the treatment decision-making process and optimize treatment.


In this case report, we describe two unusual presentations of varicella-zoster virus (VZV) reactivation without rash, a condition known as Zoster Sine Herpete (ZSH). In Case 1, a 58-year-old woman presented with severe right-sided chest pain under her breast that radiated to the ipsilateral back. After the initial workup ruled out cardiac and musculoskeletal etiologies, the characteristic dermatomal distribution of pain made us suspect VZV reactivation. A diagnosis of ZSH was made with positive VZV IgG and IgM serologies and symptomatic relief after famciclovir treatment. In Case 2, a 43-year-old woman presented with a severe headache and resolved sharp right flank pain. She was diagnosed with varicella meningitis after cerebrospinal fluid showed positive VZV DNA. Intravenous acyclovir treatment resulted in symptom resolution. The most common presentation of VZV reactivation is Herpes Zoster, or shingles, making ZSH a frequently missed diagnosis. High clinical suspicion is warranted to prevent life-threatening complications of ZSH. Zoster Sine Herpete (ZSH) is a consequence of varicella-zoster virus (VZV) reactivation, presenting with dermatomal neuralgia in the absence of rash . More frSince HZ is a common disease, ZSH, which shares the same pathophysiology, warrants attention in the differential diagnosis for dermatomal neuralgia. A thorough work up is needed to rule out other diagnosis causing similar symptoms and could also present with a rash like herpes simplex virus, impetigo, candidiasis, autoimmune disease, contact dermatitis, dermatitis herpetiformis, insect bites, and drug eruptions . ZSH is In rare cases, VZV reactivation manifests as meningitis or encephalitis, in which headache, nuchal rigidity, and/or altered mental status are the predominant symptoms. Such a diagnosis is challenging in the absence of a characteristic rash, as in the case of ZSH. Identifying ZSH as the cause of neurological symptoms becomes urgent in these cases given its communicable nature and the increased risk of morbidity related to CNS infections.Currently, ZSH can be tested via polymerase chain reaction (PCR) for VZV DNA, analysis of cerebrospinal fluid (CSF) or peripheral blood mononuclear cells for VZV DNA, and anti-VZV IgM and/or IgG antibodies . In the A 58-year-old female presented to the emergency department with central and right-sided chest pain under her breast. It started a month ago as a dull ache but rapidly increased in severity over the last two days. The pain was described as 9/10 in intensity, and was sharp, burning, and radiating to her back. There was associated shortness of breath. She denied fevers, weight loss, muscle weakness, or loss of sensation. A few days ago, the patient visited her primary care physician who prescribed cyclobenzaprine and recommended physical therapy which provided minimal relief. Her past medical history was significant for type II diabetes mellitus, hypertension, morbid obesity, and hyperlipidemia. Family history and social history were unremarkable with no history of drug, alcohol, or tobacco use.On arrival, her vital signs were within normal limits. She appeared in acute distress, but exams of cardiac, pulmonary, and other systems were unremarkable. Dermatologic examination revealed no rash or erythema in the affected region Fig. a, b. IntVarious causes of chest pain were considered and ruled out. Serial electrocardiograms (EKGs) and cardiac enzymes × 2 followed by a complete cardiac work-up were unremarkable. Chest computed tomography (CT) showed no acute pulmonary pathology. A thoracic spine magnetic resonance imaging (MRI) was only remarkable for mild degenerative changes, ruling out radicular pain. Urine analysis, urine culture, and blood cultures ruled out acute pyelonephritis and the possibility of sepsis.Once cardiac, pulmonary, and musculoskeletal etiologies were ruled out, the possibility of shingles was considered. However, the absence of any cutaneous manifestations was baffling. Viral serologies for VZV immunoglobulins were sent and the patient was started on oral famciclovir , and oral pregabalin . Over the next 48 h, the patient reported significant improvement in her pain. Serologies came back positive for both IgM and IgG. Additionally, patient confirmed a history of childhood varicella infection. A diagnosis of Zoster Sine Herpete was thus made based on positive serologies, T4-T5 dermatomal neuralgia, atypical absence of rash, and robust clinical response to famciclovir and pregabalin.A 43-year-old female with a past medical history of anxiety, childhood chickenpox, and 18 months post-partum presented to the emergency department with a 2-day history of severe headache and progressive photophobia. Six days prior to presentation, she had an acute-onset sharp pain in the right mid-abdomen radiating to the right flank and mid-back, which had self-resolved. The headache was localized frontally, non-pulsatile, and was associated with nausea, vomiting, and photophobia. She took naproxen without improvement. She denied recent trauma, viral illness, or contact with shingles or chickenpox. VZV IgM was obtained with her primary care physician 2 days ago and was negative.Vital signs and labs were all within normal limits. Physical exam revealed an uncomfortable-appearing woman but was otherwise unremarkable. Initial skin examination was unrevealing. Basic infectious workups including COVID-19, influenza A/B, and RSV were negative. CT Fig.  and CT A2O), and undetectable VZV DNA by PCR, confirming robust acyclovir treatment response. We stopped intravenous acyclovir on day 10 of treatment due to the patient’s need to breastfeed, and she was discharged home without complications.Because her symptoms and CSF results suggested meningitis, empiric intravenous acyclovir  and ceftriaxone 2 g, BID) were started. On hospital day 2, revisiting her presenting symptoms revealed a possibility of VZV reactivation. VZV PCR on CSF and repeat VZV serologies were obtained. Results demonstrated negative VZV IgM but positive IgG Table a. Over t g, BID wZoster Sine Herpete is a condition manifesting as dermatomal neuralgia in the absence of a rash . It has Currently, no studies have investigated the epidemiology of ZSH. However, since the annual rate of HZ ranges from 0.3 to 0.4% in the United States , and morP = 0.0007) at one month after symptom onset [In the two cases, VZV immunoglobulins had varied utility in diagnosis and treatment. Patient 1’s positive VZV IgM, IgG, and overall clinical presentation led to the diagnosis of ZSH, whereas patient 2’s negative IgM resulted in a short delay of diagnostic suspicion. The detection of VZV-specific immunoglobulins via enzyme-linked immunosorbent assay has both low sensitivity and low specificity , and a pom onset , validatP = 0.0012), leading to more opioid usage by patients with ZSH vs HZ  [Post-herpetic neuralgia is a common complication of shingles and can be a sequela of ZSH as well. Our patient in Case 1 suffered from dermatomal neuralgia for more than a month, whereas our second patient only had transient neuralgia, resolved before presentation to the hospital. Interestingly, a recent study found that the severity of pain and the prevalence of post-herpetic neuralgia were increased in ZSH compared to Herpes Zoster  . Post-heR, 9.00) , 15. SinThe prevalence of VZV-associated meningitis has been reported to be 8% in a study of 144 patients with aseptic meningitis . A form Zoster Sine Herpete (ZSH) is a rare presentation of VZV reactivation. It can be seen in both immunocompromised and immunocompetent individuals, and can be associated with post-herpetic neuralgia, especially in immunocompromised hosts. ZSH is likely underreported and underdiagnosed due to the atypical absence of a rash and non-routine testing. The clinicians should play a role in educating patients and have a low threshold of conducting thorough workup, especially in immunocompromised patients presenting with herpes zoster-like symptoms without rash, to diagnose and treat such conditions in a timely manner. Early diagnosis with VZV PCR and treatment with appropriate antivirals can significantly improve patients’ pain and prevent life-threatening neurological sequelae such as meningitis. These two cases highlight the importance of including ZSH as a differential diagnosis in relevant clinical scenarios and call for astute clinical judgement and a high index of suspicion to prevent potential significant complications of ZSH.


