Life on the line - Incidence and management of central venous catheter complications in intestinal failure.

BACKGROUND & AIMS: Loss of venous access is threatening for patients with intestinal failure (IF) under long-term parenteral nutrition (PN). We aimed to identify the incidence of central venous catheter (CVC) complications, compare different devices, and analyze interventional recanalizing procedures to restore the patency of occluded CVCs. METHODS: For this retrospective cohort study, patient data from a prospective IF database spanning 16 years was analyzed at a tertiary referral center. Catheter dwell times (CDTs) were distinguished by Kaplan-Meier survival analysis and subgroup analyses were performed for different CVC types (tunneled/port catheters). Specific complications (occlusion, catheter-related infection (CRI), displacement, and material defect) were analyzed. Explantation rates and CDTs were compared. RESULTS: Overall, 193 CVCs in 77 patients with IF under PN could be enrolled (62.524 "CVC-days"). Broviac type "B" was found to be significantly superior to type "A" regarding occlusion, CRI, and material defects (log-rank test: p = 0.05; p = 0.026; p = 0.005 respectively). Port catheters were displaying the highest incidence of CRI (2.13 events/1000 catheter days). Interventional catheter recanalization was performed 91 times and significantly increased the CDT from a median of 131 days (IQR: 62; 258) to 389 days (IQR: 262; 731) (Mann-Whitney-U-test: p= <0.001) without increasing complications. CONCLUSIONS: Different complication rates and CDT were seen depending on CVC type. Tunneled catheters were significantly superior concerning CRI. Interventional catheter recanalization is a viable alternative to fibrinolytics to restore CVC patency, but long-term patency data is scarce.

Emergency critical care: closing the gap between onset of critical illness and intensive care unit admission.

Critical illness is an exquisitely time-sensitive condition and follows a disease continuum, which always starts before admission to the intensive care unit (ICU), in the majority of cases even before hospital admission. Reflecting the common practice in many healthcare systems that critical care is mainly provided in the confined areas of an ICU, any delay in ICU admission of critically ill patients is associated with increased morbidity and mortality. However, if appropriate critical care interventions are provided before ICU admission, this association is not observed. Emergency critical care refers to critical care provided outside of the ICU. It encompasses the delivery of critical care interventions to and monitoring of patients at the place and time closest to the onset of critical illness as well as during transfer to the ICU. Thus, emergency critical care covers the most time-sensitive phase of critical illness and constitutes one missing link in the chain of survival of the critically ill patient. Emergency critical care is delivered whenever and wherever critical illness occurs such as in the pre-hospital setting, before and during inter-hospital transfers of critically ill patients, in the emergency department, in the operating theatres, and on hospital wards. By closing the management gap between onset of critical illness and ICU admission, emergency critical care improves patient safety and can avoid early deaths, reverse mild-to-moderate critical illness, avoid ICU admission, attenuate the severity of organ dysfunction, shorten ICU length of stay, and reduce short- and long-term mortality of critically ill patients. Future research is needed to identify effective models to implement emergency critical care systems in different healthcare systems.

Artificial intelligence in coronary artery calcium score: rationale, different approaches, and outcomes.

Almost 35 years after its introduction, coronary artery calcium score (CACS) not only survived technological advances but became one of the cornerstones of contemporary cardiovascular imaging. Its simplicity and quantitative nature established it as one of the most robust approaches for atherosclerotic cardiovascular disease risk stratification in primary prevention and a powerful tool to guide therapeutic choices. Groundbreaking advances in computational models and computer power translated into a surge of artificial intelligence (AI)-based approaches directly or indirectly linked to CACS analysis. This review aims to provide essential knowledge on the AI-based techniques currently applied to CACS, setting the stage for a holistic analysis of the use of these techniques in coronary artery calcium imaging. While the focus of the review will be detailing the evidence, strengths, and limitations of end-to-end CACS algorithms in electrocardiography-gated and non-gated scans, the current role of deep-learning image reconstructions, segmentation techniques, and combined applications such as simultaneous coronary artery calcium and pulmonary nodule segmentation, will also be discussed.

Clinical predictors of negative/equivocal SPECT imaging outcomes in primary hyperparathyroidism: Factors calling for 18F-choline-PET.

PURPOSE: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. METHODS: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. RESULTS: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. CONCLUSION: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.

Learning Curve of a Laparoscopic Pancreaticoduodenectomy Program at a Second Institution.

