A multi-step approach to overcome challenges in the management of head and neck lymphatic malformations, and response to treatment.

BACKGROUND: Lymphatic malformations are vascular developmental anomalies varying from local superficial masses to diffuse infiltrating lesions, resulting in disfigurement. Patients' outcomes range from spontaneous regression to severe sequelae notwithstanding appropriate treatment. The current classification guides, in part, clinicians through the decision-making process, prognosis prediction and choice of therapeutic strategies. Even though the understanding of molecular basis of the disease has been recently improved, a standardized management algorithm has not been reached yet. RESULTS: Here, we report our experience on five children with different lymphatic anomalies of the head and neck region treated by applying a multidisciplinary approach reaching a consensus among specialists on problem-solving and setting priorities. CONCLUSIONS: Although restitutio ad integrum was rarely achieved and the burden of care is challenging for patients, caregivers and healthcare providers, this study demonstrates how the referral to expert centres can significantly improve outcomes by alleviating parental stress and ameliorating patients' quality of life. A flow-chart is proposed to guide the multidisciplinary care of children with LMs and to encourage multidisciplinary collaborative initiatives to implement dedicated patients' pathways.

Influence of intercostal muscles contraction on sonographic evaluation of lung sliding: a physiological study on healthy subjects.

OBJECTIVES: To investigate the following: (a) effects of intercostal muscle contraction on sonographic assessment of lung sliding and (b) inter-rater and intra-observer agreement on sonographic detection of lung sliding and lung pulse. METHODS: We used Valsalva and Muller maneuvers as experimental models in which closed glottis and clipped nose prevent air from entering the lungs, despite sustained intercostal muscles contraction. Twenty-one healthy volunteers underwent bilateral lung ultrasound during tidal breathing, apnea, hyperventilation, and Muller and Valsalva maneuvers. The same expert recorded 420 B-mode clips and 420 M-mode images, independently evaluated for the presence or absence of lung sliding and lung pulse by three raters unaware of the respiratory activity corresponding to each imaging. RESULTS: During Muller and Valsalva maneuvers, lung sliding was certainly recognized in up to 73.0% and up to 68.7% of imaging, respectively, with a slight to fair inter-rater agreement for Muller maneuver and slight to moderate for Valsalva. Lung sliding was unrecognized in up to 42.0% of tidal breathing imaging, and up to 12.5% of hyperventilation imaging, with a slight to fair inter-rater agreement for both. During apnea, interpretation errors for sliding were irrelevant and inter-rater agreement moderate to perfect. Even if intra-observer agreement varied among raters and throughout respiratory patterns, we found it to be higher than inter-rater reliability. CONCLUSIONS: Intercostal muscles contraction produces sonographic artifacts that may simulate lung sliding. Clinical studies are needed to confirm this hypothesis. We found slight to moderate inter-rater agreement and globally moderate to almost perfect intra-observer agreement for lung sliding and lung pulse. TRIAL REGISTRATION: ClinicalTrials.gov registration number. NCT02386696.

Clinical Correlates of In-Hospital Mortality in Patients Undergoing Inferior Vena Cava Filter Placement for Acute Deep Vein Thrombosis.

Background: It is reasonable to place an Inferior Vena Cava Filter (IVCF) when an acute deep vein thrombosis (DVT) of the lower limbs occurs in a patient with absolute contraindication to therapeutic anticoagulation. An additional potential reason for placing an IVCF is the need to stop therapeutic anticoagulation in a patient with acute DVT who must undergo urgent non-deferrable surgery. However, IVCFs are often used outside of such established indications and many authors argue about their actual utility, especially in terms of survival. In this retrospective study, we looked for clinical correlates of in-hospital mortality among patients who underwent IVCF placement, limiting our analysis to the cases for which a correct indication to IVCF placement existed. Methods: We retrospectively analyzed the electronic database of our University Hospital, searching for consecutive hospitalized patients who had acute DVT and underwent IVCF placement because of an established contraindication to therapeutic anticoagulation and/or because it was necessary to stop anticoagulation due to urgent surgery. The search covered the period between 1 January 2010 and 31 December 2020. Results: The search resulted in the identification of 168 individuals. An established contraindication to therapeutic anticoagulation was present in 116 patients (69.0%), while urgent non-deferrable surgery was the reason for IVCF placement in 52 patients (31.0%). A total of 24 patients (14.3%) died during the same hospital stay in which the IVCF was placed. Mortality rate was significantly higher in patients with a contraindication to anticoagulation than in patients who underwent IVCF placement because of urgent surgery (19.0% vs. 3.8%, OD 5.85 vs. 0.17). In-hospital mortality was also significantly higher among patients with chronic kidney disease and those who needed blood cell transfusion during hospitalization. Conclusions: This study provides novel information on clinical correlates of in-hospital mortality among patients with acute DVT who undergo IVCF. Prospective observational studies are needed to substantiate these findings.