Biomaterials Research (2023) 27:6410.1186/s40824-023-00402-wThe original article [1] contains an incorrect grant number in the Funding section. The grant number ‘21871180’ should instead be ‘81872121’.


Sand dams are a form of rainwater harvesting, prolific in arid and semi-arid lands. Water is provided partly via handpumps, which, as the only improved method of abstraction from sand dams, are important for drinking water security. Accelerometers and cellular transmitters were fitted to 30 handpumps by the Africa Sand Dam Foundation (ASDF) in 2019 to monitor the use and reliability of the handpumps by recording hourly water volume abstracted. Data from April 2019 to October 2021 for 26 of these sites, alongside qualitative data, were analysed and each handpump’s contribution to year-round water security was explored, focusing on the long dry season when water supply from other sources is compromised. Abstraction was over 20 times higher in the long dry season than in any other season, and at sites with higher salinity, higher livestock use, and larger dam wall area. At 21 wells, abstraction was still being recorded at the end of at least one long dry season; however, high spatial and temporal heterogeneity between pumps and seasons means that not all sand dams deliver reliable water supply year-round. Quantifying the contribution that sand dams make to water security is crucial for understanding their resilience against a changing climate and can aid decision makers when choosing the most appropriate water management technique. Knowledge of temporal and site heterogeneity in abstraction can inform when other water sources need increasing and can help with sand dam design optimisation. Overall, our results indicate the positive contribution that sand dams make to year-round water security through the water that is abstracted through handpumps.The online version contains supplementary material available at 10.1007/s10661-023-11694-9. Drylands, or arid regions, are home to one-third of the world’s population but face severe threats to water security, resulting in a deficit between supply and demand , long rains (March–May), long dry (June–September), and short rains (October–December) . The WDT consists of an integrated-circuit-based accelerometer, a microprocessor, and a GSM  modem  via the GSM modem  a strong cellular network signal so that the accelerometers can transmit data (which are converted to abstraction volume) through the mobile network and (2) the handpumps being used daily in order to provide continuous data Chan, . ASDF vir>0.7 and r>0.5 respectively. Although CHIRPS data is less accurate in dry than moist conditions, with light precipitation events found to be underestimated and heavy precipitation events overestimated, it has been found to be more suitable than other products for small-scale studies  resolution infra-red satellite data to estimate daily precipitation ), distance (average distance of round trip to handpump (km)), and user numbers. These were analysed using two models to provide insight into differences in abstraction between sites.Variables collected in fieldwork included perceived salinity , abstraction limits , livestock use (% of interviewees using the handpumps for livestock), whether the dam is said to have ever run dry, presence of rainwater harvesting tanks (% of interviewees with tanks), and actual salinity (μs/cm). These variables were chosen based on knowledge regarding possible reasons for the use of such wells Chan, . VariablThe rainfall data was analysed in Google Earth Engine  was differentiated from missing data, which was represented by NA or an excluded data point. The raw hourly data was collated into daily, weekly, monthly, and seasonal data for the analysis.To analyse patterns of abstraction, daily, monthly, and seasonal (L/day) data sets were used. All data were used, apart from four outliers at Wikwatyo of >14,000L/day which were removed where necessary for clarity in figures.To analyse the relationship between sand dam characteristics and abstraction volume, median monthly abstraction per person (L/person/day) was used. Only handpumps with data for all variables in the models were included.To analyse abstraction patterns in the long dry season, median weekly abstraction per person (L/person/day) was used. Only handpumps with >4 days’ worth of data available for the last week of September in at least 1 year were used.To account for the missing data, all days with any missing hourly data were excluded so that total daily abstraction was based on a complete day. Following this, specific inclusion criteria were developed for different abstraction data sets depending on the analysis:These data sets were used to assess the contribution that each handpump was making to year-round water security. The data were coded and analysis performed in R Studio . Following a detrending of the data, total monthly abstraction was compared to total monthly rainfall at each site, using Spearman’s rank correlations (non-parametric version of a Pearson test), to assess whether monthly abstraction varies significantly with rainfall.p) independent predictors of outcomes were assessed at p < 0.05, <0.01, and <0.001. The first model included the independent variables: month, site, actual salinity, area of dam wall, livestock usage, abstraction limits, and the proportion of interviewees with a RWH tank. The second model additionally included distance. These variables were chosen for exploration purposes and due to previous research findings . VariabFinally, analysis in the last full week of September (end of the long dry season) assessed whether handpumps were providing at least sufficient drinking water by this point. Due to the necessity of an improved source of water for drinking, the handpumps were classified based on a median weekly abstraction of 2L/p/day and 4L/p/day in the final full week of September, based on the minimum drinking water requirement cited by the World Health Organisation  in regulAverage monthly rainfall across the 26 study sites for the duration of the study period (April 2019–October 2021) displayed the recognised Kenyan trend of two rainy and two dry seasons. Long-term average yearly rainfall across the 26 study sites from 1981 to 2021 was 760mm. Yearly rainfall for 2019, 2020, and 2021 was 1035mm, 996mm, and 726mm, respectively, highlighting 2019 and 2020 as wetter than average CHIRPS, .However, on a seasonal level (based on literature derived seasons), the long rainy seasons in 2019 and 2021 were drier (160 mm and 264 mm respectively) than the long term average (286 mm), whilst 2020 was wetter (438 mm). This is in comparison to the short rainy season, which in 2019 was over two times greater (797 mm) than the average (375 mm), whilst 2020 and 2021 were slighlty drier (332 mm and 369 mm respectively) CHIRPS, .n=840 counts of 0L abstraction, whilst most values  lay between >0 and 250L/day.Across the months in which each handpump transmitter was live, the amount of missing daily data ranged from 5.8% at Woni 15 to 75.4% at Woni 16. Seven handpumps had >50% of data missing, whilst twelve had <25% of data missing. Not all transmitters were operational from April 2019 to October 2021, making it an unbalanced data set. The data set of daily abstraction showed a non-normal distribution, with a high positive skew to the right . Of 11,610 data points, there were n=17)     Fig. A, whilst=5) Fig. B. Others11) Fig. C, whilst) Fig. n=  Fig. .Fig. 3Dap = 0.0145) difference in median daily abstraction between seasons (L/day) amongst individual sites.Handpump use was heterogenous between seasons Figs.  and 6. Wr=.45, p=0.038), Kithunthi , Mapatano 17  Mbukilye , and Wendo , with the four latter sites indicating significantly higher monthly abstraction when rainfall is lower. Most of the other sites also show negative correlations, as shown in Fig. Median monthly abstraction averaged across all sites showed a peak in the long dry season . There is generally a decreasing trend in abstraction towards the end of the long dry season in 2019 and 2020. Lower levels of abstraction were observed throughout the rest of the year, with the lowest occurring at the end of the short rainy season in 2019, in the short dry season in 2020, and at the end of long rainy season in 2021 Fig. . SpearmaIn order to assess whether any sand dam characteristics or individual behaviours were influencing abstraction, two random effects regression models were used. Table Data on five of the independent variables of sand dam characteristics or individual behaviours Table : actual This first model explained 47.1% of the variation in abstraction (28.1% within and 100% between). Within variation represents the total variation in the individual values in each group and their group mean whilst between variation represents the total variation between each group mean and the overall mean.Except for September 2019, June 2020, and July 2020, 