Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score.

OBJECTIVE: To develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist. METHODS: The cutoffs definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability. RESULTS: The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/flare or were satisfied or not satisfied with current illness outcome. CONCLUSION: The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts, and are therefore suitable for use in clinical trials and routine practice.

The Eye as the Window to the Heart: Optical Coherence Tomography Angiography Biomarkers as Indicators of Cardiovascular Disease.

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism. Optical coherence tomography angiography (OCTA) studies have specifically identified reduced capillary densities at the level of the retina in several eye diseases including glaucoma. This narrative review examines the published data related to OCTA-assessed microvasculature biomarkers and major systemic cardiovascular disease. While loss of capillaries is being established in various ocular disease, pilot data suggest that changes in the retinal microvasculature, especially within the macula, may also reflect small vessel damage occurring in other organs resulting from cardiovascular disease. Current evidence suggests retinal microvascular biomarkers as potential indicators of major systemic cardiovascular diseases, including systemic arterial hypertension, atherosclerotic disease, and congestive heart failure.

Cardiovascular sex-differences: insights via physiology-based modeling and potential for noninvasive sensing via ballistocardiography.

In this study, anatomical and functional differences between men and women in their cardiovascular systems and how these differences manifest in blood circulation are theoretically and experimentally investigated. A validated mathematical model of the cardiovascular system is used as a virtual laboratory to simulate and compare multiple scenarios where parameters associated with sex differences are varied. Cardiovascular model parameters related with women's faster heart rate, stronger ventricular contractility, and smaller blood vessels are used as inputs to quantify the impact (i) on the distribution of blood volume through the cardiovascular system, (ii) on the cardiovascular indexes describing the coupling between ventricles and arteries, and (iii) on the ballistocardiogram (BCG) signal. The model-predicted outputs are found to be consistent with published clinical data. Model simulations suggest that the balance between the contractile function of the left ventricle and the load opposed by the arterial circulation attains similar levels in females and males, but is achieved through different combinations of factors. Additionally, we examine the potential of using the BCG waveform, which is directly related to cardiovascular volumes, as a noninvasive method for monitoring cardiovascular function. Our findings provide valuable insights into the underlying mechanisms of cardiovascular sex differences and may help facilitate the development of effective noninvasive cardiovascular monitoring methods for early diagnosis and prevention of cardiovascular disease in both women and men.

Potential for biosimilars in rheumatology in Africa.

Biosimilars are products which are highly similar to a reference biologic product (RBP). In Africa, regulatory frameworks for biosimilar approval are still in development in many countries and few biosimilars for rheumatic diseases are currently available. The use of biosimilar medicines in Africa provides an important opportunity to treat more rheumatology patients with biologic drugs. This editorial aims to shed a light on the potential benefits, challenges and current efforts, regarding the use of biosimilars in Africa in Rheumatology.

Development of outcome measures for giant cell arteritis for use in clinical trials and standard practice.

BACKGROUND: Developments in outcome measures in the rheumatic diseases are promoted by the development of successful treatments. Giant cell arteritis (GCA) is a multifaceted disorder and, therefore, measurement of multiple outcomes is relevant to this illness. It is a privilege to analyze and monitor/transfer long-term patients' management outcomes particularly if the same outcomes are used in practice and in trials. OBJECTIVE: To classify the outcome measures for GCA with a discriminative ability to identify the disease activity status and response to therapy. METHODS: This study was composed of two steps, instrument design (item generation) and judgmental evidence. A panel of 13 experts was used to validate the instrument through quantitative (content validity) and qualitative (cognitive interviewing) methods. Content validity index was used to assess content validity quantitatively. RESULTS: Five items achieved high content validity where item-content validity index score was >0.79, and in the meantime achieved high content validity response score reflecting greater agreement among panel members. Through qualitative methods, items were improved until saturation was achieved. This agreed with the expert panel ranking of the items included in GCA disease outcome measures set. CONCLUSION: For daily clinical practice, outcome measures should reflect the patients' disease activity status and have to be easily assessed and recorded. The study identified composite outcome measures for GCA able to assess the disease state and monitor response to therapy. Key Points • Despite the cohort studies published in giant cell arteritis (GCA), there are no fully validated outcome measures for use in standard practice or clinical trials. • There is a gap in international standards for assessing GCA disease activity. • Identifying disease specific outcome measures is vital for monitoring response to therapy, treatment case series and therapeutic clinical trials in GCA. • This study was carried out aiming to classify the outcome measures for GCA with a discriminative ability to identify the disease activity status and response to therapy.