BACKGROUND: Historically, pancreaticoduodenectomy (PD) has been performed via a laparotomy, but increasingly, laparoscopic and robotic platforms are being employed for PD. Laparoscopic PD has a steep surgeon specific learning curve and programmatic elements that must be optimized. These factors may limit a surgeon who is proficient at laparoscopic PD to develop a program at another institution. We hypothesize that the learning curve for a surgeon transferring a program to a second institution is shorter than the initial laparoscopic PD learning curve for the same surgeon. METHODS: A retrospective review of patients who underwent laparoscopic PD for any indication at the first institution (FI) from 2012 to 2017 and the second institution (SI) from 2018 to 2021 was conducted. Standard statistical analysis was performed. The learning curve was identified using one-sided CUSUM analysis of operative times. RESULT: We identified 110 participants, 90 from the FI and 20 from the SI. More patients at the FI were diagnosed with periampullary adenocarcinoma on final pathology compared to the SI (65.6% vs 40.0%, P = .0132). FI operative times stabilized after the 25th laparoscopic PD and SI operative times stabilized after the 5th operation. No statistically significant difference was identified in postoperative complications. CONCLUSIONS: The learning curve and average operative time of an SI laparoscopic PD program was shorter than the initial learning curve for a single surgeon with comparable outcomes. This suggests that complex minimally invasive surgical programs can be safely transferred to another high-volume institution without significant loss of progress.

Cell-type-resolved mosaicism reveals clonal dynamics of the human forebrain.

Debate remains around the anatomical origins of specific brain cell subtypes and lineage relationships within the human forebrain1-7. Thus, direct observation in the mature human brain is critical for a complete understanding of its structural organization and cellular origins. Here we utilize brain mosaic variation within specific cell types as distinct indicators for clonal dynamics, denoted as cell-type-specific mosaic variant barcode analysis. From four hemispheres and two different human neurotypical donors, we identified 287 and 780 mosaic variants, respectively, that were used to deconvolve clonal dynamics. Clonal spread and allele fractions within the brain reveal that local hippocampal excitatory neurons are more lineage-restricted than resident neocortical excitatory neurons or resident basal ganglia GABAergic inhibitory neurons. Furthermore, simultaneous genome transcriptome analysis at both a cell-type-specific and a single-cell level suggests a dorsal neocortical origin for a subgroup of DLX1+ inhibitory neurons that disperse radially from an origin shared with excitatory neurons. Finally, the distribution of mosaic variants across 17 locations within one parietal lobe reveals that restriction of clonal spread in the anterior-posterior axis precedes restriction in the dorsal-ventral axis for both excitatory and inhibitory neurons. Thus, cell-type-resolved somatic mosaicism can uncover lineage relationships governing the development of the human forebrain.

18F-fluorodeoxyglucose uptake patterns in positron emission tomography/computed tomography caused by inflammation and/or infection after graft surgery for thoracic aortic dissection.

BACKGROUND: To identify 18F-fluorodeoxyglucose (FDG) uptake patterns in positron emission tomography/computed tomography (PET/CT) caused by infection, inflammation, surgical material, and/or graft coating. METHODS AND RESULTS: Of 610 consecutive patients with thoracic aortic graft surgery, 60 patients with 187 PET/CT were retrospectively included. We quantified FDG uptake in all grafts using maximum standardized uptake value (SUVmax) alone and in relation to liver background (SUVratio) and determined the uptake pattern. Mixed linear regression models with random slope and intercept were applied for the analysis of SUVratio over time and generalized estimating equations to analyze the associations with anastomosis uptake. FDG uptake was frequently focal (90%), higher in infected than in noninfected grafts (mean SUVratio 2.19; 95% CI 2.05-2.32 vs. 1.63; 1.46-1.79, P < 0.001), and decreasing slowly over time (SUVratio per year since surgery -0.048; 95% CI -0.15- 0.051, P = 0.34), without a difference in slope between infected and noninfected grafts (P = 0.52). There was no evidence of an interaction between SUVratio and use of BioGlue® surgical adhesive (intercept P = 0.73, slope P = 0.71), or graft coating (gelatin and collagen, all P > 0.7). FDG uptake at the anastomosis was more frequent in noninfected grafts than in infected grafts (66% vs. 21%, odds ratio (OR) 11.34; 95% CI 3.61-35.66, P < 0.001). This effect was attenuated by the use of BioGlue® (OR 5.05; 95% CI 0.45-56.9, P = 0.19). CONCLUSIONS: FDG uptake in PET/CT after thoracic aortic graft surgery is higher in infected grafts than in noninfected grafts. In noninfected grafts, focal uptake is also frequent, mostly anastomosis-associated, not associated with graft coating, and possibly affected by the use of BioGlue®.

