Portal hypertension-like pattern in coronavirus disease 2019 acute respiratory distress syndrome.

OBJECTIVES: Although respiratory failure is the most common feature in coronavirus disease 2019 (COVID-19), abdominal organ involvement is likewise frequently observed. To investigate visceral and thoracic circulation and abdominal organ damage in COVID-19 patients. MATERIALS AND METHODS: A monocentric observational study was carried on. In COVID-19 patients affected by acute respiratory distress syndrome (ARDS) (n = 31) or mild pneumonia (n = 60) thoracoabdominal circulation was evaluated using Doppler-ultrasound and computed tomography. The study also included non-COVID-19 patients affected by ARDS (n = 10) or portal hypertension (n = 10) for comparison of the main circulatory changes. RESULTS: Patients affected by COVID-19 ARDS showed hyperdynamic visceral flow and increased portal velocity, hepatic artery resistance-index, and spleen diameter relative to those with mild-pneumonia (p = 0.001). Splanchnic circulatory parameters significantly correlated with the main respiratory indexes (p < 0.001) and pulmonary artery diameter (p = 0.02). The chest and abdominal vascular remodeling pattern of COVID-19 ARDS patients resembled the picture observed in the PH group, while differed from that of the non-COVID ARDS group. A more severe COVID-19 presentation was associated with worse liver dysfunction and enhanced inflammatory activation; these parameters both correlated with abdominal (p = 0.04) and chest imaging measures (p = 0.03). CONCLUSION: In COVID-19 ARDS patients there are abdominal and lung vascular modifications that depict a portal hypertension-like pattern. The correlation between visceral vascular remodeling, pulmonary artery enlargement, and organ damage in these critically ill patients is consistent with a portal hyperlfow-like syndrome that could contribute to the peculiar characteristics of respiratory failure in these patients. CLINICAL RELEVANCE STATEMENT: our data suggest that the severity of COVID-19 lung involvement is directly related to the development of a portal hyperflow-like syndrome. These observations should help in defining the need for a closer monitoring, but also to develop dedicated therapeutic strategies.

Limb salvage and survival after urgent surgical treatment of popliteal artery aneurysm.

BACKGROUND: Popliteal artery aneurysms (PAAs) need urgent treatment in case of acute thrombosis, distal embolization, or rupture. Few data are available in the literature about the treatment results in these scenarios. The aim of the present study was to evaluate an 11-year multicenter experience in the urgent treatment of PAAs. METHODS: All symptomatic PAAs surgically treated in two vascular centers between 2010 and 2021 were retrospectively analyzed. In the postoperative period periodical clinical and Duplex-Ultrasound evaluation were performed. The evaluated endpoint was the outcome of urgent PAAs treatment according to their clinical presentation. Statistical analysis was performed by Kaplan-Meier log-rank evaluation and multivariable Cox regression tests. RESULTS: Sixty-six PAAs needed an urgent repair. Twelve (18%) patients had a PAA rupture and 54 (82%) had an acute limb ischemia (ALI) due to either distal embolization or acute thrombosis. Patients with ALI underwent bypass surgery in 51 (95%) cases, which was associated with preoperative thrombolysis in 18 (31%) cases. A primary major amputation was performed in 3 (5%) cases. The mean follow-up was 52 ± 21 months with an overall 5-year limb salvage of 83 ± 6%. Limb salvage was influenced only by the number of patent tibial arteries (pTA) [5-years limb salvage 0%, 86 ± 10%, 92 ± 8% and 100% in case of 0, 1, 2 or 3 pTA, respectively (P = .001)]. An independent association of number of pTA and limb loss was found [hazard ratio (HR): 0.14 (95% confidence interval (CI) 0.03-0.6), P = .001]. Overall 5-year survival was 71 ± 7%. Ruptured PAAs were associated with lower 5-year survival compared with the ALI group (48 ± 2% vs. 79 ± 7%, P = .001). The number of pTA (33 ± 20%, 65 ± 10%, 84 ± 10% and 80 ± 10% for 0, 1, 2 and 3 pTA, respectively, P = .001) and the thrombolysis (94 ± 6% vs. 62 ± 10%, P = .03) were associated with higher survival in patients with ALI. There was an independent association of number of pTA and long-term survival [HR 0.15 (95% CI 0.03-0.8), P = .03]. CONCLUSIONS: PAA rupture is the cause of urgent PAA treatment in almost one fifth of cases, and it is associated with lower long-term survival. ALI can benefit from thrombolysis, and long-term limb salvage and survival are associated with the number of pTA.