Osteoporosis treatment gap in patients at risk of fracture in Egypt: a multi-center, cross-sectional observational study.

Despite the wide availability of a wide variety of approved osteoporosis medications and DXA scan centers in Egypt, only a minority of patients at high risk of sustaining a fragility fracture receive treatment, even after their first fracture. Such big "treatment gap" leaves the most high-risk individuals unprotected against fragility fractures. This study provides a benchmark to monitor national trends in osteoporosis management and service uptake. PURPOSE: To assess the treatment gap among men and postmenopausal women presenting with a fragility fracture, and to analyze the characteristics and fracture risks of the patients presenting with an index fragility fracture. METHODS: This was a multi-center, cross-sectional, observational study. Both men and postmenopausal women, admitted with an osteoporotic fracture (whether major osteoporosis or hip fracture), were consecutively recruited for this work. The fracture risk was assessed based on their FRAX calculation prior to the index fracture. All the patients were assessed for their falls and sarcopenia risks. Blood tests for bone profile as well as DXA scan were offered to all the patients. RESULTS: Two hundred and thirty-six patients presenting with fragility fractures were included in this work. 70.8% were women and 29.2% were men. Mean age was 70.1 (SD = 9.2) years. Ten-year probability of fracture (without BMD) was high in 65.9% of the postmenopausal women and 40.3% of the men. 82.1% of the postmenopausal women and 100% in men identified to be eligible for osteoporosis therapy did not receive any form of osteoporosis therapy. FRAX score correlated significantly with bone mineral density assessment at both hip and spine. Falls, sarcopenia, and functional disability showed significant relation to the fracture risk. CONCLUSIONS: There is a large treatment gap in Egyptian older adults. The recent guidelines for osteoporosis management in Egypt endorsed fracture centric approach to identify people at risk. The gap appears to be related to a low rate of osteoporosis diagnosis and lack of patient education.

Implementing a transformative approach to the coral reefs' recovery phase.

Mitigation and rehabilitation are responses to climate change and human misuse. However, many regions worldwide still lose coral reefs even after implementing these responses. We chose Hurghada city, on the Red Sea, and Weizhou island, on the South China Sea, as sample regions to assess their various modes of coral community structure loss against the combined climatic and human impact drivers that led to this shift. Despite the former being considered a regional coral refuge, while the latter was limited, both regions have previously intervened with coral restoration. We found that even after three decades of impact cessation by forcing laws, most coral reef states are still declining (about a third and a half in both cities), have not harnessed the existing crowded larval density, and are unrecovered. Such findings imply that the combined impacts will persist, necessitating a broad connectivity analysis that enables a suitable intervention (hybrid solutions hypothesis). Each state of coral categories was connected to certain combined stressor factors using our broad connectivity analysis to grasp the extent and relative contribution of coral community shift since our data obtained from comparable sites were widely varied. Moreover, destructive emerged changes have transformed the coral community structure under the forced adaptation scenario of the community structure, boosting those who can resist at the expense of others. To prove our hypothesis, we used the connectivity findings in determining the optimal technique and spots for coral rehabilitation around the two cities. We then compared our findings with the outcomes of two other existing adjacent restoration projects related to other endeavors. Our hybrid approach harvested coral larvae that had been wasted in both cities. Thus, hybrid solutions are globally required for such cases, and proper early interventions are needed to maintain the genotype power to boost coral adaptability throw global ecological settings.

Minipercutaneous Nephrolithotomy in the Management of Large and Complex Renal Calculi in Children: How Effective Is It?

