A phase I/II clinical trial of ex-vivo expanded human bone marrow derived allogeneic mesenchymal stromal cells in adult patients with perianal fistulizing Crohn's Disease.

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn's disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population. METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn's disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model. RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time. CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing. TRIAL REGISTRATION: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

Laparoscopic ultrasonography along with staging laparoscopy as a tool for staging in patients with hepatopancreaticobiliary malignancy - A prospective cohort study from a tertiary care centre.

INTRODUCTION: Staging laparoscopy (SL) plays an important role in avoiding unnecessary non-therapeutic laparotomy in radiologically resectable hepatopancreaticobiliary (HPB) malignancy patients. The limitation of SL is to detect deep-seated malignancy. The addition of laparoscopic ultrasonography for identifying metastatic lesions or locally unresectable disease improves the diagnostic yield of SL. PATIENTS AND METHODS: This prospective, observational study was conducted in a single unit of the tertiary care centre between 2017 and 2019. All the patients of HPB malignancy who were radiologically resectable underwent SL and laparoscopic intraoperative ultrasonography. Metastatic disease patients were either underwent palliative bypass procedures or abandoned depending on the condition of the patient. Patients who had resectable disease underwent standard surgical procedures. RESULTS: Forty patients of HPB malignancy with potentially resectable on radiological imaging underwent SL and diagnostic ultrasonography. Out of 40, 21 patients had periampullary, 14 had carcinoma gallbladder and 5 patients had distal cholangiocarcinoma. Metastatic lesions were identified on laparoscopy in eight patients and the diagnostic yield of SL is 20%. Addition of laparoscopic ultrasonography identified one haemangioma which was false positive on laparoscopy and underwent the radical standard procedure. Four patients were unresectable so the procedure was abandoned and another three patients underwent a bypass procedure. CONCLUSION: Laparoscopic ultrasonography during SL can detect deep-seated metastatic lesions and decide the management in resectable disease.

Lessons learnt from the clinico-genomic profiling of families with Li Fraumeni syndrome at a tertiary care centre in North India.

Li Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome due to TP53 gene mutation. There is sparse literature on LFS in the Indian population. We conducted a retrospective study of patients diagnosed with LFS and their family members, registered at our Medical Oncology Department between September 2015 and 2022. 9 LFS families consisted of 29 patients diagnosed currently or historically with malignancies including 9 index cases and 20 first or second-degree relatives. Of these 29 patients, 7 (24.1%) patients developed their first malignancy before the age of 18 years, 15 (51.7%) were diagnosed between 18and and 60 years, and 7 (24.1%) were diagnosed at age more than 60 years. A total of 31 cancers occurred among the families, including 2 index cases who had metachronous malignancies. Each family had a median of three cancers (range 2-5); sarcoma (n = 12, 38.7% of total cancers) and breast cancer (n = 6, 19.3% of total cancers) being the commonest malignancies. Germline TP53 mutations were documented among 11 patients with cancers and 6 asymptomatic carriers. Of these nine mutations, the most common types were missense (n = 6, 66.6%) and nonsense (n = 2, 22.2%), and the commonest aberration was replacement of arginine with histidine (n = 4, 44.4%). Eight (88.8%) families met either classical or Chompret's diagnostic criteria and two (22.2%) satisfied both. Two (22.2%) families fit the diagnostic criteria prior to onset of malignancy in the index cases but were untested till the index cases presented to us. Four mutation carriers from three families are undergoing screening as per the Toronto protocol. No new malignancies have been detected so far during the mean surveillance duration of 14 months. The diagnosis of LFS has socio-economic implications for patients and their families. Delay in genetic testing misses out a crucial window wherein asymptomatic carriers could initiate surveillance in a timely fashion. Greater awareness on LFS and genetic testing in Indian patients is warranted for better management of this hereditary condition.

