A Convolutional-Transformer Model for FFR and iFR Assessment From Coronary Angiography.

The quantification of stenosis severity from X-ray catheter angiography is a challenging task. Indeed, this requires to fully understand the lesion's geometry by analyzing dynamics of the contrast material, only relying on visual observation by clinicians. To support decision making for cardiac intervention, we propose a hybrid CNN-Transformer model for the assessment of angiography-based non-invasive fractional flow-reserve (FFR) and instantaneous wave-free ratio (iFR) of intermediate coronary stenosis. Our approach predicts whether a coronary artery stenosis is hemodynamically significant and provides direct FFR and iFR estimates. This is achieved through a combination of regression and classification branches that forces the model to focus on the cut-off region of FFR (around 0.8 FFR value), which is highly critical for decision-making. We also propose a spatio-temporal factorization mechanisms that redesigns the transformer's self-attention mechanism to capture both local spatial and temporal interactions between vessel geometry, blood flow dynamics, and lesion morphology. The proposed method achieves state-of-the-art performance on a dataset of 778 exams from 389 patients. Unlike existing methods, our approach employs a single angiography view and does not require knowledge of the key frame; supervision at training time is provided by a classification loss (based on a threshold of the FFR/iFR values) and a regression loss for direct estimation. Finally, the analysis of model interpretability and calibration shows that, in spite of the complexity of angiographic imaging data, our method can robustly identify the location of the stenosis and correlate prediction uncertainty to the provided output scores.

Neural Transformers for Intraductal Papillary Mucosal Neoplasms (IPMN) Classification in MRI images.

Early detection of precancerous cysts or neoplasms, i.e., Intraductal Papillary Mucosal Neoplasms (IPMN), in pancreas is a challenging and complex task, and it may lead to a more favourable outcome. Once detected, grading IPMNs accurately is also necessary, since low-risk IPMNs can be under surveillance program, while high-risk IPMNs have to be surgically resected before they turn into cancer. Current standards (Fukuoka and others) for IPMN classification show significant intra- and inter-operator variability, beside being error-prone, making a proper diagnosis unreliable. The established progress in artificial intelligence, through the deep learning paradigm, may provide a key tool for an effective support to medical decision for pancreatic cancer. In this work, we follow this trend, by proposing a novel AI-based IPMN classifier that leverages the recent success of transformer networks in generalizing across a wide variety of tasks, including vision ones. We specifically show that our transformer-based model exploits pre-training better than standard convolutional neural networks, thus supporting the sought architectural universalism of transformers in vision, including the medical image domain and it allows for a better interpretation of the obtained results.

Deep learning for automated skeletal bone age assessment in X-ray images.

Skeletal bone age assessment is a common clinical practice to investigate endocrinology, genetic and growth disorders in children. It is generally performed by radiological examination of the left hand by using either the Greulich and Pyle (G&P) method or the Tanner-Whitehouse (TW) one. However, both clinical procedures show several limitations, from the examination effort of radiologists to (most importantly) significant intra- and inter-operator variability. To address these problems, several automated approaches (especially relying on the TW method) have been proposed; nevertheless, none of them has been proved able to generalize to different races, age ranges and genders. In this paper, we propose and test several deep learning approaches to assess skeletal bone age automatically; the results showed an average discrepancy between manual and automatic evaluation of about 0.8 years, which is state-of-the-art performance. Furthermore, this is the first automated skeletal bone age assessment work tested on a public dataset and for all age ranges, races and genders, for which the source code is available, thus representing an exhaustive baseline for future research in the field. Beside the specific application scenario, this paper aims at providing answers to more general questions about deep learning on medical images: from the comparison between deep-learned features and manually-crafted ones, to the usage of deep-learning methods trained on general imagery for medical problems, to how to train a CNN with few images.

Patients attitudes towards sleep disturbances during chemotherapy.