Determination of ileal endogenous nitrogen losses and true ileal nitrogen digestibility during non-steady-state conditions of the 15N-isotope dilution technique.

The aim was to determine ileal endogenous nitrogen losses (ENL) and true ileal N-digestibility (TD-N) under non-steady-state conditions of the 15N-isotope dilution technique (15N-IDT), using diets generating low and high ENL and compare results to those obtained under steady-state conditions. Twelve growing pigs (mean LW 22.4 kg) fitted with a post-valve T-caecum cannula were fed an enzyme-hydrolysed casein (EHC)-based diet or an EHC diet + 4% quebracho tannins (QT) and were labelled via continuous 15N-leucine i.v. infusion or twice daily oral 15N-leucine administration. Digesta were collected daily over three consecutive hours with blood plasma sampled on the four consecutive days after cessation of 15N-labelling. There was a significant effect of sampling day on the dilution factor. Endogenous N losses were significantly lower for the EHC than the EHC+QT diet (2.41 vs. 8.69 g/kg DMI), while no significant effect of sampling day was observed. The TD-N of the EHC+QT diet did not differ from the TD-N of the EHC diet (95.1 vs. 92.0%). A significant effect of sampling day was observed for TD-N with day 1 and 2, being higher than day 4. Non-steady-state conditions overestimated ENL by 25-28% as compared to 3 h collections in steady-state conditions, but the relative overestimation was similar for the EHC diet as for the EHC+QT diet. TD-N did not differ significantly compared to 12 h steady-state measurements, but comparison to 3 h steady-state measurements showed that non-steady-state conditions overestimated TD-N for the EHC+QT diet by 9%. However, on day 4 this overestimation disappeared. Using the 15N-IDT during non-steady-state conditions can provide valuable additional data on endogenous N losses and TD-N.

The Monocle Sign on 18F-FDG PET Indicates Contralateral Peripheral Facial Nerve Palsy.

BACKGROUND: The aim of our study was to retrospectively analyze FDG PET/CT data in patients with facial nerve palsy (FNP) for the presence of the monocle sign. PATIENTS AND METHODS: A total of 85 patients with unilateral FNP were included into our study, thereof 73 with peripheral FNP and 12 with central FNP. FDG uptake (SUVmax, SUVmean, total lesion glycolysis) was measured in both orbicularis oculi muscles (OOMs). FDG uptake of paretic and nonparetic muscles was compared in patients with FNP (Wilcoxon test and Mann-Whitney U test) and was also compared with FDG uptake in 33 patients without FNP (Mann-Whitney U test). SUVmax ratios of OOM were compared. A receiver operating characteristic curve and Youden Index were used to determine the optimal cutoff SUVmax ratio for the prevalence of contralateral peripheral FNP. RESULTS: The SUVmax ratio of OOM was significantly higher in patients with peripheral FNP compared with patients with central FNP and those without FNP (1.70 ± 0.94 vs 1.16 ± 0.09 vs 1.18 ± 0.21, respectively; P < 0.001). The SUVmax ratio of OOM yielded an area under the curve (AUC) of 0.719 (95% confidence interval, 0.630-0.809), with an optimal cutoff of 1.41, yielding a specificity of 94.4% and a sensitivity of 44.1% for identifying contralateral peripheral FNP. One hundred percent specificity is achieved using a cutoff of 1.91 (sensitivity, 29.4%). CONCLUSIONS: Asymmetrically increased FDG uptake of the OOM (the "monocle sign") indicates contralateral peripheral FNP. A nearly 2-fold higher SUVmax represents a practically useful cutoff.

Asian elephant calf physiology and mahout perspectives during taming in Myanmar.

A quarter of Asian elephants are captive, with greater than 90% of these tamed and cared for by handlers (mahouts) in Asia. Although taming is a much-discussed welfare issue, no studies to our knowledge have empirically assessed its impact on calves, and dialogue surrounding taming often lacks perspectives of those involved. Here, we interviewed mahouts involved in taming and monitored five physiological measures (faecal glucocorticoid metabolites (FGMs), serum cortisol, glucose, creatine kinase (CK) and heterophil:lymphocyte (H:L)) over the first 10 days of taming and following six months in 41 calves undergoing taming and 16 control individuals. These measures assess the duration and intensity of stress during taming. Interviews suggested mahouts had major concerns for their safety when discussing changing taming practices, an important consideration for future management. Calf physiological measures were elevated by 50-70% (FGMs/cortisol/glucose), 135% (H:L) and greater than 500% (CK) over the first few days of taming, indicative of elevated stress, not seen to the same extent in control adults. Some measures stabilized sooner (glucose/cortisol/CK/FGM: 7-10 days) than others (H:L: one-two months), indicating mostly acute stress. Our findings inform the welfare of approximately 15 000 captive elephants around the world. Future studies should compare taming in different populations and consider calf and mahout welfare.