Machine perfusion techniques for liver transplantation - A meta-analysis of the first seven randomized-controlled trials.

BACKGROUND & AIMS: Machine perfusion is increasingly being tested in clinical transplantation. Despite this, the number of large prospective clinical trials remains limited. The aim of this study was to compare the impact of machine perfusion vs. static cold storage (SCS) on outcomes after liver transplantation. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted to identify randomized-controlled trials (RCTs) comparing "post-transplant" outcomes following machine perfusion vs. SCS. Data were pooled using random effect models. Risk ratios (RRs) were calculated for relevant outcomes. The quality of evidence was rated using the GRADE-framework. RESULTS: Seven RCTs were identified (four on hypothermic oxygenated [HOPE] and three on normothermic machine perfusion [NMP]), including a total number of 1,017 patients. Both techniques were associated with significantly lower rates of early allograft dysfunction (NMP: n = 41/282, SCS: n = 74/253, RR 0.50, 95% CI 0.30-0.86, p = 0.01, I2 = 39%; HOPE: n = 45/241, SCS: n = 97/241, RR 0.48, 95% CI 0.35-0.65, p < 0.00001, I2 = 5%). The HOPE approach led to a significant reduction in major complications (Clavien Grade ≥IIIb; HOPE: n = 90/241; SCS: n = 117/241, RR 0.76, 95% CI 0.63-0.93, p = 0.006, I2 = 0%), "re-transplantation" (HOPE: n = 1/163; SCS: n = 11/163; RR 0.21, 95% CI 0.04-0.96, p = 0.04; I2 = 0%) and graft loss (HOPE: n = 7/163; SCS: n = 19/163; RR 0.40, 95% CI 0.17-0.95, p = 0.04; I2 = 0%). Both perfusion techniques were found to 'likely' reduce overall biliary complications and non-anastomotic strictures. CONCLUSIONS: Although this study provides the highest current evidence on the role of machine perfusion, outcomes remain limited to a 1-year follow-up after liver transplantation. Comparative RCTs and large real-world cohort studies with longer follow-up are required to enhance the robustness of the data further, thereby supporting the introduction of perfusion technologies into routine clinical practice. PROSPERO-REGISTRATION: CRD42022355252. IMPACT AND IMPLICATIONS: For a decade, two dynamic perfusion concepts have increasingly been tested in several transplant centres worldwide. We undertook the first systematic review and meta-analysis and identified seven published RCTs, including 1,017 patients, evaluating the effect of machine perfusion (hypothermic and normothermic perfusion techniques) compared to static cold storage in liver transplantation. Both perfusion techniques were associated with lower rates of early allograft dysfunction in the first week after liver transplantation. Hypothermic oxygenated perfusion led to a reduction in major complications, lower "re-transplantation" rates and better graft survival. Both perfusion strategies were found to 'likely' reduce overall biliary complications and non-anastomotic biliary strictures. This study provides the highest current evidence on the role of machine perfusion. Outcomes remain limited to a 1-year post-transplant follow-up. Larger cohort studies with longer follow-up and clinical trials comparing the perfusion techniques are required. This is especially relevant to provide clarity and optimise implementation processes further to support the commissioning of this technology worldwide.

Renal Benefits of CO2 as a Contrast Media for EVAR Procedures: New Perspectives on 1 Year Outcomes.