75% of the long dry months during the 3 years were found to have significantly higher abstraction than the reference month of January 2020.Abstraction was also significantly higher in the rainy seasons of May 2019, Oct 2020, and October 2021. Sites where actual salinity was higher, dam wall area was larger, and more people were using the water for livestock had significantly higher levels of abstraction. Abstraction limits and the proportion of people with RWH tanks were not significant.Distance was included in a second model, using the reduced number of handpumps Table . Ever ruOf the 26 handpumps, 22 had abstraction data available for the last full week of at least one long dry season (September), with 21 having some water abstracted, indicating that they were providing water when access to other sources may have been compromised. Median daily abstraction in this week averaged across the 3 years across the 22 sites was 242L. This varied, however, between 0L at Bodeni and 5920L at Kee 13.N=7) of sites were classed as providing sufficient water (>2.3L/p/day) by the end of each long dry season (2019–2022) for which they have data available: able to meet users’ minimum drinking needs. A further 27.3% (N=6) met this need by the end of at least one long dry season for which they have data available. Of these 13 handpumps, 84.6% (N=11) were providing >4.6L per person: the drinking water needs in hot climates  were not providing sufficient water (<1.7L), failing to meet the drinking water needs of their users in any year  still had >2.3L being abstracted when using a household size of 6.15  from the sand dam handpumps from the short dry to the long dry season. Neufeld et al.  found abThe results show high heterogeneity in abstraction between handpumps, with median daily abstraction ranging from 2 to 2962L. Possible reasons for this heterogeneity include water availability due to sand dam characteristics, including area of wall, grain sizes, depth of sediment, width of riverbed, and slope of banks  of samples exceeded. People often seek alternative sources to using saline water for drinking . The WHO  permissi2 and above , indicating a contribution to year-round water security. This is consistent with Hanson and Nilsson  who citeThe results from Table The variation in abstraction between years shows that whilst some handpumps can provide 2L/person/day, other factors may be impacting abstraction such as the availability of other sources, population numbers which may not remain stable, variable rainfall rates, and the maturity of the dam. The lack of data for some sites also means that further conclusions cannot be drawn.Whilst sites were selected due to a known reasonable signal, across the period that each transmitter was live there is some missing data. Uneven proportions of missing data in different seasons and sites place limitations on the comparisons that can be made between sites and time periods. This is an inherent challenge in certain, especially rural settings across the world. This study in part overcame this uncertainty by using average values and developing exclusion criteria. It can also be argued that the benefits of using WDT over or in coordination with traditional methods of data collection outweigh the uncertainties. Using this data, the study has positively contributed to the literature on sand dams. Whilst there is heterogeneity in abstraction between seasons and sites, many handpumps are still being used by the end of the long dry season, with significantly more abstraction seen at sites with higher salinity, larger dam walls, and higher livestock usage. Sand dams can therefore be seen as an effective dryland water source, especially useful in the dry season.As the first study to analyse multi-year abstraction trends from sand dam handpumps, it reveals, quantitatively, the positive contribution that sand dams can make to year-round water security, by providing a water source by the end of the long dry season when other water sources are compromised. Of 22 handpumps with abstracted data for the end of at least one long dry season, 59.1% suggest they can meet drinking water needs by the end of the long dry season independently of other sources.Having said this, heterogeneity in abstraction is a reminder that not all sand dams behave the same, with certain sand dams always likely to have higher levels of abstraction than others, such as those with higher user numbers, levels of salinity, livestock use, and larger dam walls. The findings of low abstraction from certain handpumps and in certain months challenge sweeping statements in literature professing the success and perfection of all sand dams, which are neither accurate nor helpful. Yet, as abstraction levels are not synonymous with water storage in the dam, with many confounding factors impacting level of abstraction, without further research, their true capabilities are unknown. High abstraction and sustained water availability by the end of the long dry season at many sites profess the positive contribution that sand dams can make to a community’s water supply, offering opportunities for further success in the future.ESM 1(DOCX 180 kb)


To determine whether Twitter improves dissemination of ophthalmology scientific publicationsData were collected on articles published on PubMed between the years 2016 and 2021 (inclusive) and identified with the word “ophthalmology”. Twitter performance metrics, including the number of tweets, number of likes, and number of retweets were collected from Twitter using the publicly available scientific API. Machine learning and descriptive statistics were used to outline Twitter performance metrics.The number of included articles was 433710. The percentage of articles that were in the top quartile for citation count, which had ≥1 tweet was 34.4% (number 437/1270). Conversely, the percentage of articles that were in the top quartile for citation count, which had 0 tweets was 27.8% (number 12023/43244). When machine learning was used to predict Twitter performance metrics an AUROC of 0.78 was returned. This was associated with an accuracy of 0.97This study has shown preliminary evidence to support that Twitter may improve the dissemination of scientific ophthalmology publications. Dear Editor,Ophthalmic practitioners, researchers and journals  use Twitter to share and discuss peer-reviewed scientific ophthalmology publications –4. UsersData were collected on articles published on PubMed between the years 2016 and 2021 (inclusive) and identified with the word “ophthalmology”. Twitter performance metrics, including the number of tweets, number of likes, and number of retweets were collected from Twitter using the publicly available scientific API. Tweets were included that used the term "pubmed.ncbi.nlm.nih.gov". Tweets were linked to individual articles with PubMed ID.Descriptive statistics were used to outline Twitter performance metrics. Wilcoxon signed rank tests  and chi squared tests were used to compare article characteristics with respect to title length, abstract length, and number of authors. Data underwent pilot machine learning analysis to gauge whether a signal were present in the prediction of Twitter performance metrics. Namely, text  underwent pre-processing , and were then randomly split into training and testing datasets (75%/25%). A XGBoost was then developed on the training dataset, prior to evaluation on the holdout test dataset, aiming to predict whether any given article would receive ≥ 1 tweet or no tweets. This model was chosen due to the imbalanced nature of the dataset. The primary outcome was the area under the receiver operator curve (AUROC). This study did not require institutional ethical approval due to the use of publicly available data.The number of included articles was 433,710. The number of articles which had ≥ 1 tweet identifiable was 1270 (0.29%) . It can be seen that these performance characteristics need to be viewed in the context of an unbalanced test dataset.This study has shown preliminary evidence to support that Twitter may improve the dissemination of scientific ophthalmology publications. We report that scientific ophthalmology publications with higher performance on Twitter metrics, namely having at least one tweet, may be associated with higher performance on conventional academic metrics such as citations. It is important to note the observational and retrospective nature of this analysis. We recgonise that the “black box” nature of machine learning lessens interpretability, and that reverse causality may account for the study findings by producing a biased model. Further studies may seek to trial engagement with social media in a randomised manner to gauge whether such activity influences the scientific impact of articles. Continued work in this field may also explore the effect of the dissemination of false or misleading ophthalmic research findings through Twitter, a topic of growing concern .