Imaging characteristics of phosphaturic mesenchymal tumors.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome associated with phosphaturic mesenchymal tumors (PMTs). Localization of the causative tumor in these cases is an arduous task since the culprit lesions are usually small, slow-growing, and can be located almost anywhere from head to toe. PURPOSE: To describe the morphological characteristics of histologically proven PMTs on various radiological modalities. MATERIAL AND METHODS: After institutional ethical approval, this retrospective study analyzed 20 cases with a histopathological evidence of PMT. Various imaging characteristics of the tumors on available computed tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated. Descriptive statistical analyses were conducted. RESULTS: The tumors were located in diverse locations: lower extremities (n = 10); head and neck (n = 5); vertebral column (n = 3); pelvis (n = 1); and upper extremities (n = 1). Bone lesions seen on CT had variable morphology: sclerotic (n = 3/8, 37.5%); lytic (n = 3/8, 37.5%), and both lytic and sclerotic (n = 2/8, 25%) with presence of narrow zone of transition in all cases (n = 8/8) and amorphous internal matrix calcifications in 25% of cases (n = 2/8). Of the tumors, 68.4% (n = 13/19) were hypointense on T1 and all of them showed hyperintense signal on T2-weighted and STIR images (n = 19/19) and contrast enhancement (n = 16/16). Of the tumors, 66.7% (n = 6/9) showed restricted diffusion. DOTANOC PET/CT showed tumor uptake in all cases (n = 8/8). CONCLUSION: PMTs may have variable and non-specific tumor appearances on various imaging modalities. However, in an appropriate clinical scenario and a background of suggestive biochemical work-up, the radiologist should keep a high index of suspicion.

Myotendinous pseudomasses: an imaging review.

A mass or a tumor may not always be an underlying cause for a clinically apparent swelling. A wide range of myotendinous disorders can present as pseudomasses. These include muscle/myofascial hernia, tendon tears, benign hypertrophy, accessory muscles, tendon xanthomas, diffuse myositis, and exertional compartment syndromes. We have briefly reviewed these lesions highlighting their typical radiological findings and have also highlighted the role of different imaging modalities and the role of dynamic imaging. Although rare, radiologists should be aware of these entities to avoid mislabeling a pseudomass as a mass or malignancy and to detect the abnormality in not-so-apparent masses.

Multimodality imaging evaluation of pseudotumors in chronic renal dysfunction: exposing the masquerade!

Focal renal lesions in the background of chronic kidney disease (CKD) present a diagnostic challenge. Contrast administration is usually avoided in such a setting, undermining the usefulness of computed tomography and magnetic resonance imaging. Focal regenerating nodules may occur in the background of CKD and closely mimic renal neoplasms. The aim of the present article was to highlight the salient manifestations of such CKD pseudotumors on different imaging modalities and also to depict the differentiating features from malignancy. Radiologists must be aware of the imaging appearance of this uncommonly talked about entity so as to avoid inadvertent surgery or cause undue anxiety to the patient.

Vascular anomalies: nomenclature, classification, and imaging algorithms.

There is a lot of ambiguity in the usage of correct terminology in the description of vascular malformations and tumors. Hemangioma and arteriovenous malformation (AVM) are the most commonly used terms and are the mostly incorrectly used as well! The aim of this review article was to lay out the correct nomenclature and describe the correct usage for the physicians and radiologists involved in diagnosing and managing these lesions. We describe the various classification systems which have been devised to define the multiple entities included under vascular anomalies. The latest classification system that should be adhered to is per the International Society for the Study of Vascular Anomalies, approved at the 20th ISSVA Workshop held in Melbourne in April 2014, last revised in May 2018. The main features of the latest revision have been highlighted. This classification, however, does not list the diagnostic clinico-radiological features for each entity. In addition, guidelines regarding the appropriate use of available imaging modalities are lacking in the literature. We, hereby, aim to address these pertinent issues in this review article.

Protocol for Developing a Femur Osteotomy Model in Wistar Albino Rats.

Fracture healing is a physiological process resulting in the regeneration of bone defects by the coordinated action of osteoblasts and osteoclasts. Osteoanabolic drugs have the potential to augment the repair of fractures but have constraints like high costs or undesirable side effects. The bone healing potential of a drug can initially be determined by in vitro studies, but in vivo studies are needed for the final proof of concept. Our objective was to develop a femur osteotomy rodent model that could help researchers understand the development of callus formation following fracture of the shaft of the femur and that could help establish whether a potential drug has bone healing properties. Adult male Wistar albino rats were used after Institutional Animal Ethics Committee clearance. The rodents were anesthetized, and under aseptic conditions, complete transverse fractures at the middle one-third of the shafts of the femurs were created using open osteotomy. The fractures were reduced and internally fixed using intramedullary K-wires, and secondary fracture healing was allowed to take place. After surgery, intraperitoneal analgesics and antibiotics were given for 5 days. Sequential weekly x-rays assessed callus formation. The rats were sacrificed based on radiologically pre-determined time points, and the development of the fracture callus was analyzed radiologically and using immunohistochemistry.