BACKGROUND AND OBJECTIVES: Endovascular aneurism repair (EVAR) is a minimally invasive alternative to open surgery for the treatment of abdominal aortic aneurysm. Iodine contrast medium (ICM) is considered the gold standard, at the high price of related nephrotoxicity and allergic reactions. Carbon dioxide (CO2) has been suggested as an alternative non-nephrotoxic contrast media agent. We aimed to evaluate the safety and the renal impact of the administration of CO2, compared with ICM in EVAR procedures. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We retrospectively reviewed data of patients who underwent EVAR at the Vascular Surgery Department of the Sant'Orsola Hospital in Bologna. Estimated glomerular filtration rate (eGFR) was evaluated before intervention, immediately after and at 12 months. RESULTS: In total, 22 patients received CO2 and low-dose ICM (CO2 Group) and 22 received standard ICM (Control Group), matched for clinical characteristics and renal function at the time of procedure. Pre and post-operative renal function values (eGFR) were compared between the two groups: in the immediate post-operative the group treated with CO2 and low-dose ICM globally showed a slight improvement in renal function (mean eGFR +5.10%±3.2), meanwhile the group treated with standard dose of ICM presented a significant worsening of renal function compared with pre-procedure values (mean eGFR -9.65%±4). Incidence of post-contrast acute kidney injury (PC-AKI) was 9% in the CO2 group vs 27% in the Control group. At 12 months, the renal impairment was significantly greater in the ICM group than in the CO2 group (mean eGFR decrease -19.2%±11.1 and -7.40%±3.5, respectively). CONCLUSIONS: Administration of either CO2 alone or along with low-dose ICM showed to be safer than full-dose ICM alone, lowering the incidence of PC-AKI in patients undergoing EVAR. Unexpectedly, our study revealed also a significant worsening of renal function in patients treated with standard dose of ICM in 1-year follow-up, introducing the concept that acute renal damage caused by ICM could elicit a chronic injury process that affect long-term renal outcomes. CLINICAL IMPACT: Evaluating the safety and the renal impact of the administration of CO2, compared to Iodinate Contrast Medium, in EVAR procedures represents a first step in order to further tayloring medical procedures on patients characteristics. Our findings can guide the clinicians and surgeons in the procedures choice, not considering only the immediate effect of ICM on renal function but also the potential long-term effects.

Revascularisation of Chronic Limb Threatening Ischaemia in Patients with no Pedal Arteries Leads to Lower Midterm Limb Salvage.

OBJECTIVE: Chronic limb threatening ischaemia (CLTI) involving the infragenicular arteries is treated by distal angioplasty or pedal bypass; however, this is not always possible, due to chronically occluded pedal arteries (no patent pedal artery, N-PPA). This pattern represents a hurdle to successful revascularisation, which must be limited to the proximal arteries. The aim of the study was to analyse the outcome of patients with CLTI and N-PPA after a proximal revascularisation. METHODS: All patients with CLTI submitted to revascularisation in a single centre (2019 - 2020) were analysed. All angiograms were reviewed to identify N-PPA, defined as total obstruction of all pedal arteries. Revascularisation was performed with proximal surgical, endovascular, and hybrid procedures. Early and midterm survival, wound healing, limb salvage, and patency rates were compared between N-PPA and patients with one or more patent pedal artery (PPA). RESULTS: Two hundred and eighteen procedures were performed. One hundred and forty of 218 (64.2%) patients were male, mean age 73.2 ± 10.6 years. The procedure was surgical in 64/218 (29.4%) cases, endovascular in 138/218 (63.3%), and hybrid in 16/218 (7.3%). N-PPA was present in 60/218 (27.5%) cases. Eleven of 60 (18.3%) cases were treated surgically, 43/60 (71.7%) by endovascular and 6/60 (10%) by hybrid procedures. Technical success was similar in the two groups (N-PPA 85% vs. PPA 82.3%, p = .42). At a mean follow up of 24.5 ± 10.2 months, survival (N-PPA 93.7 ± 3.5% vs. PPA 95.3 ± 2.1%, p = .22) and primary patency (N-PPA 53.1 ± 8.1% vs. PPA 55.2 ± 5%, p = .56) were similar. Limb salvage was significantly lower in N-PPA patients (N-PPA 71.4 ± 6.6% vs. PPA 81.5 ± 3.4%, p = .042); N-PPA was an independent predictor of major amputation (hazard ratio [HR] 2.02, 1.07 - 3.82, p = .038) together with age > 73 years (HR 2.32, 1.17 - 4.57, p = .012) and haemodialysis (2.84, 1.48 - 5.43, p = .002). CONCLUSION: N-PPA is not uncommon in patients with CLTI. This condition does not hamper technical success, primary patency, and midterm survival; however, midterm limb salvage is significantly lower than in patients with PPA. This should be considered in the decision making process.

Tissue Ki67 proliferative index expression and pathological changes in hemodialysis arteriovenous fistulae: Preliminary single-center results.