Sleep disturbances are among the most distressing symptoms in cancer: they often co-occur with fatigue, pain and psychological distress. Despite the negative impact on quality of life, patients rarely seek help for managing their sleep disturbances. This paper presents the results of a multicentre observational study on patients' attitudes towards their sleep problems. The study also investigates symptom correlates. Patients responded to a semi-structured interview and completed the following questionnaires: Pittsburgh Sleep Quality Index; Brief Fatigue Inventory; Hospital Anxiety and Depression Scale; and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life QLQ-C30 Questionnaire (QLQ-C30). Four hundred and three cancer patients were enrolled in the study. Bad sleepers constituted 66% of the sample. Thirty-eight per cent of them had not turned to any professional to solve their sleep disturbances because they had various beliefs about the importance of the problem and the possibility to be treated. The main correlates of sleep disturbances were psychological distress, reduced physical functioning and reduced overall quality of life. In conclusion, there is a need to sensitise patients to actively search for a solution to their sleep disturbances so they can be solved along with other co-occurring symptoms. Doctors could also be encouraged to dedicate more attention to routinely asking cancer patients about eventual sleep disturbances.

Effects of ischemia-reperfusion injury in kidney transplantation: risk factors and early and long-term outcomes in a single center.

INTRODUCTION: Ischemia-reperfusion injury (IRI) causes a high rate of delayed graft function (DGF), the most frequent complication in the immediate postoperative period after cadaveric donor kidney transplantation. Herein we evaluated the impact of donor and recipient characteristics on DGF development in terms of the incidence of acute rejection episodes, hospital stay, renal function, and long-term graft and patient survivals. MATERIALS AND METHODS: Between February 1998 and July 2011, 761 patients underwent cadaveric donor kidney transplantations. DGF was defined as the need for dialysis in the first week. Patients were subdivided according to initial graft function as immediate graft function (IGF) or DGF. RESULTS: DGF observed in 241 patients (31.6%) was associated independently with expanded criteria donors, extended cold ischemia time, Karpinsky histological score, and prior dialysis duration both univariate and multivariate analysis. The incidence of acute rejection episodes was 18.1% among the DGF group versus 1.3% in the IGF group (P < .01). DGF significantly reduced both graft and patient survivals at 6, 12, 36, and 60 months. CONCLUSION: DGF was responsible for a longer hospital stay, worse early and long-term renal function, a higher incidence of acute rejection episodes as well as reduced graft and patient survivals.

Pressure changes during tracheal suctioning--a laboratory study.

Suctioning is essential in managing tracheal tubes, but also has drawbacks. Using a bench model, we demonstrated the extent and time course of pressure changes during suctioning, examined their relationship with tracheal tube and catheter diameters and assessed the effects of artificial 'sputum' and of compensatory gas flow in the system. We suctioned at -20 kPa (-150 mmHg) and -80 kPa (-600 mmHg) using three different sized catheters and a 5.9-mm diameter bronchoscope through tracheal tubes ranging from 6.5 mm to 9.0 mm in diameter. Pressure changes ranged from -0.1 kPa (-0.8 mmHg) to -20.4 kPa (-153.0 mmHg). We demonstrated more negative pressures with decreasing tracheal tube diameter (p = 0.024) and increasing catheter diameter (p = 0.038). Addition of artificial 'sputum' led to more negative, but unpredictable, pressures than those seen with clean tubes (p = 0.012). Bronchoscopic suctioning produced pressure changes even greater than the largest suction catheter (p = 0.0039). Using a closed system with continuous positive airway pressure and 155 l.min(-1) compensatory gas flow attenuated the pressure changes generated both with a 4.0-mm catheter (p = 0.0005) and on bronchoscopic suctioning (p = 0.0078). The time taken to reach 50% of minimum pressure was always less than 1 s. The use of high compensatory flows during suctioning merits clinical evaluation.

Middle and long-term outcomes of dual kidney transplant: a multicenter experience.