Osteoid Osteoma of Scaphoid Treated with Radiofrequency Ablation.

Osteoid osteoma is one of the commonest benign bone tumour of adolescence. Diagnosis is based upon the typical clinical features, site of occurrence and imaging findings. Occurrence of this lesion in an atypical site is associated with delay in diagnosis and challenges in management. We present a rare case of osteoid osteoma in scaphoid in a 14-year-old girl. Comprehensive work-up using radiograph, computerized tomography (CT), magnetic resonance imaging and Tc99-multidetector methylene diphosphonate (MDP) bone scan was used to make the correct diagnosis over other conditions with similar presentation like de Quervain tenosynovitis, intersection syndrome and inflammatory arthropathies. We also describe the treatment using CT-guided percutaneous radiofrequency ablation of this lesion and a brief literature review regarding the incidence of this lesion and treatment options available. Level of Evidence: Level V (Therapeutic).

Contrast enhanced ultrasound for characterization of suspected soft tissue vascular anomalies.

BACKGROUND: Evaluation of perfusion characteristics is the key to characterize vascular anomalies. Contrast-enhanced ultrasound (CEUS) is a radiation-free modality to evaluate this in real-time and can be coupled along with Doppler-ultrasound (US). OBJECTIVE: To evaluate the utility of CEUS in characterization of suspected soft-tissue vascular anomalies and compare its diagnostic accuracy with Doppler-US. MATERIALS AND METHODS: This was an ethically-approved cross-sectional study, done from November 2017- November 2019, involving 93 patients (55 M/38F; mean age 23.6 ± 11.9 years) in development cohort and 128 (66 M/62F; mean age 21.4 ± 11.1 years) in validation cohort. Patients suspected to have soft-tissue vascular anomalies on clinical evaluation and US were included. Clinical features, US, Doppler, subjective and quantitative CEUS features (from time-intensity curves) were evaluated. Composite gold standard employing MRI, phlebogram, DSA or biopsy was used to make the final diagnosis. The CEUS features found to be significantly different in the development cohort were prospectively validated in the validation cohort. P-value < 0.05 was considered significant, ROC curves were drawn and threshold values obtained for the various quantitative parameters. A prospective diagnosis was suggested in the validation group along with a degree of diagnostic confidence and accuracy was calculated. RESULTS: The spectrum of lesions included 77 venous malformations, 46 fibro-adipose vascular anomalies, 32 vascular tumors, 20 arteriovenous malformations and 20 lymphatic malformations. All lesions were found to have distinctive temporal and morphological subjective enhancement patterns. Quantitative parameters like rise-time, mean-transit-time, time-to-peak, peak-enhancement showed significant differences between the various groups (P value < 0.05). Addition of CEUS not only increased the diagnostic accuracy of Doppler-US from 76.5% (91/119) to 88.2% (105/119), but also the degree of diagnostic confidence in characterization of soft-tissue vascular anomalies. None of the patients showed any contrast-related adverse effects. CONCLUSION: Contrast-enhanced ultrasound is useful to characterize different types of soft-tissue vascular anomalies and increases the diagnostic accuracy and confidence over Doppler-ultrasound.

Chest-Wall Collateral Embolization to Reduce Surgical Blood Loss in Peripheral Aspergillomas.

OBJECTIVES: The objective of this study was to present the procedural details and digital subtraction angiography (DSA) findings of perioperative chest-wall collateral embolization (PCCE) and compare intraoperative blood loss in patients of pulmonary aspergilloma (PA) undergoing lung resection with and without PCCE. MATERIALS AND METHODS: Since November 2017, we have performed PCCE in 17 patients (14 males, three females, age 34.41 ± 12.85 years) before surgery for PA (embolization group). Retrospective evaluation of these patients was done, DSA findings were noted, and perioperative parameters (surgical approach, extent of resection, operative time, blood loss, blood transfusion, morbidity grade, and length of post-operative stay) were compared with a comparative cohort of 24 patients of PA (21 males, three females, mean age 36.13 ± 12.58 years) who underwent thoracic surgery without PCCE (May 2013-November 2017) (control group) using the Mann-Whitney U test. RESULTS: A total of 55 arteries were embolized in 17 patients (mean 3.23 arteries per patient). Technical success could be achieved in all patients without any procedure-related complications. The most common arteries embolized were posterior intercostal arteries (29) followed by costocervical trunk (10), superior thoracic (8), lateral thoracic (5), and internal thoracic arteries (3). The mean blood loss was significantly lower in the embolization group compared with the control group (676.47 vs. 1,264.58 mL, p = 0.015). Within the embolization group, patients who underwent video-assisted thoracoscopic surgery had even lower blood loss compared with open surgery cases (466 vs. 887.50 mL, p-value = 0.046). CONCLUSION: PCCE is a simple and safe procedure, useful in reducing intra-operative blood loss in patients undergoing surgery for peripherally located PA.