When drilling into a reservoir, the drilling fluid containing bentonite is prone to solid phase invasion, causing serious damage to the reservoir, and the conventional API barite suspension stability is poor, which makes it easy to cause sedimentation and blockage. Therefore, in order to avoid accidents, we use ultrafine barite to obtain a good suspension stability. More importantly, the method of modifying zwitterionic polymers on the surface of nano-silica is used to develop a temperature-resistant and salt-resistant fluid loss reducer FATG with a core-shell structure, and it is applied to ultra-fine clay-free water-based drilling fluid (WBDF). The results show that the filtration loss of clay-free drilling fluid containing FATG can be reduced to 8.2 mL, and AV can be reduced to 22 mPa·s. Although the viscosity is reduced, FATG can reduce the filter loss by forming a dense mud cake. The clay-free drilling fluid system obtained by further adding sepiolite can reduce the filtration loss to 3.8 mL. After aging at 220 °C for 15 d, it still has significant salt tolerance, the filtration loss is only 9 mL, the viscosity does not change much, a thinner and denser mud cake is formed, and the viscosity coefficient of the mud cake is smaller. The linear expansion test and permeability recovery evaluation were carried out. The hydration expansion inhibition rate of bentonite can reach 72.5%, and the permeability recovery rate can reach 77.9%, which can meet the long-term drilling fluid circulation work in the actual drilling process. This study can provide guidance for technical research in related fields such as reservoir protection. When drilling into a reservoir, solid phase invasion will cause damage to the reservoir. Clay-free drilling fluid technology, solid-free drilling fluid technology, shielding temporary plugging technology, non-permeable drilling fluid technology, and underbalanced drilling technology can be used for reservoir protection . ShieldiClay-free drilling fluid is usually composed of water-phase and solid-phase particles . The watThe exploration and exploitation of modern oil and gas resources will be carried out in deep or ultra-deep strata . Filter Here, we systematically studied the filtration performance of FATG and ultrafine barite mud cakes in terms of filtration loss and mud cake quality by comparing different formulations of clay-free drilling fluids. This can not only prevent the drilling fluid from flocculation when working in the wellbore, maintain the stability of the wellbore, reduce the resistance, and improve the penetration rate, but also increase the application range of salt and temperature resistance compared with the previous working fluid. It is of great theoretical and practical significance to improve the level of reservoir protection technology and promote the technological progress of some special wells such as horizontal wells and extended reach wells.FATG is produced by our group. Other required materials are shown in 2 was dispersed in deionized water by ultrasonic technology, and then a certain amount of MPS and a few drops of NH3-H2O were added. The mixture is then transferred to a three-port flask containing a mechanical stirrer and a reflux condenser. After that, the mixture was heated to 50 °C and stirred at 500 r/min for 48 h in a nitrogen atmosphere. After removing the supernatant, the prepared product was centrifuged, washed 2–3 times with anhydrous ethanol, and dried in an oven at 70 °C for 48 h. The intermediate product MSiO2 was obtained. In the second part, MSiO2 was dispersed in deionized water, and then 1-Acrylanmido-2-methylpropanesulfonic acid (AMPS) was added. The pH of the mixture was adjusted to 7~8 by sodium hydroxide, and then diallyl dimethyl ammonium chloride (DMDAAC), N-Vinyl-2-Pyrrolidinone (NVP), and initiator potassium persulfate were added in turn. The mixture was transferred to a flask, nitrogen was introduced to remove oxygen, and it was heated at 70 °C for 5 h to obtain the final product FATG [The synthesis of FATG can be divided into two parts. In the first part, SiOuct FATG ,22.3 g/cm3 and dropped on the surface of copper grid and dried naturally before measurement [The microstructure of FATG was observed using transmission electron microscopy . FATG sample was diluted to a concentration of 10surement .−1.The chemical structure was analyzed by Fourier infrared spectroscopy  in the −1 in the temperature range of 25−600 °C.The thermal stability of FATG was investigated using a thermogravimetric analyzer  for 20 min. Then, FATG, sepiolite powder, butadiene latex, and GBG were added at certain ratios and stirred for 20 min. NaCl and KCl at a ratio of 7:3 were added, and stirred for 20 min .According to the American Petroleum Institute (API) criteria, the filtration performance of the newly prepared fluid and the aged fluid was determined. About 250 mL of liquid was poured into a standard API filter device  equipped with an enhanced filter paper with a diameter of 90 mm and a pore size of 2–5 μm. The filtration test was carried out under the pressure difference of 0.7 MPa with nitrogen gas for 30 min. The filter volume was recorded, and the mud cake was naturally dried at ambient temperature after each measurement.Platinum was sprayed on the surface of the sample in advance, and the microstructure of the dried mud cake was observed by scanning electron microscope .In order to measure the rheological parameters at room temperature, a six-speed rotational viscometer  was used at a selected shear rate, and the viscosity was recorded every 5 min to provide an approximately stable reading. Four values are recorded continuously. If the difference between the arithmetic mean of the last three values and the first value is less than 5%, the viscosity value of the shear rate is considered to be determined.According to the principle of oil drilling fluid engineering , the relThe gel strength (Gel) indicates the strength of the spatial network structure formed by the drilling fluid, and reflects the shear force required to destroy the network structure in the internal area of the drilling fluid when the drilling fluid is stationary. The calculation formula is as follows:10 s indicates the static shear force value measured by the drilling fluid after sufficient agitation and resting for 10 s, which is the initial shear force, and τ10 min indicates the static shear force value measured by the drilling fluid after sufficient agitation and resting for 10 min, which is the final shear force.In the formula, τPour the drilling fluid into the densimeter , load until there is a trace of drilling fluid overflow, slide and move the scale to keep it balanced, and then read. Three density tests were carried out continuously, and the average value of the three density tests was taken as the final density.The inhibitory effect of FATG soil-free phase drilling fluid and its filtrate on the swelling of artificial cores at three salt concentrations was evaluated by using a dual-channel linear swelling meter  . The speThe sticking factor of mud cake of FATG clay-free drilling fluids at three salt concentrations was determined by using a sticking factor of mud cake meter . The specific steps were to adjust the slide plate and balance foot of the meter to keep the water bubble centered and zeroed. The drilling fluid mud cake was placed flat on the sliding plate and the slider was placed longitudinally on the mud cake and left for 1 min. Then, the start button was pressed to make the sliding plate rotate slowly. When the slider starts to slide, stop the instrument, at this time, the value in the display window is the mud cake friction angle, and the unit is °. Check the tangent of its display angle value; the tangent value is the sticking factor of mud cake .0. The cores were contaminated with two soil-less phase drilling fluids for 125 min at room temperature, constant pressure of 3.5 MPa, and constant shear rate of 170 s−1, respectively. The final contaminated core gas permeability was measured and recorded as K1. The permeability recovery rate recorded as R could be calculated by the following equation [0 is the initial gas permeability in mD; and K1 is the contaminated core gas permeability in mD.Sirrine et al.  introducequation :(5)R=K1KThe turbidity of formation water mixed with different ratios of drilling fluid filtration loss liquid was determined using a turbidimeter . The specific steps were to turn on the instrument and warm up for 30 min, toggle the switch to the measurement place, and zero the instrument. Slowly inject about 50 mL of the tested sample. Clean