INTRODUCTION: Dual kidney transplantation (DKTx) to reduce the disparity between demand and supply of organs was evaluated in two Italian centers (Bari and Novara). MATERIALS AND METHODS: Between October 2000 and October 2011, we performed 97 DKT (26 ipsilateral/71 bilateral) following routine biopsy of all kidneys obtained from expanded criteria donors by Remuzzi-Karpinsky scores. The reference group was 379 single grafts from donors older than 60 years single kidney transplantation ([SKT] × > 60). RESULTS: Good postoperative renal function was observed in 56 DKTx (57.7%); whereas acute tubular necrosis requiring dialysis was observed in 41 (42.3%) patients. After a mean follow-up of 60 months, DKTx graft survivals were 96%, 93%, and 90% and patient survivals, 96%, 91%, and 91% at 1, 3, and 5 years, respectively. Complications in expanded criteria donor kidney transplantations included a high rate of cytomegalovirus (CMV) disease especially dual kidney cases. DKTx represented the only independent risk factor for CMV disease upon multivariate analysis (odds ratio [OR] 2.33, 95% confidence interval [CI] 1.28-4.2; P = .006). We did not observe any significant difference in graft or patient survival between DKTx and SKTx > 60 years. CONCLUSIONS: We observed good outcomes up to 5 years after transplantation in terms of graft and patient survival despite the use of inferior grafts. Comparing DKTx and SKT > 60, we noted that the mean Karpinski score for SKTx was significantly better than DKTx, although patient and graft survivals were similar. This trend confirms that the use of a biopsy to allocate expanded criteria donor kidneys may be too protective; therefore, the criteria to select DKTx require further refinement.

[Ibuprofen versus steroids: risk and benefit, efficacy and safety]. / Ibuprofene e cortisone a confronto: rischio e beneficio di utilizzo in termini di efficacia e safety.

In the last few years we have observed an upward trend in the employment of ibuprofen as anti-inflammatory and antipyretic therapy. Therefore the pediatrician has often a precious option in the anti-inflammatory and antipyretic treatment in children instead of using steroids and paracetamol. In clinical practice ibuprofen can be used in the treatment of headache, toothache, otalgy, dysmenorrhea, neuralgia, arthralgia, myalgia, abdominal pain and fever: it is the first choice for these common diseases. However, the use of steroids is a routine, even if non-corticosteroid anti-inflammatory molecules could be useful. Certainly steroids are powerful anti-inflammatory, indicated for the treatment of chronic inflammatory disorders and in acute respiratory and allergic diseases. Beside, thanks to their chemical and pharmacological profile, they also provide patients with an antipyretic effect. However, the use of steroids must be reserved to cases in which other classical antipyretics such as non-steroidal anti-inflammatory drugs are not effective. The possible side effects and risks associated with stepping down steroids must be considered. Although "steroids-phobia" should be discouraged, steroids are to be reserved only as the first indication. In all other cases the pediatrician can use ibuprofen, whose efficacy and safety are widely demonstrated by now.

[Primary ciliary dyskinesia: clinical and genetic aspects]. / Discinesia ciliare primitiva: aspetti clinici e genetici.

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disease, characterized by ciliary disfunction and impaired mucociliary clearance, resulting in a range of clinical manifestations such as chronic bronchitis, bronchiectasis, chronic rhino-sinusitis, chronic otitis media, situs viscerum inversus in almost 40-50% of cases and male infertility. The triad situs viscerum inversus, bronchiectasis and sinusitis is known as Kartagener syndrome. Up to now little is known about genetic, diagnostic and therapeutic aspects of primary motile ciliary diseases in children: for this reason, diagnosis is generally delayed and almost all treatments for PCD are not based on randomized studies but extrapolated from cystic fibrosis guidelines. The aim of this review is to propose to pediatricians a summary of current clinical and diagnostic evidence to obtain better knoledwge of this condition. The earlier diagnosis and the right treatment are both crucial to improve the prognosis of PCD.

Allograft nephrectomy: what is the best surgical technique?