Unusual Primary Neoplasms of the Adult Liver: Review of Imaging Appearances and Differential Diagnosis.

The radiological appearance of common primary hepatic tumors such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) is widely recognized. Hepatic masses with unusual histology are occasionally encountered, but seldom suspected on imaging. However, many possess characteristic imaging findings, which when assessed along with the clinical and demographic background and serum tumor markers, may enable a prospective diagnosis. This review attempts to familiarize the reader with the clinicopathological characteristics, imaging manifestations, and differential diagnosis of these unusual liver tumors in adults. Biphenotypic primary liver carcinoma is suspected in masses showing distinct areas of HCC and CCA-type enhancement pattern in cirrhotic livers. Fibrolamellar carcinoma occurs in young individuals without underlying chronic liver disease and shows a characteristic T2-hypointense scar frequently showing calcification. Perivascular epithelioid cell tumors are differentials for any arterial hyperenhancing mass in the noncirrhotic liver, particularly in patients with tuberous sclerosis. Multifocal subcapsular tumors showing target-like morphology, capsular retraction and "lollipop" sign are suspicious for epithelioid hemangioendothelioma. On the other hand, multiple hemorrhagic lesions showing patchy areas of bizarre-shaped arterial phase hyperenhancement are suspicious for angiosarcoma. Primary hepatic lymphoma (PHL) is suspected when patients with immunosuppression present with solitary or multifocal masses that insinuate around vessels and bile ducts without causing luminal narrowing. Intense diffusion restriction and low-level homogeneous or target-like enhancement are also ancillary features of PHL. Primary hepatic neuroendocrine tumor shows uptake on Ga-68 DOTANOC PET/CT. Although a straightforward diagnosis may be difficult in these cases, awareness of the characteristic imaging appearances is helpful in suspecting the diagnosis.

Kimura Disease: A Case Series and Systematic Review of Clinico-radiological Features.

Kimura disease is a rare chronic inflammatory disorder mostly reported in males in second to third decades from south-east Asia. Head and neck is the most commonly involved region. The usual presentation is painless facial swelling with salivary gland involvement and regional lymphadenopathy. The diagnosis can be suspected on imaging but needs to be proven on histopathology. We describe three histopathology proven cases of Kimura disease and emphasize the specific clinic-radiological findings which can help in early identification of the condition and its differentiation from other diseases with similar presentation. Gray scale Ultrasound, contrast-enhanced ultrasound, and contrast-enhanced Magnetic Resonance Imaging (CE-MRI) were done in all patients and Computed Tomography (CT) was done in one. The salient imaging features were ill-defined solid mass in the subcutaneous location of the facial region which was heteroechoic on Gray scale Ultrasound, heterogeneously hyperintense on T2W MRI and without much diffusion restriction. There was involvement of salivary glands with ipsilateral cervical adenopathy. The lesion showed avid contrast enhancement on contrast-enhanced ultrasound and CE-MRI. We also present a systematic literature review of clinico-radiological features in Kimura disease in the head and neck. The articles with histopathologically proven cases and satisfactory description of imaging findings were included and we have compared the findings in our cases with published literature. In addition, we have included examples of radiological mimics of this disease. Certain imaging findings are highly suggestive and can aid in early diagnosis of Kimura disease which helps in early initiation of treatment with better patient prognosis.

Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis.

BACKGROUND/AIMS: Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. METHODS: Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. RESULTS: Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn's disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn's disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%. CONCLUSIONS: Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.

Is Pulley Reconstruction Better Than Pulley Release for De Quervain's Tenosynovitis? A Double-Blind Randomized Controlled Trial.