Purpose: To evaluate the efficacy and safety of minipercutaneous nephrolithotomy (PCNL) in the management of large and complex calculi in children. Patients and Methods: From May 2017 to April 2021, a total of 41 pediatric cases were diagnosed with large/complex renal stones (partial-total staghorn) and following a detailed biochemical evaluation and thorough radiological examination (plain abdominal radiograph, urinary ultrasound, noncontrast and/or computed tomography), all cases underwent mini-PCNL procedure for the minimal invasive management of these calculi. Preoperative, intraoperative, and postoperative data were analyzed and reported in detail. Results: A total of 41 procedures were performed in 26 boys and 15 girls (male/female = 1.73). While the age of the kids ranged from 2.5 to 10 years (mean 6.74 ± 2.76), mean size of the stones was 16.28 ± 3.43 mm (range 11-24) with a mean stone density value of 816 HU (range 550-1350). Evaluation of the success rates in terms of complete stone clearance on postoperative day 1 revealed that while 73.2% (30/41), residual fragments have been noted in 11 cases (26.8%). Size of the residual fragments ranged from 2 to 7 mm (mean 4.3). Of those children, 10 cases required flexible ureteroscopy for stone removal, and in 1 case, placement of Double-J was adequate for spontaneous passage. During a 3-month follow-up, the stone-free rate (SFR) increased to 100% without any residual fragment left. Conclusions: Mini-PCNL with holmium laser lithotripsy is an effective and safe treatment alternative in the minimal invasive management of large/complex kidney stones in children with high SFRs.

Leveraging deep learning-based segmentation and contours-driven deformable registration for dose accumulation in abdominal structures.

Purpose: Discrepancies between planned and delivered dose to GI structures during radiation therapy (RT) of liver cancer may hamper the prediction of treatment outcomes. The purpose of this study is to develop a streamlined workflow for dose accumulation in a treatment planning system (TPS) during liver image-guided RT and to assess its accuracy when using different deformable image registration (DIR) algorithms. Materials and Methods: Fifty-six patients with primary and metastatic liver cancer treated with external beam radiotherapy guided by daily CT-on-rails (CTOR) were retrospectively analyzed. The liver, stomach and duodenum contours were auto-segmented on all planning CTs and daily CTORs using deep-learning methods. Dose accumulation was performed for each patient using scripting functionalities of the TPS and considering three available DIR algorithms based on: (i) image intensities only; (ii) intensities + contours; (iii) a biomechanical model (contours only). Planned and accumulated doses were converted to equivalent dose in 2Gy (EQD2) and normal tissue complication probabilities (NTCP) were calculated for the stomach and duodenum. Dosimetric indexes for the normal liver, GTV, stomach and duodenum and the NTCP values were exported from the TPS for analysis of the discrepancies between planned and the different accumulated doses. Results: Deep learning segmentation of the stomach and duodenum enabled considerable acceleration of the dose accumulation process for the 56 patients. Differences between accumulated and planned doses were analyzed considering the 3 DIR methods. For the normal liver, stomach and duodenum, the distribution of the 56 differences in maximum doses (D2%) presented a significantly higher variance when a contour-driven DIR method was used instead of the intensity only-based method. Comparing the two contour-driven DIR methods, differences in accumulated minimum doses (D98%) in the GTV were >2Gy for 15 (27%) of the patients. Considering accumulated dose instead of planned dose in standard NTCP models of the duodenum demonstrated a high sensitivity of the duodenum toxicity risk to these dose discrepancies, whereas smaller variations were observed for the stomach. Conclusion: This study demonstrated a successful implementation of an automatic workflow for dose accumulation during liver cancer RT in a commercial TPS. The use of contour-driven DIR methods led to larger discrepancies between planned and accumulated doses in comparison to using an intensity only based DIR method, suggesting a better capability of these approaches in estimating complex deformations of the GI organs.

Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase 1 Trial and Imaging-based Biomarker Validation.

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response. METHODS AND MATERIALS: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m2) with concurrent capecitabine and RT in cohort sizes of 3 starting at the lowest dose. Dose limiting toxicity was defined as grade 3 or higher toxicity. Patients were restaged 4 to 6 weeks post-CRT completion, and surgical resection was offered to those with stable/responsive disease. We scored the tumor interface response (IR) postchemotherapy and post-CRT into type I (remained/became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. P ≤ .05 was considered significant. RESULTS: Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. Level 2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (P = .004) and PFS (P = .03) compared with type II IR. CONCLUSIONS: We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.

Mass Transport Model of Radiation Response: Calibration and Application to Chemoradiation for Pancreatic Cancer.