Interventional Radiology in the Treatment of Pancreatic Adenocarcinoma: Present and Future Perspectives.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease; patients' long-term survival is strictly linked to the surgical resection of the tumor but only a minority of patients (2-3%) have a resectable disease at diagnosis. In patients with surgically unresectable disease, interventional radiology is taking on an increasing role in treatment with the application of loco-regional percutaneous therapies. The primary purposes of this narrative review are to analyze the safety and efficacy of ablative techniques in the management of borderline resectable and locally advanced diseases and to underline the role of the interventional radiologist in the management of patients with distant metastases. The secondary purpose is to focus on the synergy between immunotherapy and ablative therapies.

Value of transrectal color Doppler ultrasound of the common penile arteries in the diagnosis of arteriogenic erectile dysfunction: A pilot study.

BACKGROUND: Penile duplex Doppler ultrasound in combination with intra-cavernous injection of vasoactive agents (PDDU-ICI) is the most accepted tool for diagnosis of arteriogenic erectile dysfunction (AED), but is invasive, time consuming and at risk of side effects. OBJECTIVES: The purpose of this pilot study is to evaluate the potential of transrectal color Doppler ultrasound (TR-CDU) of the common penile arteries as a non-invasive method for the diagnosis of AED. MATERIALS AND METHODS: A consecutive series of 61 men consulting for erectile dysfunction (ED) and 20 controls underwent TR-CDU examination, aged from 40 to 80 years. Sonographic parameters were correlated with the International Index of Erectile Function, short form (IIEF-5). Sensitivity and specificity were calculated and the areas under the receiver operating characteristic curves (AUC) were compared to evaluate the diagnostic performance. RESULTS: Receiver operating characteristic curve analysis showed no significant results for IIEF-5 score ⩾21 in relation to the Doppler parameters. However, we found a good diagnostic performance for patients with ED grading from moderate to severe at IIEF-5. In this cohort, we found that mean peak systolic velocity >15.8 cm/s predicted IIEF-5 ⩾17 (AUC = 0.73, p = 0.002) with 61.5% sensitivity and 85.7% specificity. Mean end diastolic velocity >1.46 cm/s predicted IIEF-5 ⩾17 (AUC = 0.68, p = 0.02) with 80.7% sensitivity and 52.4% specificity. Mean resistance index ⩽0.72 predicted IIEF-5 ⩾17 (AUC = 0.71, p = 0.004) with 46.2% sensitivity and 95.2% specificity. Mean pulsatility index ⩽1.41 predicted IIEF-5 ⩾17 (AUC = 0.75, p = 0.0005) with 48.5% sensitivity and 95.14% specificity. CONCLUSIONS: TR-CDU proved to be a feasible and non-invasive procedure, easily repeatable and not time consuming, overcoming the limits of PDDU-ICI. Diagnostic accuracy seems to be promising in discriminating patients with normal erectile function or mild dysfunction from those with moderate to severe ED. However, these findings need to be verified in future controlled randomized clinical trials.

Supine versus Prone 3D Abus Accuracy in Breast Tumor Size Evaluation.