BACKGROUND: The objective of this study was to evaluate differences in outcomes of allograft nephrectomies performed by extracapsular versus intracapsular techniques. METHODS: From 1993 to 2010, we performed 89 allograft nephrectomies, including 57 by extracapsular techniques and 32 by intracapsular, chosen according to feasibility at the beginning of the surgery. Fisher exact test and logistic regression were used for statistical analysis. Survival estimates after allograft nephrectomy were calculated according to the Kaplan-Meier method. RESULTS: After a mean graft survival of 49.7 months, the indications for transplant nephrectomy were chronic rejection (39.3%), acute rejection (22.5%), infection/sepsis (19.1%), gross hematuria (6.7%), renal vein thrombosis (6.7%), renal artery thrombosis (3.4%), and graft rupture (2.3%). Mean operative time, blood loss, transfusions, and complications were similar between the extracapsular and intracapsular groups. The only difference in surgical aspects between the 2 groups was the mean hospital stay, which was longer for the extracapsular group (13.8 vs 7.6 days; P = .01), a result that was confirmed by multivariate analysis (odds ratio, 1.05; 95% confidence interval, 1.0-1.1; P = .03). CONCLUSIONS: Our experience showed no significant advantages in favor of the intracapsular technique except for a shorter length of hospital stay than after the extracapsular procedure.

Image processing with cellular nonlinear networks implemented on field-programmable gate arrays for real-time applications in nuclear fusion.

In the past years cameras have become increasingly common tools in scientific applications. They are now quite systematically used in magnetic confinement fusion, to the point that infrared imaging is starting to be used systematically for real-time machine protection in major devices. However, in order to guarantee that the control system can always react rapidly in case of critical situations, the time required for the processing of the images must be as predictable as possible. The approach described in this paper combines the new computational paradigm of cellular nonlinear networks (CNNs) with field-programmable gate arrays and has been tested in an application for the detection of hot spots on the plasma facing components in JET. The developed system is able to perform real-time hot spot recognition, by processing the image stream captured by JET wide angle infrared camera, with the guarantee that computational time is constant and deterministic. The statistical results obtained from a quite extensive set of examples show that this solution approximates very well an ad hoc serial software algorithm, with no false or missed alarms and an almost perfect overlapping of alarm intervals. The computational time can be reduced to a millisecond time scale for 8 bit 496560-sized images. Moreover, in our implementation, the computational time, besides being deterministic, is practically independent of the number of iterations performed by the CNN-unlike software CNN implementations.

Patients' perspectives on how doctors dress.

Infection in hospitals is a serious problem. Attempting to address the spread of infection, many UK National Health Service trusts have adopted a 'bare-below-the-elbows' and tie-less dress-code policy. This followed publication of Department of Health guidelines on staff uniforms in September 2007. Although the potential for colonisation of clothing with pathogens has been investigated, patients' opinions on dress-code and policy change have not. This survey of 75 patients in Great Western Hospital, Swindon, UK, used questionnaires to address this. The survey showed that, although patients did feel that doctors' dress was important, neckties and white coats were not expected. Moreover, surgical scrubs were considered acceptable forms of attire. Problems of identifying doctors and determining their grade were repeatedly raised. Patients were generally unaware of the new dress-code, and few knew anything of its relationship to infection control. This work demonstrates that more 'traditional' dress is not expected. Given the problems of identification and perception of surgical scrubs as suitable, their introduction as a 'uniform for doctors' should be considered. Furthermore, work needs to be done to advertise policy change and increase patient awareness of infection control.

"Deviceless" hand-assisted laparoscopic donor nephrectomy.

Hand-assisted laparoscopic nephrectomy (HLN) in living donors is a minimally invasive surgical modality that uses classic laparoscopic techniques combined with the surgeon's hand as a support tool during renal dissection. We describe our experience with 14 donors undergoing HLN with a novel "deviceless" technique (DL-HLN). We used a midline or a paramedian incision. The first 10-mm trocar (camera) was inserted near the umbilicus and another 10-mm trocar placed under laparoscopic vision at the level of the anterior axillary line above the iliac crest. DL-HLN was performed in 14 patients (11 women and 3 men) of overall mean age of 40 years (range=33-60). Left nephrectomy was performed in all cases. Mean surgical time was 105 minutes (range=60-150). Estimated blood loss was 50 to 800 mL (mean=200 mL). Mean warm ischemia time was 3.5 minutes (range=2-11). Mean hospital stay was 4 days (range=3-6). In one case, uncontrollable hemorrhage developed due to a renal vein lesion at the level of the adrenal vein outlet, requiring conversion to open surgery. As to graft function, recipient serum creatinine on day 7 ranged from 0.9 to 2.6 mg/dL (mean=1.6). We used no device in our technique. The pneumoperitoneum was maintained by the sealing effect of the muscular fascia around the surgeon's wrist. Moreover, the kidney was removed through the hand port without an Endobag. Our modified HLN technique avoids the use of costly disposables and offers the advantages of a smaller incision.