PURPOSE: The benefit of radiation therapy for pancreatic ductal adenocarcinoma (PDAC) remains unclear. We hypothesized that a new mechanistic mathematical model of chemotherapy and radiation response could predict clinical outcomes a priori, using a previously described baseline measurement of perfusion from computed tomography scans, normalized area under the enhancement curve (nAUC). METHODS AND MATERIALS: We simplified an existing mass transport model that predicted cancer cell death by replacing previously unknown variables with averaged direct measurements from randomly selected pathologic sections of untreated PDAC. This allowed using nAUC as the sole model input to approximate tumor perfusion. We then compared the predicted cancer cell death to the actual cell death measured from corresponding resected tumors treated with neoadjuvant chemoradiation in a calibration cohort (n = 80) and prospective cohort (n = 25). After calibration, we applied the model to 2 separate cohorts for pathologic and clinical associations: targeted therapy cohort (n = 101), cetuximab/bevacizumab + radiosensitizing chemotherapy, and standard chemoradiation cohort (n = 81), radiosensitizing chemotherapy to 50.4 Gy in 28 fractions. RESULTS: We established the relationship between pretreatment computed v nAUC to pathologically verified blood volume fraction of the tumor (r = 0.65; P = .009) and fractional tumor cell death (r = 0.97-0.99; P < .0001) in the calibration and prospective cohorts. On multivariate analyses, accounting for traditional covariates, nAUC independently associated with overall survival in all cohorts (mean hazard ratios, 0.14-0.31). Receiver operator characteristic analyses revealed discrimination of good and bad prognostic groups in the cohorts with area under the curve values of 0.64 to 0.71. CONCLUSIONS: This work presents a new mathematical modeling approach to predict clinical response from chemotherapy and radiation for PDAC. Our findings indicate that oxygen/drug diffusion strongly influences clinical responses and that nAUC is a potential tool to select patients with PDAC for radiation therapy.

Mechanism-Driven Modeling to Aid Non-invasive Monitoring of Cardiac Function via Ballistocardiography.

Left ventricular (LV) catheterization provides LV pressure-volume (P-V) loops and it represents the gold standard for cardiac function monitoring. This technique, however, is invasive and this limits its applicability in clinical and in-home settings. Ballistocardiography (BCG) is a good candidate for non-invasive cardiac monitoring, as it is based on capturing non-invasively the body motion that results from the blood flowing through the cardiovascular system. This work aims at building a mechanistic connection between changes in the BCG signal, changes in the P-V loops and changes in cardiac function. A mechanism-driven model based on cardiovascular physiology has been used as a virtual laboratory to predict how changes in cardiac function will manifest in the BCG waveform. Specifically, model simulations indicate that a decline in LV contractility results in an increase of the relative timing between the ECG and BCG signal and a decrease in BCG amplitude. The predicted changes have subsequently been observed in measurements on three swine serving as pre-clinical models for pre- and post-myocardial infarction conditions. The reproducibility of BCG measurements has been assessed on repeated, consecutive sessions of data acquisitions on three additional swine. Overall, this study provides experimental evidence supporting the utilization of mechanism-driven mathematical modeling as a guide to interpret changes in the BCG signal on the basis of cardiovascular physiology, thereby advancing the BCG technique as an effective method for non-invasive monitoring of cardiac function.

Histopathological and biochemical aspects of grafted and non-grafted cucumber infected with stem rot caused by Fusarium spp.

Cucumber grafting has been used in Egypt recently to induce soil diseases tolerance. The impact of various grafting techniques on the vulnerability of grafted cucumber seedlings to Fusarium which stimulates the stem rot was investigated. Consequently, the anatomical and physiological studies were carried out on the diseased and healthy grafted cucumber seedlings, comparing with the non-grafted ones. Fusarium equiseti (MW216971.1) caused a severe stem rot of the grafted seedling through affecting the connection area of the different grafting methods, leading to complete seedling death. The hole insertion grafting method significantly exhibited the highest diseases incidence (100%), and mean disease severity index (5) when inoculated with F. equiseti. The pathogen remarkably affected the graft union area causing tissue discoloration and decay. The levels of antioxidant enzymes and total phenols were significantly enhanced in the diseased grafted and self-rooted cucumber. However, the diseased grafted cucumber recorded significantly the highest values of the antioxidant enzymes activities and total phenolic content when compared with the self-rooted ones. The results of SDS-PAGE profile revealed variations in the leaves protein profile of the grafted and self- rooted seedlings in response to Fusarium infection. Taken together, grafting cucumber onto a resistant rootstock using the splice technique can alleviate the stem rot severity caused by Fusarium spp. by enhancing the histological, physiological and molecular defense response of the grafted seedling.

Loss of Rnf43 Accelerates Kras-Mediated Neoplasia and Remodels the Tumor Immune Microenvironment in Pancreatic Adenocarcinoma.