Breast-conserving surgery (BCS) with negative resection margins decreases the locoregional recurrence rate. Breast cancer size is one of the main determinants of Tumor-Node-Metastasis (TNM) staging. Our study aimed to investigate the accuracy of supine 3D automated breast ultrasound (3D ABUS) compared to prone 3D ABUS in the evaluation of tumor size in breast cancer patient candidates for BCS. In this prospective two-center study (Groups 1 and 2), we enrolled patients with percutaneous biopsy-proven early-stage breast cancer, in the period between June 2019 and May 2020. Patients underwent hand-held ultrasound (HHUS), contrast-enhanced magnetic resonance imaging (CE-MRI) and 3D ABUS-supine 3D ABUS in Group 1 and prone 3D ABUS in Group 2. Histopathological examination (HE) was considered the reference standard. Bland-Altman analysis and plots were used. Eighty-eight patients were enrolled. Compared to prone, supine 3D ABUS showed better agreement with HE, with a slight tendency toward underestimation (mean difference of -2 mm). Supine 3D ABUS appears to be a useful tool and more accurate than HHUS in the staging of breast cancer.

Treatment of Early-Stage Gynecological Cancer-Related Lower Limb Lymphedema by Lymphaticovenular Anastomosis-The Triple Incision Approach.

Background and Objectives: Lower extremity lymphedema (LEL) is one of the most relevant chronic and disabling sequelae after gynecological cancer therapy involving pelvic lymphadenectomy (PL). Supermicrosurgical lymphaticovenular anastomosis (LVA) is a safe and effective procedure to treat LEL, particularly indicated in early-stage cases when conservative therapies are insufficient to control the swelling. Usually, preoperative assessment of these patients shows patent and peristaltic lymphatic vessels that can be mapped throughout the limb to plan the sites of skin incision to perform LVA. The aim of this study is to report the efficacy of our approach based on planning LVA in three areas of the lower limb in improving early-stage gynecological cancer-related lymphedema (GCRL) secondary to PL. Materials and Methods: We retrospectively reviewed the data of patients who underwent LVA for the treatment of early-stage GCRL following PL. Patients who had undergone groin dissection were excluded. Our preoperative study based on indocyanine green lymphography (ICG-L) and color doppler ultrasound (CDU) planned three incision sites located in the groin, in the medial surface of the distal third of the thigh, and in the upper half of the leg, to perform LVA. The primary outcome measure was the variation of the mean circumference of the limb after surgery. The changes between preoperative and postoperative limbs' measures were analyzed by Student's t-test. p values < 0.05 were considered significant. Results: Thirty-three patients were included. In every patient, three incision sites were employed to perform LVA. A total of 119 LVA were established, with an average of 3.6 for each patient. The mean circumference of the operated limb showed a significant reduction after surgery, decreasing from 37 cm ± 4.1 cm to 36.1 cm ± 4.4 (p < 0.01). Conclusions: Our results suggest that in patients affected by early-stage GCRL secondary to PL, the placement of incision sites in all the anatomical subunits of the lower limb is one of the key factors in achieving good results after LVA.

Optimizing the Angiography Protocol to Reduce Radiation Dose in Uterine Artery Embolization: The Impact of Digital Subtraction Angiographies on Radiation Exposure.

PURPOSE: The aim was to compare a protocol of uterine artery embolization (UAE) consisting in three digital subtraction angiographies (DSAs)-Group A, with a protocol based on a single DSA-Group B. MATERIALS AND METHODS: This is a single-center prospective randomized study enrolling 20 women (mean age 41 years, range 22-55 years) with uterine fibroids treated with UAE, from January 2015 to February 2016. All UAEs were performed by two interventional radiologists using the same angiography machine. Protocol of Group A consisted in three DSA runs (non-selective pelvic view and selective uterine views before and after embolization). Protocol of Group B consisted in 1 DSA run: selective UA angiography before embolization. (Fluoroscopic roadmap was used for UA catheterization; fluoroscopy storage was used as control after embolization.) Each patient was randomized to receive Protocol A in one pelvic side and Protocol B on the other. RESULTS: All patients received bilateral UAE. Mean fluoroscopy time for UA catheterization was 11.3 ± 3.7 s. (Protocol A) and 9.93 ± 2.99 s. (Protocol B) (p = 0.19). Fluoroscopy dose for catheterization and embolization was not different between both protocols (p = 0.14). Identification of the UA origin score was similar in both protocols (median error = 0, p = 0.79). Mean dose area product (DAP) was 40859 mGy/cm2 (Protocol A) and 28839 mGy/cm2 (Protocol B) (p = 0.003). Mean effective dose (ED) decreased from Protocol A (14.6 mSv) to Protocol B (9.2 mSv; - 37%). Mean absorbed dose (AD) to ovaries and uterus, respectively, decreased of 53% and 55% from Protocol A to Protocol B. CONCLUSION: Reducing the number of DSA runs from 3 to 1 during UAE allows at least a 30% reduction on radiation exposure, without compromising technical outcomes.