Evaluating the biodistribution for [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET/CT with an inter- and intrapatient based analysis.

BACKGROUND: Liver uptake in [68Ga]Ga-PSMA-11 PET is used as an internal reference in addition to clinical parameters to select patients for [177Lu]Lu-PSMA-617 radioligand therapy (RLT). Due to increased demand, [68Ga]Ga-PSMA-11 was replaced by [18F]F-PSMA-1007, a more lipophilic tracer with different biodistribution and splenic uptake was suggested as a new internal reference. We compared the intra-patient tracer distribution between [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007. METHODS: Fifty patients who underwent PET examinations in two centers with both [18F]F-PSMA-1007 and [68Ga]Ga-PSMA-11 within one year were included. Mean standardized uptake values (SUVmean) were obtained for liver, spleen, salivary glands, blood pool, and bone. Primary tumor, local recurrence, lymph node, bone or visceral metastasis were also assessed for intra- and inter-individual comparison. RESULTS: Liver SUVmean was significantly higher with [18F]F-PSMA-1007 (11.7 ± 3.9) compared to [68Ga]Ga-PSMA-11 (5.4 ± 1.7, p < .05) as well as splenic SUVmean (11.2 ± 3.5 vs.8.1 ± 3.5, p < .05). The blood pool was comparable between the two scans. Malignant lesions did not show higher SUVmean on [18F]F-PSMA-1007. Intra-individual comparison of liver uptake between the two scans showed a linear association for liver uptake with SUVmean [68Ga]Ga-PSMA-11 = 0.33 x SUVmean [18F]F-PSMA-1007 + 1.52 (r = .78, p < .001). CONCLUSION: Comparing biodistribution of [68Ga]Ga and [18F]F tracers, liver uptake on [68Ga]Ga-PSMA-11 PET is the most robust internal reference value. Liver uptake of [18F]F-PSMA-1007 was significantly higher, but so was the splenic uptake. The strong intra-individual association of hepatic accumulation between the two scans may allow using of a conversion factor for [18F]F-PSMA-1007 as a basis for RLT selection.

Lifelong persistence of nuclear RNAs in the mouse brain.

Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type-specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin.

Clinical and paraclinical characteristics of optic neuritis in the context of the McDonald criteria 2017.

Optic neuritis is often an initial symptom in multiple sclerosis (MS) or clinically isolated syndrome (CIS), yet comprehensive studies using the 2017 McDonald criteria for MS are scarce. Patient records from our academic centre (2010-2018) were reviewed. Using the 2017 McDonald criteria, three groups were formed: MS optic neuritis (optic neuritis with confirmed MS), CIS optic neuritis (optic neuritis without confirmed MS) and suspected optic neuritis (sON). We compared clinical and paraclinical findings among the groups to identify predictors for CIS- or MS-optic neuritis. The study included 129 MS, 108 CIS, and 44 sON cases. The combination of visual impairment, dyschromatopsia, and retrobulbar pain was observed in 47% of MS patients, 42% of CIS patients, and 30% of sON patients. Dyschromatopsia was the strongest indicator of MS or CIS diagnosis in the backward regression model. 56% of MS patients had relative afferent pupillary defect, 61% optic nerve anomalies within magnetic resonance imaging, and 81% abnormal visual evoked potentials. Our results emphasize the challenges in diagnosing optic neuritis, as not all patients with objectively diagnosed MS exhibit the triad of typical symptoms. To address potentially missing clinical features, incorporating additional paraclinical findings is proposed.

Survival in Patients With De Novo Metastatic Prostate Cancer.

This cross-sectional study investigates trends in overall survival among patients with newly diagnosed metastatic prostate cancer in 2 national registries in the United States.

The WHO atlas for female-genital schistosomiasis: Co-design of a practicable diagnostic guide, digital support and training.