BACKGROUND & AIMS: RNF43 is an E3 ubiquitin ligase that is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC) and precursor cystic neoplasms of the pancreas. The impact of RNF43 mutations on PDAC is poorly understood and autochthonous models have not been characterized sufficiently. In this study, we describe a genetically engineered mouse model (GEMM) of PDAC with conditional expression of oncogenic Kras and deletion of the catalytic domain of Rnf43 in exocrine cells. METHODS: We generated Ptf1a-Cre;LSL-KrasG12D;Rnf43flox/flox (KRC) and Ptf1a-Cre; LSL-KrasG12D (KC) mice and animal survival was assessed. KRC mice were sacrificed at 2 months, 4 months, and at moribund status followed by analysis of pancreata by single-cell RNA sequencing. Comparative analyses between moribund KRC and a moribund Kras/Tp53-driven PDAC GEMM (KPC) was performed. Cell lines were isolated from KRC and KC tumors and interrogated by cytokine array analyses, ATAC sequencing, and in vitro drug assays. KRC GEMMs were also treated with an anti-CTLA4 neutralizing antibody with treatment response measured by magnetic response imaging. RESULTS: We demonstrate that KRC mice display a marked increase in incidence of high-grade cystic lesions of the pancreas and PDAC compared with KC. Importantly, KRC mice have a significantly decreased survival compared with KC mice. Using single-cell RNA sequencing, we demonstrated that KRC tumor progression is accompanied by a decrease in macrophages, as well as an increase in T and B lymphocytes, with evidence of increased immune checkpoint molecule expression and affinity maturation, respectively. This was in stark contrast to the tumor immune microenvironment observed in the KPC PDAC GEMM. Furthermore, expression of the chemokine CXCL5 was found to be specifically decreased in KRC cancer cells by means of epigenetic regulation and emerged as a putative candidate for mediating the unique KRC immune landscape. CONCLUSIONS: The KRC GEMM establishes RNF43 as a bona fide tumor suppressor gene in PDAC. This GEMM features a markedly different immune microenvironment compared with previously reported PDAC GEMMs and puts forth a rationale for an immunotherapy approach in this subset of PDAC cases.

Silver nanoparticles as a viricidal agent to inhibit plant-infecting viruses and disrupt their acquisition and transmission by their aphid vector.

Silver nanoparticles (AgNPs) are a potentially effective tool for preventing viral plant diseases. This study was carried out to evaluate the effectiveness of AgNPs for managing bean yellow mosaic virus (BYMV) disease in faba bean plants from the plant-virus-vector interaction side. AgNPs were evaluated as foliar protective and curative agents. In addition, the effect of AgNPs on virus acquisition and transmission by its vector aphid was investigated. The results indicated that AgNPs exhibited curative viricidal activity and were able to inactivate BYMV when applied 48 hours after virus inoculation. The occurrence of disease was prevented using an AgNP concentration as low as 100 mg L-1, whereas virus infection was completely inhibited when plants were preventatively treated with AgNPs at a concentration of to 200 mg L-1 24 h before virus inoculation. AgNPs proved to be highly bio-reactive, binding to viral particles and suppressing their replication and accumulation within plant tissues. Moreover, AgNPs, at all concentrations tested, were found to upregulate the pathogenesis-related gene PR-1 and induce the production of defense-related oxidizing enzymes in treated plants. Exposure of aphids to AgNPs-treated plants before virus acquisition reduced BYMV acquisition and transmission efficiency by 40.65 to 100% at 24 h post-application, depending on the AgNP dosage. At 10 days after treatment, virus acquisition was reduced by 36.82% and 79.64% upon exposure to AgNPs at a concentration of 250 and 300 mg L-1, respectively. These results suggest that AgNPs have curative viricidal activity due to targeting the virus coat protein and affecting virus-vector interactions. Accordingly, AgNPs may contribute to alleviating the natural disease and virus transmission under field conditions. This is the first report on the activity of nanomaterials against plant virus acquisition and transmission by insects.

Noninvasive cardiovascular monitoring based on electrocardiography and ballistocardiography: a feasibility study on patients in the surgical intensive care unit.