Sclerotherapy with polidocanol microfoam in head and neck venous and lymphatic malformations.

Objective: Polidocanol sclerotherapy of head and neck venous malformations (VMs) and lymphatic malformations (LMs) has been reported only in limited series. In this manuscript we evaluated the efficacy and safety of polidocanol sclerotherapy in a series of head and neck venous and lymphatic malformations. Methods: This retrospective observational study analysed data on 20 head and neck VMs and LMs that underwent to percutaneous or endoscopic intra-lesional 3% polidocanol microfoam sclerotherapy at our institution. Clinical response was ranked as excellent, moderate and poor based on volume reduction by MRI and resolution of symptoms. Results: The median volume decreased from 19.3 mL to 5.8 mL after sclerotherapy (mean volume reduction: 72.98 ± 16.1%). An excellent-moderate response was observed in 94.4% of cases. We observed a mean volume reduction of 79.5 ± 16.1 in macrocystic LMs, of 76.1 ± 13.0% in VMs, of 60.5 ± 10.9% in mixed lymphatic ones and 42.5% in microcystic lymphatic ones. Conclusions: Polidocanol sclerotherapy appears to be an effective and safe treatment for venous and lymphatic head and neck malformations. We observed the best responses in macrocystic LMs and VMs, whereas mixed lymphatic ones showed a moderate response and microcystic lymphatic ones a poor response.

European Society of Gynaecological Oncology guidelines for the peri-operative management of advanced ovarian cancer patients undergoing debulking surgery.

The European Society of Gynaecological Oncology (ESGO) developed and established for the first time in 2016, and updated in 2020, quality indicators for advanced ovarian cancer surgery to audit and improve clinical practice in Europe and beyond. As a sequela of the continuous effort to improve oncologic care in patients with ovarian cancer, ESGO issued in 2018 a consensus guidance jointly with the European Society of Medical Oncology addressing in a multidisciplinary fashion 20 selected key questions in the management of ovarian cancer, ranging from molecular pathology to palliation in primary and relapse disease. In order to complement the above achievements and consolidate the promoted systemic advances and surgical expertise with adequate peri-operative management, ESGO developed, as the next step, clinically relevant and evidence-based guidelines focusing on key aspects of peri-operative care and management of complications as part of its mission to improve the quality of care for women with advanced ovarian cancer and reduce iatrogenic morbidity. To do so, ESGO nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of ovarian cancer (18 experts across Europe). To ensure that the guidelines are evidence based, the literature published since 2015, identified from a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 117 independent international practitioners in cancer care delivery and patient representatives.

Dying "from" or "with" COVID-19 during the Pandemic: Medico-Legal Issues According to a Population Perspective.

There is still a lack of knowledge concerning the pathophysiology of death among COVID-19-deceased patients, and the question of whether a patient has died with or due to COVID-19 is still very much debated. In Italy, all deaths of patients who tested positive for SARS-CoV-2 are defined as COVID-19-related, without considering pre-existing diseases that may either contribute to or even cause death. Our study included nine subjects from two different nursing homes (Cases 1-4, Group A; Cases 5-9, Group B). The latter included patients who presumably died from CO poisoning due to a heating system malfunction. All subjects tested positive for COVID-19 both ante- and post-mortem and were examined using post-mortem computed tomography prior to autopsy. COVID-19 was determined to be a contributing cause in the deaths of four out of nine subjects (death due to COVID-19; i.e., pneumonia and sudden cardiac death). In the other five cases, for which CO poisoning was identified as the cause of death, the infection presumably had no role in exitus (death with COVID-19). In our attempt to classify our patients as dying with or due to COVID-19, we found the use of complete assessments (both histological analyses and computed tomography examination) fundamental.

Use of post-mortem chest computed tomography in Covid-19 pneumonia.