Up to 56 million young and adult women of African origin suffer from Female Genital Schistosomiasis (FGS). The transmission of schistosomiasis happens through contact with schistosomiasis infested fresh water in rivers and lakes. The transmission vector is the snail that releases immature worms capable of penetrating the human skin. The worm then matures and mates in the blood vessels and deposits its eggs in tissues, causing urogenital disease. There is currently no gold standard for FGS diagnosis. Reliable diagnostics are challenging due to the lack of appropriate instruments and clinical skills. The World Health Organisation (WHO) recommends "screen-and-treat" cervical cancer management, by means of visual inspection of characteristic lesions on the cervix and point-of-care treatment as per the findings. FGS may be mistaken for cervical cancer or sexually transmitted diseases. Misdiagnosis may lead to the wrong treatment, increased risk of exposure to other infectious diseases (human immunodeficiency virus and human papilloma virus), infertility and stigmatisation. The necessary clinical knowledge is only available to a few experts in the world. For an appropriate diagnosis, this knowledge needs to be transferred to health professionals who have minimal or non-existing laboratory support. Co-design workshops were held with stakeholders (WHO representative, national health authority, FGS experts and researchers, gynaecologists, nurses, medical doctors, public health experts, technical experts, and members of the public) to make prototypes for the WHO Pocket Atlas for FGS, a mobile diagnostic support tool and an e-learning tool for health professionals. The dissemination targeted health facilities, including remote areas across the 51 anglophone, francophone and lusophone African countries. Outcomes were endorsed by the WHO and comprise a practical diagnostic guide for FGS in low-resource environments.

The dynamic buffering of social support on depressive symptoms and cancer worries in patients seeking cancer genetic counseling.

PURPOSE: Social support is a crucial protective factor against psychological concerns in patients with cancer. However, there is limited knowledge regarding the differential impacts of social support on cancer worries and depressive symptoms in patients undergoing genetic counseling for hereditary cancer. The current study utilized a high-volume database from a multi-site cancer genetics clinic to assess the impact of perceived social support on depressive symptoms and cancer worries among patients of different age groups (young versus older patients) and diagnosis status (diagnosed survivors versus undiagnosed). METHODS: 6,666 patients completed brief assessments of depressive symptoms, cancer worries, social support, and demographic questionnaires as part of routine clinical care between October 2016 and October 2020. Logistics and moderated regression were used to analyze the relationships between social support, depressive symptoms, and cancer worries. RESULTS: Increased social support was associated with fewer depressive symptoms and fewer cancer worries across all patients. Social support mitigated depressive symptoms most significantly for young adult patients with and without cancer. Social support mitigated cancer worries most significantly for young adults with cancer and older adults without cancer. CONCLUSIONS: While results were mixed, general findings upheld original hypotheses. Social support buffered depressive symptoms and cancer worries differentially for patients of different ages and different disease status. IMPLICATIONS FOR CANCER SURVIVORS: Social support groups are beneficial for all patients and should be emphasized by cancer clinics. However, increasing patient-tailored and age-appropriate support networks will be crucial for managing depression and cancer worries for high-risk survivors: young adults with cancer.

Organic carbon accumulation in British saltmarshes.

Saltmarshes are a crucial component of the coastal carbon (C) system and provide a natural climate regulation service through the accumulation and long-term storage of organic carbon (OC) in their soils. These coastal ecosystems are under growing pressure from a changing climate and increasing anthropogenic disturbance. To manage and protect these ecosystems for C and to allow their inclusion in emissions and natural-capital accounting, as well as carbon markets, accurate and reliable estimates of OC accumulation are required. However, globally, such data are rare or of varying quality. Here, we quantify sedimentation rates and OC densities for 21 saltmarshes in Great Britain (GB). We estimate that, on average, saltmarshes accumulate OC at a rate of 110.88 ± 43.12 g C m-2 yr-1. This is considerably less than widely applied global saltmarsh averages. It is therefore highly likely that the contribution of northern European saltmarshes to global saltmarsh OC accumulation has been significantly overestimated. Taking account of the climatic, geomorphological, oceanographic, and ecological characteristics of all GB saltmarshes and the areal extent of different saltmarsh zones, we estimate that the 451.65 km2 of GB saltmarsh accumulates 46,563 ± 4353 t of OC annually. These low OC accumulation rates underline the importance of the 5.20 ± 0.65 million tonnes of OC already stored in these vulnerable coastal ecosystems. Going forward the protection and preservation of the existing stores of OC in GB saltmarshes must be a priority for the UK as this will provide climate benefits through avoided emissions several times more significant than the annual accumulation of OC in these ecosystems.