BACKGROUND: Arteriovenous fistula (AVF) for hemodialysis integrates outward remodeling with vessel wall thickening in response to drastic hemodynamic changes. Aim of this study is to determine the role of Ki67, a well-established proliferative marker, related to AVF, and its relationship with time-dependent histological morphologic changes. MATERIALS AND METHODS: All patients were enrolled in 1 year and stratified in two groups: (A) pre-dialysis patients submitted to first AVF and (B) patients submitted to revision of AVF. Morphological changes: neo-angiogenesis (NAG), myointimal thickening (MIT), inflammatory infiltrate (IT), and aneurysmatic fistula degeneration (AD). The time of AVF creation was recorded. A biopsy of native vein in Group A and of arterialized vein in Group B was submitted to histological and immunohistochemical (IHC) analysis. IHC for Ki67 was automatically performed in all specimens. Ki67 immunoreactivity was assessed as the mean number of positive cells on several high-power fields, counted in the hot spots. RESULTS: A total of 138 patients were enrolled, 69 (50.0%) Group A and 69 (50.0%) Group B. No NAG or MIT were found in Group A. Seven (10.1%) Group A veins showed a mild MIT. Analyzing the Group B, a moderate-to-severe MIT was present in 35 (50.7%), IT in 19 (27.5%), NAG in 37 (53.6%); AD was present in 10 (14.5%). All AVF of Group B with the exception of one (1.4%) showed a positivity for Ki67, with a mean of 12.31 ± 13.79 positive cells/hot spot (range 0-65). Ki67-immunoreactive cells had a subendothelial localization in 23 (33.3%) cases, a myointimal localization in SMC in 35 (50.7%) cases. The number of positive cells was significantly correlated with subendothelial localization of Ki67 (p = 0.001) and with NA (p = 0.001). CONCLUSIONS: Native veins do not contain cycling cells. In contrast, vascular cell proliferation starts immediately after AVF creation and persists independently of the time the fistula is set up. The amount of proliferating cells is significantly associated with MIT and subendothelial localization of Ki67-immunoreactive cells, thus suggesting a role of Ki-67 index in predicting AVF failure.

Outcomes of radiocephalic arteriovenous fistula in octogenarians.

BACKGROUND: Current guidelines recommend radiocephalic arteriovenous fistula (RCAVF) as a first choice access for hemodialysis, without specific indication for octogenarians .This study was undertaken to assess the efficacy of RCAVF in octogenarians compared with younger patients. MATERIAL AND METHODS: All patients treated by RCAVF from January 2013 to December 2017 were included in a prospective database for a retrospective analysis. Patient demographics, comorbidities, and dialytic treatment data were collected prospectively and compared in patients <80 year-old and ⩾80 years-old. Clinical surveillance was performed during each dialysis session. The main endpoints were primary (PP) and assisted patency (AP). RESULTS: Within the study period, a total of 294 RCAVF were analyzed: 245 (83.3%) RCAVF were performed in <80 year-old and 49 (16.7%) ⩾80 years old. The overall PP and AP at 2-year was 69% ± 2% and 73% ± 3%, respectively. Patients ⩾ 80 years-old had a significantly reduced 2-year PP, AP of RCAVF compared with the younger patients: 50% ± 8% and 62% ± 7% versus 73% ± 3% and 75% ± 3%, p = 0.01 and p = 0.03, respectively.The analysis for possible risk factors for reduction of PP in patients ⩾80 years identified in the central venous catheter(CVC) a predictor of earlier RCAVF failure: HR 3.03(95% CI 1.29-7.13), p = 0.01.Kaplan-Meier curve confirms the reduction of PP in ⩾80 years old patients at 2-year follow-up with previous CVC compared patients without history of CVC: 59% ± 10% versus 24% ± 11%, p = 0.01. A comparison between the two groups was made in order to evaluate the impact of previous history of CVC .In absence of a history of CVC use older patients had a similar 2-year PP compared with younger patients: 59% ± 10% versus 72% ± 4%, p = 0.46. Otherwise, the history of a previous CVC reduced significantly the 2-year PP in ⩾80 years old patients compared the younger: 24% ± 12% versus 75% ± 5%, p = 0.0001. CONCLUSIONS: Despite lower overall primary and primary assisted patency, RCAVF are associated with satisfactory results also in octogenarians if performed in absence of history of CVC. Under these circumstances RCAVF can be considered a first choice treatment.

Domain selection and familywise error rate for functional data: A unified framework.

Functional data are smooth, often continuous, random curves, which can be seen as an extreme case of multivariate data with infinite dimensionality. Just as componentwise inference for multivariate data naturally performs feature selection, subsetwise inference for functional data performs domain selection. In this paper, we present a unified testing framework for domain selection on populations of functional data. In detail, p-values of hypothesis tests performed on pointwise evaluations of functional data are suitably adjusted for providing control of the familywise error rate (FWER) over a family of subsets of the domain. We show that several state-of-the-art domain selection methods fit within this framework and differ from each other by the choice of the family over which the control of the FWER is provided. In the existing literature, these families are always defined a priori. In this work, we also propose a novel approach, coined thresholdwise testing, in which the family of subsets is instead built in a data-driven fashion. The method seamlessly generalizes to multidimensional domains in contrast to methods based on a priori defined families. We provide theoretical results with respect to consistency and control of the FWER for the methods within the unified framework. We illustrate the performance of the methods within the unified framework on simulated and real data examples and compare their performance with other existing methods.