BACKGROUND AND AIM: COVID-19 is an extremely challenging disease, both from a clinical and forensic point of view, and performing autopsies of COVID-19 deceased requires adequately equipped sectorial rooms and exposes health professionals to the risk of contagion. Among one of the categories that are most affected by SARS-Cov-2 infection are the elderly residents. Despite the need for prompt diagnoses, which are essential to implement all isolation measures necessary to contain the infection spread, deceased subjects in long-term care facilities are still are often diagnosed post-mortem. In this context, our study focuses on the use of post-mortem computed tomography for the diagnosis of COVID-19 infection, in conjunction with post-mortem swabs. The aim of this study was to assess the usefulness of post-mortem whole CT-scanning in identifying COVID-19 pneumonia as a cause of death, by comparing chest CT-findings of confirmed COVID-19 fatalities to control cases. MATERIALS AND METHODS: The study included 24 deceased subjects: 13 subjects coming from long-term care facility and 11 subjects died at home. Whole body CT scans were performed within 48 h from death in all subjects to evaluate the presence and distribution of pulmonary abnormalities typical of COVID-19-pneumonia, including: ground-glass opacities (GGO), consolidation, and pleural effusion to confirm the post-mortem diagnosis. RESULTS: Whole-body CT scans was feasible and allowed a complete diagnosis in all subjects. In 9 (69%) of the 13 cases from long-term care facility the cause of death was severe COVID 19 pneumonia, while GGO were present in 100% of the study population. CONCLUSION: In the context of rapidly escalating COVID-19 outbreaks, given that laboratory tests for the novel coronavirus is time-consuming and can be falsely negative, the post-mortem CT can be considered as a reliable and safe modality to confirm COVID-19 pneumonia. This is especially true for specific postmortem chest CT-findings that are rather characteristic of COVID-19 fatalities.

Conventional CT versus Dedicated CT Angiography in DIEP Flap Planning: A Feasibility Study.

The deep inferior epigastric perforator (DIEP) flap is used with increasing frequency in post-mastectomy breast reconstruction. Preoperative mapping with CT angiography (CTa) is crucial in reducing surgical complications and optimizing surgical techniques. Our study's goal was to investigate the accuracy of conventional CT (cCT), performed during disease staging, compared to CTa in preoperative DIEP flap planning. In this retrospective, single-center study, we enrolled patients scheduled for mastectomy and DIEP flap breast reconstruction, subjected to cCT within 24 months after CTa. We included 35 patients in the study. cCT accuracy was 95% (CI 0.80-0.98) in assessing the three largest perforators, 100% (CI 0.89-100) in assessing the dominant perforator, 93% (CI 0.71-0.94) in assessing the perforator intramuscular course, and 90.6% (CI 0.79-0.98) in assessing superficial venous communications. Superficial inferior epigastric artery (SIEA) caliber was recognized in 90% of cases (CI 0.84-0.99), with an excellent assessment of superficial inferior epigastric vein (SIEV) integrity (96% of cases, CI 0.84-0.99), and a lower accuracy in the evaluation of deep inferior epigastric artery (DIEA) branching type (85% of cases, CI 0.69-0.93). The mean X-ray dose spared would have been 788 ± 255 mGy/cm. Our study shows that cCT is as accurate as CTa in DIEP flap surgery planning.

Diagnostic accuracy of resection margin in specimen radiography: digital breast tomosynthesis versus full-field digital mammography.

OBJECTIVE: We investigated the accuracy of digital breast tomosynthesis compared to full-field digital mammography for evaluating tumor-free resection margins in the intraoperative specimen during breast-conserving surgery, reducing re-excision rates. MATERIALS AND METHODS: In total, 170 patients, with proven breast cancer and eligible for breast-conserving surgery, were enrolled. Intraoperative specimens underwent digital mammography and digital breast tomosynthesis. Two breast radiologists, with ten years of experience in breast imaging, in batch mode, evaluated tumor-free resection margins and the distance between the margins and lesion. Histopathological findings were considered the standard of reference. RESULTS: We used the correlation analysis to evaluate the agreement between measures of tumor-free resection margins obtained with digital mammography and the true value (histopathological findings), and between digital breast tomosynthesis and histopathological findings. The size evaluation determined by digital breast tomosynthesis was more accurately correlated with that found by pathology; the calculated Pearson's correlation coefficient of digital breast tomosynthesis and digital mammography to the pathologically determined tumor-free resection margins were 0.92 and 0.79 in CC view and 0.92 and 0.72 in LL view, respectively. Compared with the pathologically determined tumor-free resection margins, the size determined by both imaging modalities was, on average, overestimated. Bland-Altman analysis showed an excellent inter readers agreement. CONCLUSIONS: Digital breast tomosynthesis is more accurate in assessment of margin status than digital mammography; it could be a more accurate technique than full-field digital mammography for the intraoperative delineating of tumor resection margins.