Incidentally discovered yellowish lesions in a renal graft from a deceased donor.

The opening of Gerota's fascia, soon after harvesting the kidney, is a standard kidney donor procedure in Italy to exclude a renal cell carcinoma (RCC), a frequent finding in older donors. Herein we have reported our experience with the diagnosis and management of subcapsular yellow areas suggestive of RCC on the kidney surface during back-table procedures. From 2001 to 2006, 12/445 grafts showed a single yellowish subcapsular nodule during the back-table procedure which was excised for frozen section (FS) to rule out RCC. The affected donors were 7 males and 5 females of overall mean age of 60 years (range, 25-77 years). The mean nodule diameter was 0.75 cm (range, 0.3-1.2 cm), and all lesions were located in the upper renal pole. In 5 cases, a diagnosis of RCC could not be excluded by FS, and both kidneys were discarded. The final histology confirmed RCC in only 3 cases, and adrenal heterotopia (AH) in the other 2. In the remaining 7 cases, FS showed AH in 4, 1 angiomyolipoma, and 2 areas of infarction confirmed by histology. The adrenal foci consisted of clear cells and scattered cells with eosinophilic, granular cytoplasm and small round nuclei, some with small nucleoli. Immunostains for cytokeratins, CD10, and epithelial membrane antigen were negative, confirming the adrenal origin. AH is the most common pathological yellowish lesion in the upper kidney pole found incidentally during back-table preparation. A histological differential diagnosis with RCC at FS is difficult, relying on the distinction of normal corticoadrenal spongiocytes from Fuhrman grade 1 clear cancer cells. In Italy, for any renal mass suggestive of RCC, a graft discard is mandatory, even if several reports have described cases of renal transplantation performed after back-table excision of small unifocal tumors.

Ischemia-reperfusion injury-induced abnormal dendritic cell traffic in the transplanted kidney with delayed graft function.

Delayed graft function (DGF) in kidney transplantation is associated with an increased risk of acute rejection. Myeloid dendritic cells (DCs) are involved in graft rejection, whereas plasmacytoid DCs may play a role in inducing tolerance. We evaluated the presence and phenotype of the DCs in renal graft biopsies of 15 patients with DGF collected before and 7-15 days after transplantation. Biopsies taken from normal patients and from transplant recipients with acute calcineurin inhibitors (CNIs) nephrotoxicity served as a control group. Specific markers of myeloid, plasmacytoid, and mature DCs were imaged by confocal microscopy and immunohistochemistry. In normal kidneys and pre-transplant biopsies, sparse niches of myeloid and plasmacytoid cells were found but these were significantly increased with few mature cells during DGF. This same pattern was seen in acute rejection but with overall higher cell numbers. In CNI nephrotoxicity, myeloid cells were slightly increased but plasmacytoid cells were significantly higher than in DGF. Using a pig model, we found that a short period of warm ischemia followed by reperfusion led to myeloid cell infiltration of the kidney. Our data suggest that ischemia-reperfusion injury may cause an imbalance between intragraft myeloid and plasmacytoid DCs, which might be related to DGF and acute rejection.

Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study.

The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival advantage. The hazard ratio (HR) of relapse was 0.89 (95% confidence intervals (CI): 0.73-1.09) for patients receiving FA and 0.99 (95% CI 0.80-1.21) for those receiving LEV; corresponding HRs of death were 1.02 (95% CI: 0.80-1.30) and 0.94 (95% CI 0.73-1.20). Nonhaematological toxicity (all grade vomiting, diarrhoea, mucositis, congiuntivitis, skin, fever and fatigue) was significantly worse with FA, while all other toxicities were similar. In the present trial, there was no evidence that the addition of FA or LEV significantly prolongs DFS and OAS of radically resected colorectal cancer patients.