Anastomotic Pseudoaneurysm in Kidney Transplant: A Challenging Management for a Rare Entity.

PURPOSE: Anastomotic pseudoaneurysms of transplanted kidneys are a very rare complication encountered in less than 1% of cases. They may be devastating, leading to functional impairment, kidney transplantectomy, or death. Treatment has not been standardized, with open surgical repair considered the safest procedure even if it is often complicated by bleeding and graft loss. The purpose of this case report is to describe an endovascular treatment of this condition, consisting of the combination of coil embolization and arterial stenting. CASE REPORT: A 61-year-old woman developed an anastomotic pseudoaneurysm 2 months after kidney transplantation, causing acute kidney injury related to ab-extrinsic stenosis of the transplant renal artery (TRA) and external iliac artery. The pseudoaneurysm was successfully treated by coil embolization, and the arterial patency was restored by the stenting of TRA and external iliac artery. The patient completely recovered kidney function, and after a 6-month-follow-up, creatinine values were stable with normal renal perfusion. CONCLUSION: Endovascular repair through coil embolization and TRA stenting can be a safe and effective option to treat anastomotic pseudoaneurysm in kidney transplant.

Assessment and Management of Transplant Renal Artery Stenosis. A Literature Review.

BACKGROUND: Transplant renal artery stenosis (TRAS) following kidney transplantation is a possible cause of graft failure. This review aimed to summarize the evidence about physiopathology, diagnosis and early and late effectiveness of the endovascular treatment (EVT), including angioplasty and stenting procedures. METHODS: A literature research was performed using Pubmed, Scopus and the Cochrane Library databases (January 2000-September 2020) according to PRISMA guidelines. Studies were included if they describe EVT, percutaneous transluminal angioplasty or stent placement of TRAS, published in English and with a minimum of ten patients. RESULTS: Fifty-six studies were included. TRAS incidence ranges from 1% up to 12% in transplanted kidneys. The TRAS risk factors were: elderly donor and recipient, cytomegalovirus match status, Class II Donor Specific Antibodies (DSA), expanded donor criteria, delayed graft functioning and other anatomical and technical factors. The highest frequency of TRAS presentation is after 3-6 months after kidney transplantation. The most frequent localization of stenosis was para-anastomotic (ranging from 25% to 78%). In 9 studies, all patients were treated by percutaneous transluminal angioplasty (PTA), in 16 studies all patients received percutaneous transluminal stenting (PTS) and in 21 series patients received either PTA or PTS. The twelve months patency rates after EVT ranged from 72% to 94%. The overall complication rate was 9%, with pseudoaneurysms and hematomas as most frequent complications. CONCLUSIONS: TRAS can be successfully and safely treated through an endovascular approach. Stent delivery seems to guarantee a higher patency rate compared to simple angioplasty, however further studies are needed to confirm these results.

Test-retest reliability measures for curve data: an overview with recommendations and supplementary code.

The purpose of this paper is to provide an overview of available methods for reliability investigations when the outcome of interest is a curve. Curve data, or functional data, is commonly collected in biomechanical research in order to better understand different aspects of human movement. Using recent statistical developments, curve data can be analysed in its most detailed form, as functions. However, an overview of appropriate statistical methods for assessing reliability of curve data is lacking. A review of contemporary literature of reliability measures for curve data within the fields of biomechanics and statistics identified the following methods: coefficient of multiple correlation, functional limits of agreement, measures of distance and similarity, and integrated pointwise indices (an extension of univariate reliability measures to curve data, inclusive of Pearson correlation, intraclass correlation, and standard error of measurement). These methods are briefly presented, implemented (R-code available as supplementary material) and evaluated on simulated data to highlight advantages and disadvantages of the methods. Among the identified methods, the integrated intraclass correlation and standard error of measurement are recommended. These methods are straightforward to implement, enable results over the domain, and consider variation between individuals, which the other methods partly neglect.

Test-retest reliability of entire time-series data from hip, knee and ankle kinematics and kinetics during one-leg hops for distance: Analyses using integrated pointwise indices.