Uterine Myomas: Endovascular Treatment.

Uterine fibroids embolization is a safe and effective organ sparing treatment for fibroid-related symptoms based on a broad range of published evidence including randomized-controlled trials. Indication to treatment is usually the presence of symptomatic uterine fibroids. In this review, a systematic search of journal articles relevant to the treatment of symptomatic uterine fibroids was conducted, with a special focus on the indication to treatment, technique, procedural outcomes and pain control. All clinical trials published in English language, representing original research, and reporting clinical outcomes associated with interventions for the management of symptomatic uterine fibroids were considered.

Percutaneous transhepatic cholangioscopy using a single-operator cholangioscope (pSOC), a retrospective, observational, multicenter study.

BACKGROUND AND AIMS: Percutaneous cholangioscopy (PC) is more complex and invasive than a transpapillary approach, with the need for a large percutaneous tract of 16 French (Fr) on average in order to advance standard percutaneous cholangioscopes. The aim of this study was to investigate whether percutaneous single-operator cholangioscopy (pSOC) using the SpyGlass™ DS system is feasible, safe, and effective in PC for diagnostic and therapeutic indications. MATERIALS AND METHODS: The data of 28 patients who underwent pSOC in 4 tertiary referral centers were retrospectively analyzed. Technical and clinical success for therapeutic procedures was assessed as well as diagnostic accuracy of pSOC-guided biopsies and visualization. Adverse events and the required number and size of dilatations were reviewed. RESULTS: 25/28 (89%) patients had a post-surgical altered anatomy. The average number of percutaneous dilatations prior to pSOC was 1.25 with a mean dilatation size of 11 French. Histopathology showed a 100% accuracy. Visual impression showed an overall accuracy of 96.4%. Technical and clinical success was achieved in 27/28 (96%) of cases. Adverse events occurred in 3/28 (10.7%) cases. CONCLUSION: pSOC is a feasible, safe, and effective technique for diagnostic and therapeutic indications. It may be considered an alternative approach in clinical cases where gastrointestinal anatomy is altered. It has the potential to reduce peri-procedural adverse events and costs. Prospective randomized-controlled trials are necessary to confirm the previously collected data.

The usefulness of the IMAP propeller flap for trachea and tracheostome reconstruction after resection of parastomal recurrence of squamous cell carcinoma following salvage total laryngectomy.

PURPOSE: Parastomal recurrence of squamous cell carcinoma (SCC) with tracheal involvement following salvage total laryngectomy after prior concurrent chemoradiotherapy is one of the most insidious challenges in head and neck surgery because a complex reconstruction is often required for covering a large area of skin loss, filling the dead space beneath, tracheal reconstruction and suspension, and tracheostome resurfacing. The aim is to describe our experience with the internal mammary artery perforator (IMAP) propeller flap for tracheal and tracheostome reconstruction and neck resurfacing after parastomal and cervical trachea resection, especially for suspension and anchoring the stump of the residual distal trachea to the island flap itself. METHODS: We describe IMAP flap reconstruction after resection of parastomal recurrence of SCC requiring cervical trachea resection in five patients between January 1, 2005 and August 30, 2019. RESULTS: IMAP propeller flap was successfully used for reconstruction after complex resection of parastomal recurrence of SCC with cervical trachea involvement in all cases. The mean length and width were, respectively, 16.8 cm (range 13-23) and 6.9 cm (range 5.5-8). We did not report complications of both the donor and the recipient site. Pharyngo-cutaneous or tracheoesophageal fistulas and wound dehiscence were not observed. CONCLUSIONS: to the best of our knowledge, this is the first report about the use of the IMAP propeller flap in this more complex clinical setting and we provide the message that this surgical procedure is worthy of consideration.