Double J stent with antireflux device in the prevention of short-term urological complications after cadaveric kidney transplantation: single-center prospective randomized study.

The placement of a double J stent to protect a uretero-vesical anastomosis in a kidney transplant is a widespread procedure performed to reduce the incidence of fistula and stenosis at the anastomosis. However, the presence of a double J stent may cause vesicoureteral reflux (VUR), predisposing one to urinary tract infections (UTIs), which may be a significant source of morbidity for the graft. We evaluated whether a ureteral stent incorporating an antireflux device can reduce the incidence of ureteral reflux and UTIs. From January to December 2003, 44 kidney transplant recipients were randomized to receive a 14-cm 4.8-F double J stent with (group A) or without an anti-reflux device (group B). Primary end points were the reduction of the incidence of VUR and of UTIs. The secondary end point was the graft function, on the basis of mean serum creatinine level at 3, 6, and 12 months. We failed to observe statistically significant differences in terms of either the incidence of VUR and UTIs, or the short-term outcomes of the grafts. We concluded that the anti-reflux device does not have an impact on the incidence of stent-related side effects.

A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer.

The sequential doxorubicin --> CMF (CMF=cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF x 6 cycles (CMF); (b) doxorubicin x 4 cycles followed by CMF x 6 cycles (A --> CMF); (c) CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (CMF --> GT); and (d) doxorubicin x 4 cycles followed by CMF x 6 cycles followed by goserelin plus tamoxifen x 2 years (A --> CMF --> GT). The study used a 2 x 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A --> CMF or arms a+c vs b+d) and (2) the effect of adding GT after chemotherapy (arms a+b vs c+d). At a median follow-up of 72 months, A --> CMF as compared to CMF significantly improved disease-free survival (DFS) with a multivariate hazard ratio (HR)=0.740 (95% confidence interval (CI): 0.556-0.986; P=0.040) and produced a nonsignificant improvement of overall survival (OS) (HR=0.764; 95% CI: 0.489-1.193). The addition of GT after chemotherapy significantly improved DFS (HR=0.74; 95% CI: 0.555-0.987; P=0.040), with a nonsignificant improvement of OS (HR=0.84; 95% CI: 0.54-1.32). A --> CMF is superior to CMF. Adding GT after chemotherapy is beneficial for premenopausal node-positive patients.

Kidney transplants from infected donors: our experience.

Organ procurement from infected donors may transmit a disease to the recipient that could cause a graft loss and/or recipient morbidity. Retrospectively, all kidney transplants from infected donors at our center in the last 4 years were reviewed. A donor was considered infected in the presence of at least one positive culture before procurement. From January 1999 to 2003, 23 of 160 donors (14.5%) were infected: in 10 donors a positive blood culture; in 3, a urine culture; and in 13, a bronchial culture. In a further 12 (7%) donors, only the preservation solution was contaminated. Organisms isolated were: Staphylococcus coagulase.neg. (n = 7); Staphylococcus epidermidis (n = 3); Staphylococcus aureus (n = 6); Klebsiella pneumoniae (n = 3); Pseudomonas aeruginosa (n = 4); Acinetobacter (n = 1); Candida albicans (n = 13); Aspergillus (n = 1); and Escherichia coli (n = 1). All except 2 kidneys were transplanted with positivity in all cultures. All recipients received general, nonspecific, antibacterial and antifungal prophylaxis until the antibiotic and antifungal spectrum was ready. Patient and graft survival rates at 6 months were 94% and 93%, respectively. Two deaths occurred due to bacterial arteritis (P aeruginosa), and 2 acute graft losses due to fungal arteritis. Kidneys from infected donors seem suitable for transplants. Only grafts infected by vasculotropic agents (S aureus, P aeruginosa, and C albicans) should be discarded.