the sample cup with filter paper and place it into the colorimetric cell, and cover the inner lid of the colorimetric cell. After the data is stabilized, the turbidity value of the tested solution can be read.From the TEM photos a, it can−1 and 1545 cm−1, and the antisymmetric absorption peak of -CH3 appeared at 2935 cm−1. The absorption peaks appearing at 1463 cm−1 are amide groups in -CONH2, while the absorption peaks at 1042 cm−1 and 628 cm−1 are from the antisymmetric stretching vibration of -SO3-, according to the analysis of the synthesized feedstock. The appearance of these peaks also represents the composition of the FATG macromolecular structure. In addition, the presence of the Si-O-Si group in the synthesized raw material influences the formation of the stretching vibration peaks at 768 cm−1 and 523 cm−1 in this IR spectrum; in addition, the correlation of the mass of FATG with temperature was measured by the thermal weight analysis technique, and the temperature and salt resistance mechanism were analyzed based on these two analysis techniques. The results are shown in According to the analysis of the FTIR results in According to the TGA analysis in −3. Compared with conventional API barite, micro barite has a small size and large specific surface area; thereby, it has a better settling stability. Then, 8 g of stabilizer and 16 g of dispersant were added into the clay-free drilling fluids to stabilize the micro barite. Four filtration reducers including soluble GBG, nanomaterials including FATG, sepiolite, and butadiene latex were used. In this section, the rheological property measurements, API filtration loss measurements and density measurements of the 15 formulations were carried out to compare and evaluate the overall performance.In this study, 750 g ultra micro barite powder was added to obtain a drilling fluid with a density of 2.1−2.3 g cmSepiolite has good thermal stability and rheology, and can be used as a fluid loss reducer or tackifier in drilling fluid. Therefore, we first evaluated the filtration performance of FATG and sepiolite alone and in combination. The test result data are shown in Considering a saline environment is beneficial to reducing water activity, we mitigate the water reflux into the formations under osmotic pressure, which is very important for stabilizing the wellbore and protecting the reservoir from damage. Then, 10% salt was added into each drilling fluid  to studyWhen 10 wt.% NaCl and KCl was added, the viscosity of drilling fluids containing FATG or sepiolite increased significantly. This may be due to the fact that, when the particle content increases, the particles accumulate tightly, the spacing decreases, the free movement of the particles becomes difficult, and the interaction force between the particles increases, resulting in a larger flow resistance; that is, the viscosity increases.From the perspective of fluid loss reduction performance, when no fluid loss reducer is added, the filtration loss reaches more than 10 mL, and the butylated latex shows poor filtration control ability, and the filtration volume reaches 22.4 mL after only 3 min. In comparison, the drilling fluid with FATG has the best filtration performance before and after aging, and the drilling fluid with sepiolite also has higher shear force, which is beneficial to maintaining the relative stability of nano-barite in the drilling and completion process and reducing the operation risk. However, FATG exhibits better filtration performance due to the polymer coverage on silica, which is more suitable for filtration performance.In view of the fact that GBG exhibits good fluid loss reduction performance and exhibits similar rheological properties to FATG, in order to illustrate the superior fluid loss reduction ability of FATG, the combination of GBG and GBG with sepiolite was investigated in a drilling fluid containing 10% NaCl and KCl. The results are shown in In view of the performance of the unaged formula in rheology and filtration evaluation, in order to highlight the effect of FATG after high-temperature aging, we preferably tested the performance of drilling fluid aged at 180 °C for 16 h . After aAccording to the above results, it can be concluded that the drilling fluid containing FATG still has good filtration performance even after aging at 180 °C for 16 h. On this basis, the filtration performance of hot rolling after different times was measured. Because the aging time required in this experiment is prolonged, we only pre-added 5 wt.% NaCl and KCl into the drilling fluid. It is worth noting that the FATG content increases or FATG is combined with sepiolite . CompareThe viscosity of the drilling fluid with only FATG increased slightly to 35 after hot rolling for 5 d, and then the viscosity remained stable. It is conducive to the safety of the drilling process. The filter loss decreases first and then increases with the aging time (5–15 d). The API filtration loss of all samples was less than 8 mL, showing excellent anti-aging properties. When sepiolite is added, the viscosity increases before hot rolling and decreases after hot rolling, which is different from that without sepiolite.In order to test the performance of clay-free drilling fluid with FATG and sepiolite as a filtrate reducer after 15 d of high-temperature aging at 220 °C, we only added 3 wt.% NaCl and KCl in advance. The rheological properties and filtration loss were tested before hot rolling and after hot rolling for 5 d, 10 d, and 15 d, respectively. The experimental results are shown in From The mud cakes of FATG and sepiolite clay-free drilling fluid were studied by the filtration loss test of API barite powder and ultrafine barite powder . The resIn order to evaluate the inhibition of clay-free WBDFs containing FATG on bentonite, we measured the swelling height of the artificial bentonite core in the clay-free system and its filtrates with different NaCl and KCl concentrations, and the results are shown in We also carried out experiments on the filtrate of three groups of systems . The linIn order to evaluate the frictional resistance of clay-free WBDFs containing FATG when the drill string moves or slides along the surface of the mud during practical application, we tested the mud cake adhesion factor of clay-free drilling fluid at three salt concentrations. The results are shown in In order to demonstrate the excellent reservoir protection effect of FATG-containing clay-free WBDFs, we tested the effect of clay-free drilling fluid Code15 on core permeability under the condition of FATG addition as a variable, and the results are shown in In order to ensure the reservoir protection effect of the drilling fluids, we conducted a formation water compatibility test on the drilling fluids containing FATG. The drilling fluid filtrate of Code 15 and the formation water of the Upper Urho Formation in the Mahu Block in Xinjiang, China were selected for the test, and the composition of the formation water is shown in According to In this study, a new type of ultra-fine clay-free drilling fluid formula with the significant advantages of temperature resistance and salt tolerance was developed by mixing the self-developed product FATG with sepiolite and using ultra-fine barite to increase density. It has good fluid loss reduction, suspension, rock-carrying capacity, thermal stability, inhibition and lubricity, and a low viscosity coefficient of its mud cake, and retains the advantages of high-performance water-based drilling fluid. It can effectively improve the drilling speed and prevent solid and liquid phases from invading the reservoir, and improve the reservoir protection ability of the drilling fluid. The optimized clay-free drilling fluid permeability recovery rate is reliable. The addition of the fluid loss reducer FATG makes the formed mud cake denser, increases the hydrophobicity of the mud cake, and prevents the drilling fluid from settling and the liquid phase from invading the reservoir. Therefore, the final optimized FATG clay-free drilling fluid can still maintain a good fluid loss reduction effect after a long period of high-temperature aging, and, as the drilling fluid circulates in the wellbore for a longer period of time, the viscosity gradually decreases, avoiding the phenomenon that the viscosity increases due to the long drilling time, which, in turn, causes the sticking phenomenon. The research results can provide a reference for the development of high-temperature and high-salt drilling fluid for special wells such as horizontal wells and extended reach wells, and the solution of other similar problems.