Motion capture systems enable in-depth interpretations of human movements based on data from three-dimensional joint angles and moments. Such analyses carry important bearings for evaluation of movement control during for instance hop landings among sports-active individuals from a performance perspective but also in rehabilitation. Recent statistical development allows analysis of entire time-series of angle and moment during hops using functional data analysis, but the reliability of such multifaceted data is not established. We used integrated pointwise indices (intra-class correlation, ICC; standard error of measurement, SEM) to establish the test-retest reliability of three-dimensional hip, knee and ankle angle and moment curves during landings of one-leg hop for distance (OLHD) in 23 asymptomatic individuals aged 18-28. We contrasted these findings to reliability of discrete variables extracted at specific events (initial contact, peak value). We extended the calculations of ICC and SEM to handle unbalanced situations (varying number of repetitions) to include all available data. Hip and knee angle curves proved reliable with stable ICC curves throughout the landing, with integrated ICCs ≥ 0.71 for all planes except for knee internal/external rotation (ICC = 0.57). Hip and knee moment curves and ankle angle and moments were less reliable and less stable, particularly in the first ~ 10-25% of the landing (integrated ICCs 0.44-0.57). Curve data were generally not in agreement with the results for discrete event data, thus advocating analysis of curve data which contains more information. To conclude, hip and knee angle curve data during OLHD landings can reliably be evaluated, while moment curves necessitate careful consideration.

Analysis Choices Impact Movement Evaluation: A Multi-Aspect Inferential Method Applied to Kinematic Curves of Vertical Hops in Knee-Injured and Asymptomatic Persons.

Three-dimensional human motion analysis provides in-depth understanding in order to optimize sports performance or rehabilitation following disease or injury. Recent developments of statistical methods for functional data allow for novel ways to analyze often complex biomechanical data. Even so, for such methods as well as for traditional well-established statistical methods, the interpretations of the results may be influenced by analysis choices made prior to the analysis. We evaluated the consequences of three such choices when comparing one-leg vertical hop (OLVH) performance in individuals who had ruptured their anterior cruciate ligament (ACL), to that of asymptomatic controls, and also athletes. Kinematic data were analyzed using a statistical approach for functional data, targeting entire curve data. This was done not only for one joint at a time but also for multiple lower limb joints and movement planes simultaneously using a multi-aspect methodology, testing for group differences while also accounting for covariates. We present the results of when an individual representative curve out of three available was either: (1) a mean curve (Mean), (2) a curve from the highest hop (Max), or (3) a curve describing the variability (Var), as a representation of performance stability. We also evaluated choice of sample leg comparison; e.g., ACL-injured leg compared to either the dominant or non-dominant leg of asymptomatic groups. Finally, we explored potential outcome effects of different combinations of included joints. There were slightly more pronounced group differences when using Mean compared to Max, while the specifics of the observed differences depended on the outcome variable. For Var there were less significant group differences. Generally, there were more disparities throughout the hop movement when comparing the injured leg to the dominant leg of controls, resulting in e.g., group differences for trunk and ankle kinematics, for both Mean and Max. When the injured leg was instead compared to the non-dominant leg of controls, there were trunk, hip and knee joint differences. For a more stringent comparison, we suggest considering to compare the injured leg to the non-dominant leg. Finally, the multiple-joint analyses were coherent with the single-joint analyses. The direct effects of analysis choices can be explored interactively by the reader in the Supplementary Material. To summarize, the choices definitively have an impact on the interpretation of a hop test results commonly used in rehabilitation following knee injuries. We therefore strongly recommend well-documented methodological analysis choices with regards to comparisons and representative values of the measures of interests.

The Role of Ex Situ Hypothermic Oxygenated Machine Perfusion and Cold Preservation Time in Extended Criteria Donation After Circulatory Death and Donation After Brain Death.