Purpose The aim of this study was to compare the results of surgeries of the De Quervain's disease (DQD) through a randomized control trial. Materials and Methods We treated 40 cases of De Quervain's tenosynovitis in 2 groups: 20 patients by pulley release method and another 20 patients by pulley reconstruction method. The patients were selected as per the random table number. The clinical data, numeric Visual Analogue Scale (VAS) score, Quick DASH-Disabilities of the Arm, Shoulder, and Hand-score, Mayo Wrist Score, and subluxation of the tendons in dynamic ultrasonography (USG) during wrist hyperflexion and abduction of the thumb test were noted preoperatively and 6 months after the operation. All patient charts were reviewed and data analysis was done after completion of the study. Results All patients improved after surgery. There was no difference in clinical outcome data, numeric VAS score, Quick DASH Score, and Mayo Wrist Score ( p -value > 0.05). There were four patients with tendon subluxation under USG in pulley release group, out of which only one patient was clinically symptomatic. There was no tendon subluxation in pulley reconstruction group. The tendon subluxation between the two groups was not found to be statistically significant ( p -value: 0.661). Conclusion Although, higher numbers of subluxation were found in release group, there was no statistically significant difference in the outcome of the two surgical procedures for DQD. This study is a pilot study, and it may act as the groundwork over which further studies may be performed. Level of Evidence This is a Level I study.

CT texture analysis in evaluation of thymic tumors and thymic hyperplasia: correlation with the international thymic malignancy interest group (ITMIG) stage and WHO grade.

OBJECTIVES: To evaluate the effectiveness of CT texture analysis (CTTA) in (1) differentiating Thymoma (THY) from thymic hyperplasia (TH) (2) low from high WHO grade, and (3) low from high Masaoka Koga (MK)/International Thymic Malignancy Interest Group (ITMIG) stages. METHODS: After institute ethical clearance, this cross-sectional study analyzed 26 patients (THY-18, TH-8) who underwent dual energy CT (DECT) and surgery between January 2016 and December 2018. CTTA was performed using TexRad (Feedback Medical Ltd., Cambridge, UK- www.fbkmed.com) by a single observer. Free hand regions of interest (ROIs) were placed over axial sections where there was maximum enhancement and homogeneity. Filtration histogram was used to generate six first-order texture parameters [mean, standard deviation (SD), mean of positive pixels (MPP), entropy, skewness, and kurtosis] at six spatial scaling factors "SSF 0, 2, 3, 4, 5, and 6". Mann-Whitney test was applied among various categories and p value < 0.05 was considered significant. Three-step feature selection was performed to determine the best parameters among each category. RESULTS: The best performing parameters were (1) THY vs TH- Mean at "SSF 0" (AUC: 0.8889) and MPP at "SSF 0" (AUC: 0.8889), (2) Low vs high WHO grade - no parameter showed statistical significance with good AUC, and (3) Low vs high MK/ITMIG stage- SD at "SSF 6" (AUC: 0.8052 and 0.8333 respectively]). CONCLUSION: CTTA revealed several parameters with excellent diagnostic performance in differentiating thymoma from thymic hyperplasia and MK/ITMIG high vs low stages. CTTA could potentially serve as a non-invasive tool for this stratification. ADVANCES IN KNOWLEDGE: This study has employed texture analysis, a novel radiomics method on DECT scans to determine the best performing parameter and their corresponding cut-off values to differentiate among the above-mentioned categories. These new parameters may help add another layer of confidence to non-invasively stratify and prognosticate patients accurately which was only previously possible with a biopsy.

WHO classification of soft tissue tumours 2020: An update and simplified approach for radiologists.

The WHO classification of soft tissue tumours categorizes the lesions based on histological differentiation. In the recent fifth edition (2020), many new entities have been introduced, based on their distinct biological behaviour, genetics and morphology. With the recent advances and better understanding of molecular genetics, several novel recurrent genetic alterations have been incorporated in this edition. These may serve as reliable diagnostic and prognostic markers for various soft tissue tumours. Though predominantly a pathologist's game; the radiologists must be aware of the recent updates to contribute towards the optimal diagnosis and management of soft tissue tumours. The imaging features of the new entities have not yet been described but are expected to be explored in the coming years. We hereby present a concise review of the updates in the recent WHO classification of soft tissue tumours. We have tried to emphasize the novel molecular genetics and their surrogate immunohistochemical markers which have brought a paradigm shift in the diagnosis, therapeutics, and prognosis of soft tissue tumours. We also present simplified diagnostic algorithms to characterize soft tissue tumours based on the clinico-radiological features.