AC tumour samples had a higher SFRP1 level than NT samples (p = 0.022), while the highest SFRP1 concentration was found in NSCLC samples from patients with clinical stage T4 cancer. Increased concentrations of SFRP1 and SFRP5 were present in stage III NSCLC samples, while the tumour samples with high pleural invasion (PL2) had an increased level of SFRP2. The results from this study suggest that the tumour suppressor or oncogenic roles of SFRPs could be connected with the NSCLC subtype. The levels of SFRPs varied according to the clinicopathological parameters of NSCLC. Non-small cell lung carcinoma (NSCLC) is the most common lung cancer worldwide. Secreted frizzled-related proteins (SFRPs) are important tumour suppressors and antagonists of the Wnt signalling pathway, which is linked with cancer development. The aim of this study was to evaluate the concentrations of SFRP1, SFRP2, and SFRP5 proteins in tumour and non-tumour (NT) samples obtained from 65 patients with primary NSCLC. An enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of SFRPs in the tissue homogenates. A significantly lower SFRP2 protein concentration was found in the total NSCLC tumour samples and the following NSCLC subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (AC) ( Lung cancer is the most common cancer, affecting 1.8 million people worldwide each year. It is one of the most aggressive malignancies, with a 5-year survival rate of about 22% ,4. The dThe Wnt signalling pathway participates in the regulation processes related to embryogenesis and cell proliferation and differentiation ,17. GlycSFRP1 is the most researched molecule of all the SFRP family proteins, and its tumour suppressor activity has been well established in various types of cancer, such as intrahepatic cholangiocarcinoma and cutaneous squamous cell carcinoma ,23,24. AChanges in the mRNA expression of SFRPs have been found in multiple cancers, including lung cancers, and have been associated with cancer risk and prediction . In seveThis is the first study to evaluate the concentrations of SFRP1, SFRP2, and SFRP5 in tumour and non-tumour (NT) samples from patients with primary NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The possible associations of clinical and demographic variables with the concentration of the selected proteins in the Polish population were also analysed.The study population comprised 65 patients recruited from the Department of Thoracic Surgery, Faculty of Medical Sciences, Zabrze, Medical University of Silesia in Katowice. Inclusion criteria were a diagnosis of NSCLC and consent to participate in the study. The exclusion criteria were a diagnosis of lung cancer other than non-small cell lung cancer and a lack of patient consent to participate in the study. All patients were diagnosed via computed tomography (CT)-guided lung aspiration biopsy. In total, 65 tumour and non-tumour (NT) samples were obtained during surgical resection. The tumour samples contained histopathologically confirmed NSCLC cells. The NT samples were taken from macroscopically unchanged tissue at >3 cm distance from the tumour, and the presence of cancerous cells was excluded by pathologists. All tumour and NT samples were immediately frozen at −75 °C until homogenisation. All patients underwent R0 resection and no STAS (spread through air spaces) were found. The tumour stage was evaluated according to the 8th edition of the TNM classification . This stThe methodology for homogenisation was presented in a previous study . The tumThe methodology for protein concentration analysis was presented in a previous study . An enzyThe methodology for protein concentration analysis was presented in a previous study . The quat-test or the Mann–Whitney U test was used to verify the significance of differences in means or medians between groups. The correlation was determined with Spearman’s rank correlation coefficient. The level of significance was set at p < 0.05. Results are presented as mean ± SD or median with quartile range. Analyses were performed using Statistica 13.1 .Results were tested using the Shapiro–Wilk test to determine the normality of the data. Student’s The study group consisted of 65 patients with confirmed non-small cell lung cancer. The mean age was 69.09 (±7.13) years. Forty-seven (72.30%) patients admitted to smoking tobacco products. The characteristics of the study group are presented in The absence of distant metastasis was determined using imaging techniques, such as computed tomography (CT) and positron emission tomography/image-based computed tomography (PET/CT). As a result, this group of patients was homogeneous in parameter M (a component in the TNM classification). In patients with enlarged mediastinal lymph nodes, found through imaging studies, endobronchial/endoscopic ultrasound (EBUS/EUS) was performed. The final pathology TNM (pTNM) classification was determined through the postoperative histopathological examination of resected tumour samples.p < 0.001). No statistically significant differences were found in the protein levels of SFRP1 or SFRP5 between tumour and NT samples, but their median concentration was slightly higher in the tumour samples. The concentration levels of SFRPs are presented in Analysis of the total NSCLC group showed significantly lower SFRP2 protein concentration in tumour samples than in the NT tissue (189.45 vs. 614.22) , while the level of SFRP2 protein was reduced in tumour samples (p < 0.001). For the AC subtype, significantly higher concentrations of SFRP1 and SFRP5 in tumour samples compared to NT were detected (p = 0.028). However, the levels of SFRP1 and SFRP5 were not significantly different between tumour and NT samples (p > 0.05). For the SCC subtype, a lower SFRP2 concentration in tumour specimens than in NT was observed (p > 0.05).For the LCC subtype, no significant differences in the levels of any analysed SFRPs were observed between tumour and NT samples (p = 0.021) and AC  tumour samples, respectively. The results are given in Comparisons between NSCLC subtypes showed a significantly higher level of SFRP2 in LCC tumour samples compared to SCC  and AC  NT samples, respectively, was observed. The results are presented in p = 0.0.28, and SFRP5: 5995.4 vs. 2512.5 p = 0.003), respectively, were observed. No other differences in levels of any analysed SFRPs between NSCLC subtypes for NT samples were found.Similar to the results for the tumour samples, in NT, an increased level of SFRP2 in LCC samples compared to SCC , T2 vs. T4 , and T3 vs. T4 , respectively. Moreover, the level of SFRP1 was significantly higher in tumour samples obtained from patients with stage III NSCLC compared to tumour samples obtained from patients with stage II . The results are given in p > 0.05). SFRP1 protein concentration was significantly higher in tumour samples from patients with clinical stage T4 compared to NSCLC samples with other T parameters: T1 vs. T4  (p = 0.233), as well as PL0 and PL2 (p = 0.640). No significant association between the level of SFRP2 protein and parameters, such as T, N, G, tumour stage, sex, and smoking, was observed (p > 0.05). Significantly higher SFRP2 protein levels were found in the tumour samples collected from patients with pleural invasion PL2 in comparison to the patients with PL1 NSCLC  . The SFRp = 0.042). The results are shown in Higher SFRP5 protein concentrations were observed in tumour samples with stage III compared to stage I NSCLC  was found in tumour samples. p = 0.047; rS = 0.269) and stage .No statistically significant correlations between the concentrations of the selected proteins and any of the analysed clinical and demographic parameters were found. Moreover, the T parameter positively correlated with pleural invasion (The SFRP family is involved in regulation of the WNT signalling pathway, which is linked with cancer development . The rolSFRP1 expression found significantly decreased SFRP1 gene in tumour tissues compared to normal counterparts, in various cancers [SFRP1 has been associated with poor prognosis in lung squamous cell carcinoma and correlated with a better prognosis for patients with other types of cancer, including breast carcinoma, oesophageal adenocarcinoma, or head and neck squamous cell carcinoma [SFRP1 mRNA levels correlated with different prognoses for patients with lung adenocarcinoma depending on the datasets used [In this study, a significantly higher concentration of SFRP1 was found in the tumour samples compared to NT samples among patients with adenocarcinoma. On the other hand, the concentration of SFRP1 was insignificantly higher in SCC tumour samples and insignificantly lower in LCC tumour samples compared to NT samples. Moreover, higher concentrations of SFRP1 in NT samples collected from patients with SCC compared to AC was found. Importantly, in the literature, the level of SFRP1 was different for various cancers. A study based on breast cancer cell lines reported that SFRP1 protein level varied according to breast cancer subtype . A decre cancers , suggest cancers . The higarcinoma . Interesarcinoma  revealedets used . Moreoveets used . Conversets used . It has ets used . TherefoSFRP2 is a tumour suppressor in various cancers and an important suppressor for NSCLC invasion ,49,50. ISFRP5 mRNA was associated with a better prognosis [SFRP5 gene in different primary tumours, including lung adenocarcinoma and lung squamous, compared to normal tissues [SFRP5 gene was significantly higher in tumour samples than in normal tissues, and the authors suggested the oncogenic role of SFRP5 in lung adenocarcinoma [In this study, in patients with adenocarcinoma, a significantly higher concentration of SFRP5 was observed in tumour than in NT samples. Interestingly, it was observed that, in the total NSCLC group, an increased level of SFRP5 was present in tumour samples obtained from stage III NSCLC patients compared to stage I. In the literature, the SFRP5 protein concentration in cancers is still not explored enough. The antagonist role of SFRP5 in the canonical and non-canonical Wnt signalling path has been confirmed in breast cancer, where a higher level of rognosis . A reducrognosis ,54. More tissues . Conversarcinoma . LikewisSFRPs are not well studied regarding NSCLC; therefore, further studies are required to understand the connection between changes in SFRP concentrations and clinical and demographical parameters. The small sample size is the main limitation of this study. Our results should be validated on larger and more diverse cohorts. Moreover, further studies are needed to verify the impact of changes in SFRPs concentrations on the survival rate and prognosis in patients with NSCLC subtypes. In conclusion, this study found changes in selected SFRP concentrations in tumour samples and non-tumour samples, in patients with NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. These findings suggest that the tumour suppressor or oncogenic roles of SFRPs could be connected with the NSCLC subtype. In addition, we noted that SFRP levels varied according to clinicopathological parameters of NSCLC. Further studies are needed to verify how changes in SFRP concentration may affect tumour development and prognosis for patients.