Hypothermic oxygenated machine perfusion (HOPE) has the potential to counterbalance the detrimental consequences of cold and warm ischemia time (WIT) in both donation after brain death (DBD) and donation after circulatory death (DCD). Herein we investigated the protective effects of HOPE in extended criteria donor (ECD) DBD and overextended WIT DCD grafts. The present retrospective case series included 50 livers subjected to end-ischemic HOPE or dual DHOPE in 2 liver transplantation (LT) centers from January 2018 to December 2019. All DCD donors were subjected to normothermic regional perfusion before organ procurement. Results are expressed as median (interquartile range [IQR]). In the study period, 21 grafts were derived from overextended WIT DCD donors (total WIT 54 [IQR, 40-60] minutes and 75% classified as futile), whereas 29 were from ECD DBD. A total of 3 biliary complications and 1 case of ischemia-type biliary lesion were diagnosed. The rate of early allograft dysfunction (EAD) was 20%, and those patients had higher Comprehensive Complication Index scores. Through a changing point analysis, cold preservation time >9 hours was associated with prolonged hospital stays (P = 0.02), higher rates of EAD (P = 0.009), and worst post-LT complications (P = 0.02). Logistic regression analyses indicated a significant relationship between cold preservation time and EAD. No differences were shown in terms of the early post-LT results between LTs performed with DCD and DBD. Overall, our data are fully comparable with benchmark criteria in LT. In conclusion, the application of DHOPE obtained satisfactory and promising results using ECD-DBD and overextended DCD grafts. Our findings indicate the need to reduce cold preservation time also in the setting of DHOPE, particularly for grafts showing poor quality.

Kissing Stent Technique for TASC C-D Lesions of Common Iliac Arteries: Clinical and Anatomical Predictors of Outcome.

BACKGROUND: The endovascular treatment of peripheral artery obstructive disease in Trans-Atlantic Inter-Society (TASC) C and D lesions involving the aortic bifurcation is a matter of debate. The aim of this study is to evaluate the technical and clinical success of kissing stenting in this context and to analyze predictors of outcome. METHODS: All patients treated for aortoiliac TASC C and D lesions with kissing stenting (from 2012 to 2017) in a 6-year period were retrospectively analyzed. Preoperative anatomical features were evaluated by reviewing computed tomography angiography images to identify severe iliac calcifications (SICs) versus not SIC (NSICs). Primary end points were as follows: technical success (TS), procedural success, primary patency (PP), and clinical success (CS). Secondary end points were as follows: secondary patency, assisted patency, survival, mid-term procedure-related complications, and risk factors that affected TS and mid-term results. RESULTS: In a 6-year period, 51 patients fulfilled the inclusion criteria. TS was achieved in 49 (96.1%) cases. Thirty-one patients (60.8%) received a dual antiplatelet therapy (DAPT) for at least 1 month after the procedure. 30-day CS was 94.1%. Median follow-up was 45.7 months (IQR: 24.5, 8-86 range). The CS was 92.6% at 3 years, with a PP of 86.8% and a secondary patency of 93.2% at 3 years. Six (13.2%) iliac axis occluded during the first follow-up year. NSIC was statistically and independently associated with a lower PP (73% vs. 96%, P = 0.03); DAPT was statistically and independently associated with higher PP than single antiplatelet therapy (96% vs. 75%, P = 0.03); these results were confirmed by Cox regression analysis (HR: 0.14, 95%, IC: 0.01-0.89, P = 0.05 for DAPT analysis; HR: 6.8, 95%, IC: 1.21-59, P = 0.05 for NSIC analysis). CONCLUSIONS: Endovascular treatment for TASC C-D is an effective technique. Postoperative stent occlusion is higher in patients with no DAPT and it usually occurs during the first postoperative year. Preoperative NSIC lesions are associated with reduced PP at 3 years of follow-up.

New Graph-Theoretical-Multimodal Approach Using Temporal and Structural Correlations Reveals Disruption in the Thalamo-Cortical Network in Patients with Schizophrenia.

Schizophrenia has been understood as a network disease with altered functional and structural connectivity in multiple brain networks compatible to the extremely broad spectrum of psychopathological, cognitive, and behavioral symptoms in this disorder. When building brain networks, functional and structural networks are typically modeled independently: Functional network models are based on temporal correlations among brain regions, whereas structural network models are based on anatomical characteristics. Combining both features may give rise to more realistic and reliable models of brain networks. In this study, we applied a new flexible graph-theoretical-multimodal model called FD (F, the functional connectivity matrix, and D, the structural matrix) to construct brain networks combining functional, structural, and topological information of magnetic resonance imaging (MRI) measurements (structural and resting-state imaging) to patients with schizophrenia (n = 35) and matched healthy individuals (n = 41). As a reference condition, the traditional pure functional connectivity (pFC) analysis was carried out. By using the FD model, we found disrupted connectivity in the thalamo-cortical network in schizophrenic patients, whereas the pFC model failed to extract group differences after multiple comparison correction. We interpret this observation as evidence that the FD model is superior to conventional connectivity analysis, by stressing relevant features of the whole-brain connectivity, including functional, structural, and topological signatures. The FD model can be used in future research to model subtle alterations of functional and structural connectivity, resulting in pronounced clinical syndromes and major psychiatric disorders. Lastly, FD is not limited to the analysis of resting-state functional MRI, and it can be applied to electro-encephalography, magneto-encephalography, etc.