The time interval between the peaks in the electroccardiogram (ECG) and ballistocardiogram (BCG) waveforms, TEB, has been associated with the pre-ejection period (PEP), which is an important marker of ventricular contractility. However, the applicability of BCG-related markers in clinical practice is limited by the difficulty to obtain a replicable and consistent signal on patients. In this study, we test the feasibility of BCG measurements within a complex clinical setting, by means of an accelerometer under the head pillow of patients admitted to the Surgical Intensive Care Unit (SICU). The proposed technique proved capable of capturing TEB based on the R peaks in the ECG and the BCG in its head-to-toe and dorso- ventral directions. TEB detection was found to be consistent and repeatable both in healthy individuals and SICU patients over multiple data acquisition sessions. This work provides a promising starting point to investigate how TEB changes may relate to the patients' complex health conditions and give additional clinical insight into their care needs.

Benchmarking Outcomes after Ablative Radiotherapy for Molecularly Characterized Intrahepatic Cholangiocarcinoma.

We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED10) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2-18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED10 was 98 Gy (range: 81-144 Gy). The median (95% confidence interval) follow-up was 58 (42-104) months from diagnosis and 39 (33-74) months from RT. The median OS was 32 (29-35) months after diagnosis and 20 (16-24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65-80%), 81% (73-87%), and 34% (26-42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted.

Laparoscopic One Anastomosis Gastric Bypass Versus Laparoscopic Roux-en-Y Gastric Bypass Effects on Pre-existing Mild-to-Moderate Gastroesophageal Reflux Disease in Patients with Obesity: a Randomized Controlled Study.

BACKGROUND: Patients with obesity having GERD usually undergo Roux-en-Y gastric bypass (RYGB) as the procedure of choice. However, the emergence of one anastomosis gastric bypass (OAGB) as a less time-consuming operation with fewer complications offers a potential option for these patients. STUDY DESIGN: This randomized controlled trial included 80 patients (out of 457 screened) with mild-to-moderate GERD that were equally divided into two groups for OAGB and RYGB. GERD was diagnosed by 20-item questionnaire, upper endoscopy, 24-h pH monitoring, and manometry. Follow-up at 6 and 12 months was done. RESULTS: No significant differences were found between the two groups regarding demographic data, comorbidities, and weight loss. OAGB had less operative time and fewer complications. Both procedures had comparable favorable effects in reducing the GERD symptoms evidenced by upper endoscopy, 24-h pH monitoring, and manometry. CONCLUSION: OAGB is a promising bariatric procedure in weight loss for patients with obesity having mild-to-moderate GERD (up to grade B esophagitis by Los Angeles score). Furthermore, wide-scale studies and on more severe degrees of GERD are required to fully understand its benefits in GERD patients with obesity.

Combining Physiology-Based Modeling and Evolutionary Algorithms for Personalized, Noninvasive Cardiovascular Assessment Based on Electrocardiography and Ballistocardiography.

Purpose: This study proposes a novel approach to obtain personalized estimates of cardiovascular parameters by combining (i) electrocardiography and ballistocardiography for noninvasive cardiovascular monitoring, (ii) a physiology-based mathematical model for predicting personalized cardiovascular variables, and (iii) an evolutionary algorithm (EA) for searching optimal model parameters. Methods: Electrocardiogram (ECG), ballistocardiogram (BCG), and a total of six blood pressure measurements are recorded on three healthy subjects. The R peaks in the ECG are used to segment the BCG signal into single BCG curves for each heart beat. The time distance between R peaks is used as an input for a validated physiology-based mathematical model that predicts distributions of pressures and volumes in the cardiovascular system, along with the associated BCG curve. An EA is designed to search the generation of parameter values of the cardiovascular model that optimizes the match between model-predicted and experimentally-measured BCG curves. The physiological relevance of the optimal EA solution is evaluated a posteriori by comparing the model-predicted blood pressure with a cuff placed on the arm of the subjects to measure the blood pressure. Results: The proposed approach successfully captures amplitudes and timings of the most prominent peak and valley in the BCG curve, also known as the J peak and K valley. The values of cardiovascular parameters pertaining to ventricular function can be estimated by the EA in a consistent manner when the search is performed over five different BCG curves corresponding to five different heart-beats of the same subject. Notably, the blood pressure predicted by the physiology-based model with the personalized parameter values provided by the EA search exhibits a very good agreement with the cuff-based blood pressure measurement. Conclusion: The combination of EA with physiology-based modeling proved capable of providing personalized estimates of cardiovascular parameters and physiological variables of great interest, such as blood pressure. This novel approach opens the possibility for developing quantitative devices for noninvasive cardiovascular monitoring based on BCG sensing.