ECMO provides life-saving cardiac and/or pulmonary support to critically ill patients, but its effects on the PK of many antimicrobials remain unknown. Herein, we describe the PK of imipenem (IMI) and relebactam (REL) in critically ill patients supported on ECMO.fAUC/MIC ≥ 8 and IMI ≥ 40% fT >MIC was assessed using 1000 patient Monte Carlo simulations for each labeled dosing regimen across CrCL ranges of 15-29, 30-59, 60-89, and 90-130 mL/min.Patients with confirmed or suspected infections supported on veno-venous or veno-arterial ECMO received 4 doses of I/R based on estimated creatinine clearance (CrCL) in accordance with current prescribing recommendations. Blood samples were collected over 6 h after last dose. IMI and REL concentrations were determined by a validated LC/MS/MS assay. Protein binding was assessed by ultrafiltration. Population PK models with and without covariates were fit using the non-parametric adaptive grid algorithm in Pmetrics for R. A joint probability of target attainment (PTA) at steady state using REL 0*(CrCL/113)] fitted the data best. ECMO flow rate did not influence IMI or REL CL. The mean ± SD parameters for IMI were: CL0, 15.21 ± 6.52 L/h; Vc, 10.13 ± 2.26 L; K12, 2.45 ± 1.16 h-1; and K21, 1.76 ± 0.49 h-1. REL PK parameters were 6.95 ± 1.34 L/h, 9.81 ± 2.69 L, 2.43 ± 1.13 h-1, and 1.52 ± 0.67 h-1, respectively. Protein binding for both drugs was 0%. I/R at currently labeled dosing regimens achieved > 90% PTA at the MIC of 2/4 mg/L for CrCL between 15-130 mL/min, supporting efficacy against both Enterobacterales and Pseudomonas aeruginosa.Seven patients  on ECMO received I/R; 1 patient received a single dose of I/R. Mean ± SD age, weight, and ECMO flow rate were 50 ± 16 years, 119 ± 12 kg, and 4.2 ± 0.5 L/min, respectively. Median (range) CrCL were 113 (32-317) mL/min. A two-compartment population PK model using CrCL as a covariate on both IMI and REL CL [CL=CLP. aeruginosa isolates.These are the first data to describe I/R PK in critically ill patients supported by ECMO. For patients treated with ECMO, currently labeled dosing regimens of I/R guided by estimated CrCL are predicted to achieve optimal exposures necessary to treat susceptible Enterobacterales and Abigail Kois, PharmD, AstraZeneca: Sr scientist, clinical pharmacology R&I|AstraZeneca: Stocks/Bonds Jason A. Gluck, DO, FACC, Abbott: Honoraria David P. Nicolau, PharmD, Allergan: Advisor/Consultant|Allergan: Grant/Research Support|Cepheid: Advisor/Consultant|Cepheid: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Tetraphase: Advisor/Consultant|Tetraphase: Grant/Research Support|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support|Wockhardt: Advisor/Consultant|Wockhardt: Grant/Research Support Joseph L. Kuti, PharmD, bioMeriuex Inc.: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Merck & Co, Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|Shionogi Inc: Grant/Research Support|Shionogi Inc: Honoraria


The median apparent dynamic viscosity was 1.63 mPa*s (IQR 1.27–2.09 mPa*s) for serous samples, 2.45 mPa*s (IQR 1.69–3.22 mPa*s) for purulent samples and 3.50 mPa*s (IQR 2.81–3.90 mPa*s) for biliary samples . Relative to water, dynamic viscosities were increased by a factor of 1.36 for serous fluids, 2.26 for purulent fluids, and 4.03 for biliary fluids. Serous fluids have apparent viscosities similar to water, but biliary and purulent fluids are more viscous. These data can be used as a reference when selecting the drainage catheter size, with 8F catheters being appropriate for most percutaneous drainage cases.Percutaneous drainage is a first-line therapy for abscesses and other fluid collections. However, experimental data on the viscosity of body fluids are scarce. This study analyses the apparent viscosity of serous, purulent and biliary fluids to provide reference data for the evaluation of drainage catheters. Serous, purulent and biliary fluid samples were collected during routine drainage procedures. In a first setup, the apparent kinematic viscosity of 50 fluid samples was measured using an Ubbelohde viscometer. In a second setup, the apparent dynamic viscosity of 20 fluid samples obtained during CT-guided percutaneous drainage was measured using an in-house designed capillary extrusion experiment. The median apparent kinematic viscosity was 0.96 mm The effectiveness of this method is well documented in the literature8. Among the various imaging modalities, computed tomography (CT) is preferred by many clinicians for interventional procedures due to its high temporal and spatial resolution. In particular, CT is the modality of choice for deep-seated locations or when fluid collections are surrounded by sensitive structures9. In the absence of guidelines on which catheter size to use, the choice is not evidence-based but based on personal preference and experience. Many physicians prefer larger catheters, but this can increase patient discomfort, procedure time and the risk of complications, such as the need for more dilation of the access tract and an increased bleeding risk10. There is a paucity of scientific data on the relationship between drain size and drainage efficiency, and the suitability of the current drain sizing system has been questioned12. Among other factors influencing the technical success of percutaneous catheter drainage, the viscosity of the fluid and the amount and size of solid particles in the fluid should be considered when discussing the required catheter size. The aim of this study was to analyze the apparent viscosities of the drainage fluid samples obtained and to compare the specific properties with model fluids such as water and glycerol. These measurements can be used as a basis for the selection of drainage catheter sizes as well as for the development and evaluation of new drainage catheters.Image-guided percutaneous drainage is a well-established, minimally invasive treatment alternative to surgical removal of pathological fluid collectionsOf the 50 fluid samples, 31 were classified as serous, 15 as purulent and 4 as biliary (Table 2/s (IQR 0.90–1.15 mm2/s) for serous samples, 0.98 mm2/s (IQR 0.97–0.99 mm2/s) for purulent samples and 2.77 mm2/s (IQR 1.75–3.70 mm2/s) for biliary samples.Of the 15 purulent samples, the capillary of the Ubbelohde viscometer was blocked by debris or solid components in 13 cases and the measurement failed. In the remaining cases, the median apparent kinematic viscosity measured by the Ubbelohde viscometer was 0.96 mmOf the 20 cases included in this study, 11 were classified as purulent, 4 as serous and 5 as biliary , as visualized in Fig. ANOVA with Tukey post-hoc test showed statistically significant differences between the relative viscosities to water of all three fluid types  may be more stable and less prone to kinking and blockage, whereas the stability of catheters depends mainly on the material of the catheter 14. Arguments for smaller drainage tube sizes (7–8 Fr) include improved patient comfort, lower periprocedural complication rates and shorter procedure times 15. Patient comfort is particularly important when the drain is in place for prolonged periods and when the drain is placed dorsally, with the patient lying on the catheter most of the time , or in the liver, which is constantly moving with respiration. In our experiments, most apparent viscosities were only slightly higher than the viscosity of water, suggesting that aspiration should be possible through smaller tubes such as 8 Fr. These results suggest that a standard 8 Fr drain may be sufficient for most body fluid collections and that the technical efficacy of drainage does not necessarily correlate with the internal diameter of the drain. Actively aspirating the fluid, initially and repeatedly throughout the course of the disease, may be of paramount importance to the success of the efficacy of drainage therapy. The measured high apparent viscosity of bile was of particular interest as 6F and 7F catheters have been the standard for biliary drainage in the UK for many years.The experiments in this manuscript were designed to determine the apparent viscosities of biological fluids that are frequently drained in clinical routine. As biological fluids can contain multiple fluid phases and even debris, the results should be considered indicative of the apparent Newtonian viscosities of these different