Exploring resting-state functional connectivity invariants across the lifespan in healthy people by means of a recently proposed graph theoretical model.

In this paper we investigate the changes in the functional connectivity intensity, and some related properties, in healthy people, across the life span and at resting state. For the explicit computation of the functional connectivity we exploit a recently proposed model, that bases not only on the correlations data provided by the acquisition equipment, but also on different parameters, such as the anatomical distances between nodes and their degrees. The leading purpose of the paper is to show that the proposed approach is able to recover the main aspects of resting state condition known from the available literature, as well as to suggest new insights, perspectives and speculations from a neurobiological point of view. Our study involves 133 subjects, both males and females of different ages, with no evidence of neurological diseases or systemic disorders. First, we show how the model applies to the sample, where the subjects are grouped into 28 different groups (14 of males and 14 of females), according to their age. This leads to the construction of two graphs (one for males and one for females), that can be realistically interpreted as representative of the neural network during the resting state. Second, following the idea that the brain network is better understood by focusing on specific nodes having a kind of centrality, we refine the two output graphs by introducing a new metric that favours the selection of nodes having higher degrees. As a third step, we extensively comment and discuss the obtained results. In particular, it is remarkable that, despite a great overlapping exists between the outcomes concerning males and females, some intriguing differences appear. This motivates a deeper local investigation, which represents the fourth part of the paper, carried out through a thorough statistical analysis. As a result, we are enabled to support that, for two special age groups, a few links contribute in differentiating the behaviour of males and females. In addition, we performed an average-based comparison between the proposed model and the traditional statistical correlation-based approach, then discussing and commenting the main outlined discrepancies.

IWTomics: testing high-resolution sequence-based 'Omics' data at multiple locations and scales.

Summary: With increased generation of high-resolution sequence-based 'Omics' data, detecting statistically significant effects at different genomic locations and scales has become key to addressing several scientific questions. IWTomics is an R/Bioconductor package (integrated in Galaxy) that, exploiting sophisticated Functional Data Analysis techniques (i.e. statistical techniques that deal with the analysis of curves), allows users to pre-process, visualize and test these data at multiple locations and scales. The package provides a friendly, flexible and complete workflow that can be employed in many genomic and epigenomic applications. Availability and implementation: IWTomics is freely available at the Bioconductor website (http://bioconductor.org/packages/IWTomics) and on the main Galaxy instance (https://usegalaxy.org/). Supplementary information: Supplementary data are available at Bioinformatics online.

Integration and Fixation Preferences of Human and Mouse Endogenous Retroviruses Uncovered with Functional Data Analysis.

Endogenous retroviruses (ERVs), the remnants of retroviral infections in the germ line, occupy ~8% and ~10% of the human and mouse genomes, respectively, and affect their structure, evolution, and function. Yet we still have a limited understanding of how the genomic landscape influences integration and fixation of ERVs. Here we conducted a genome-wide study of the most recently active ERVs in the human and mouse genome. We investigated 826 fixed and 1,065 in vitro HERV-Ks in human, and 1,624 fixed and 242 polymorphic ETns, as well as 3,964 fixed and 1,986 polymorphic IAPs, in mouse. We quantitated >40 human and mouse genomic features (e.g., non-B DNA structure, recombination rates, and histone modifications) in ±32 kb of these ERVs' integration sites and in control regions, and analyzed them using Functional Data Analysis (FDA) methodology. In one of the first applications of FDA in genomics, we identified genomic scales and locations at which these features display their influence, and how they work in concert, to provide signals essential for integration and fixation of ERVs. The investigation of ERVs of different evolutionary ages (young in vitro and polymorphic ERVs, older fixed ERVs) allowed us to disentangle integration vs. fixation preferences. As a result of these analyses, we built a comprehensive model explaining the uneven distribution of ERVs along the genome. We found that ERVs integrate in late-replicating AT-rich regions with abundant microsatellites, mirror repeats, and repressive histone marks. Regions favoring fixation are depleted of genes and evolutionarily conserved elements, and have low recombination rates, reflecting the effects of purifying selection and ectopic recombination removing ERVs from the genome. In addition to providing these biological insights, our study demonstrates the power of exploiting multiple scales and localization with FDA. These powerful techniques are expected to be applicable to many other genomic investigations.