fluids. Taking these considerations into account, the results showed that the median apparent viscosities of purulent and biliary samples were 1.4–2.3 times and 4.0 times the viscosity of water, respectively, while the apparent viscosity of serous fluids was only slightly higher (factor 1.3). This finding may provide a basis for a more evidence-based discussion about the appropriate size of catheter tube for percutaneous drainage. There are a number of arguments for using smaller or larger drainage tube sizes. Some clinicians prefer larger catheter diameters (> 9 French [Fr]), arguing that a larger diameter results in higher flow and therefore better drainage efficacy, particularly for more viscous fluids12. Park et al. compared the time taken to drain 10 ml of different fluids  through different catheter sizes (3–13 Fr). They argue that, according to Poiseuille's law, larger catheters provide faster drainage. Indeed, the time to drain 10 ml of abscess fluid could be reduced from > 800 s with a 4 Fr catheter to 100 s with 7 Fr, 50 s with 9 Fr and < 25 s with 11 Fr and 13 Fr. However, even if the flow rate is higher with larger diameters, there is no evidence that this translates into higher drainage efficacy or a better clinical outcome, as high-flow situations in cavity fluids are rare13. In a clinical context, we do not believe that drainage efficacy is dependent on higher flow rates. In most cases where drains are placed, the fluid collections are either of a certain size (e.g. abscesses) containing a certain amount of fluid—in which case the time to complete drainage is secondary, as long as it is in the range of a few hours—or placed in low-flow environments (e.g. bile)—in which case even small drains have a higher flow than the fluid produced (often few milliliters per hour). In addition, there are certain clinical conditions  where rapid drainage is contraindicated and the use of larger catheters is unnecessary. This is even more important in pneumothorax, as air is approximately 50 times less viscous than water.A study by Gobien et al. supports the hypothesis that drain size has no relevant effect on drain efficiency. Using percutaneous drains of different materials and inner diameters ranging from 5 to 18 Fr, the authors found no significant difference in the success rates of intra-abdominal abscess drainage for the different drain types16. This is consistent with our own clinical experience. In addition, we did not measure the density of the fluid samples, which would have served as an internal control, since the relationship between kinematic and dynamic viscosity depends on density. Finally, we did not perform an experimental setup to directly compare drainage tube sizes with our model fluids; this should be investigated in an additional series of experiments in the future.This study has several limitations. Firstly, some selection bias cannot be excluded, as all samples could have been aspirated through the clinician-placed percutaneous drainage and some more viscous fluids may not have been included. However, the fact that even undiluted glycerol could be aspirated through an 8 Fr drainage catheter (a single experiment performed outside the present study itself) suggests that this potential selection bias does not limit our findings too much. Second, not only fluid viscosity but also the composition of the fluid itself may play a role in drainage efficacy. In this context, the collected fluids may contain several fluid phases and even small debris, therefore we likely measured the apparent viscosities of the collected fluids, which can differ from the viscosity of single-phase fluids. Moreover, single- and multiple-phase fluids can have different rheometric when assuming diverging baseline parameters. Particularly in cases following pancreatitis, fluid collections may contain solid particles or variable amounts of semi-solid necrotic debris, which carry the risk of clogging the catheter. Our study did not specifically look at particle size. A study by Mithöfer et al. showed that primary percutaneous drainage of pancreatic abscesses was successful in only 31% (9/39), but their data suggest that percutaneous drainage can play an important role in the early management of septic and unstable patients by providing early decompression and evacuation of pusIn conclusion, our study provides insight into the apparent viscosities of commonly used drainage fluids and demonstrates that the apparent viscosities of different body fluids are more or less comparable to water. Therefore, larger drainage tube sizes do not necessarily result in better drainage efficacy, but further series of experiments may be needed to clarify the efficacy of different tube sizes.The study protocol was approved by the local ethics committee of the University Hospital of Cologne (IRB 18-243). Informed consent was obtained from all subjects or their legal guardians for inclusion in this prospective study. The study was conducted in accordance with the STROBE guidelines in compliance with the national legislation and the Code of Ethical Principles for Medical Research Involving Human Subjects of the World Medical Association (Declaration of Helsinki).All patients included in this study underwent surgical or CT-guided fluid drainage. All fluid samples were collected during standard clinical procedures performed for valid medical indications. No patient underwent additional procedures to be included in this study. For safety reasons, patients with chronic infections (e.g. HIV and hepatitis) were excluded. The following fluid characteristics were recorded: location, volume, quality  and drainage tube size. Fluid quality was assessed by consensus between the operator performing the drainage and a second consultant (DP and SH). All drainages were technically successful and no patient was referred for re-drainage.CT scans were performed before the intervention using a standardized scanning protocol on a multidetector computed tomography scanner . If a fluid collection was suspected, the drainage tube was immediately placed by an interventional radiologist. In this study, 8 Fr, 10 Fr and 12 Fr side-hole pigtail catheters  were used at the discretion of the interventionalist. The catheter was inserted using the Seldinger technique with an 18 gauge (G) needle for the initial puncture  and a 75 cm, 0.035" guide wire . Flushing of the drainage tubes with saline three times a day was recommended for all tube sizes.Two experimental setups Fig.  were use2/s2; Cannon Instruments, PA, United States)  or from intraoperative drainages during abdominal surgery n = 38) were analyzed. Only samples with at least 20 ml of aspirated fluid were included. The apparent kinematic viscosity of the fluids was measured immediately after collection using a calibrated Ubbelohde viscometer  equipped with a specially designed plunger-capillary system Fig. b. To det4 s−1 and 3 × 104 s−1.The ram speed is varied at a predetermined rate . Under the given conditions, this corresponds to a shear rate between 2 × 10For Newtonian fluids, the Hagen–Poiseuille law can be applied to obtain the fluid velocity from the variation in force measured at a given constant plunger speed.With For the biological fluids, we are aware that deviations from Newtonian behavior can occur, but we estimate the viscosity of the fluids under consideration to be approximately constant in the shear rate regime applied and are aware that we are determining an apparent viscosity. The force developed under constant shear is then determined and plotted against piston speed, and the (apparent) viscosity is calculated from the slope see Fig. . This apFor the second experimental setup, additional fluid samples were collected from 20 patients who underwent CT-guided percutaneous drainage between November 2019 and April 2020. After collection using a 50 ml luer-lock syringe, the samples were stored at room temperature until measurements could be made.p-value of < 0.05 was considered statistically significant.Continuous variables are presented as mean with standard deviation or median and range. Categorical variables are presented as numbers and percentages. Differences between fluid quality groups were assessed by analysis of variance with post-hoc Tukey HSD test. Statistical analysis was performed using R studio version 1.2.5033 (R Core Team 2013). A