NonScarring Diffuse Hair Loss in Women: a Clinico‐Etiological Study from tertiary care center in North‐West India

Journal of Cosmetic Dermatology, EarlyView.

Identification of tumor margins using diffuse reflectance spectroscopy with an extended‐wavelength spectrum in a porcine model

Skin Research and Technology, EarlyView.

Violaceous papules on the hands

Clinical and Experimental Dermatology, EarlyView.

Alkyl glucosides: Newly identified allergens in foam wound dressings

Contact Dermatitis, EarlyView.

Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke: From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (E

Mobile Stroke Unit Reduces Time to Image Acquisition and Reporting [INTERVENTIONAL]

SUMMARY:

Timely administration of thrombolytic therapy is critical to maximizing the likelihood of favorable outcomes in patients with acute ischemic stroke. Although emergency medical service activation overall improves the timeliness of acute stroke treatment, the time from emergency medical service dispatch to hospital arrival unavoidably decreases the timeliness of thrombolytic administration. Our mobile stroke unit, a new-generation ambulance with on-board CT scanning capability, reduces key imaging time metrics and facilitates in-the-field delivery of IV thrombolytic therapy.

Another Important Pitfall in the Diagnosis of Dural Sinus Thrombosis in Neonates [LETTERS]

Radiation-Induced Myelitis: Initial and Follow-Up MRI and Clinical Features in Patients at a Single Tertiary Care Institution during 20 Years [SPINE]

SUMMARY:

Myelitis is a rare complication of radiation exposure to the spinal cord and is often a diagnosis of exclusion. A retrospective review of clinical records and serial imaging was performed to identify subjects with documented myelitis and a history of prior radiation. Eleven patients fulfilled the inclusion criteria. All patients had longitudinally extensive cord involvement with homogeneous precontrast T1 hyperintense signal in the adjacent vertebrae, corresponding to the radiation field. T2 signal abnormalities involving the central two-thirds of the cord were seen in 6/11 patients (55%). The degree of cord expansion and contrast enhancement was variable but was seen in 6 (54%) and 5 (45%) patients, respectively. On follow-up, 2 patients developed cord atrophy, while complete resolution was noted in 1. Clinical improvement was noted in 5 patients, with symptom progression in 2 patients. Our results suggest that radiation myelitis is neither universally progressive nor permanent, and some radiographic and clinical improvement may occur.

Balanced Steady-State Free Precession Sequence (CISS/FIESTA/3D Driven Equilibrium Radiofrequency Reset Pulse) Increases the Diagnostic Yield for Spinal Drop Metastases in Children with Brain Tumors [SPINE]

BACKGROUND AND PURPOSE:

Identification of spinal drop metastases is important in the staging and management of pediatric patients with primary brain tumors. Our aim was to assess the diagnostic utility of the balanced steady-state free precession (bSSFP) sequence (CISS/FIESTA/3D driven equilibrium radiofrequency reset pulse) for the detection of spinal drop metastases in pediatric patients with primary intracranial tumors.

MATERIALS AND METHODS:

This was a retrospective study of 44 pediatric patients with primary intracranial tumors undergoing MR imaging spine evaluation for drop metastases before radiation treatment. All patients underwent a whole-spine MRI with both bSSFP and postcontrast T1WI sequences. Two neuroradiologists independently reviewed only the bSSFP sequence, then 1 week later only the postcontrast T1WI sequence.

RESULTS:

Patients ranged from 1 to 18 years of age (mean, 7.1 ± 4.2 years) with 27 males and 17 females. The number of lesions per patient ranged from 1 to 13 and from 2 to 11 mm in size. Lesions suspicious for drop metastases were seen in 8 patients on the postcontrast T1WI (18%) compared with 10 patients on the bSSFP sequence (23%). Twenty-two drop metastases seen on the bSSFP sequence were not visible on the postcontrast T1WI, including nonenhancing drop metastases and multiple nodules of <3 mm. Interrater agreement was excellent for the bSSFP sequence (0.91) and the postcontrast T1 sequence (0.90).

CONCLUSIONS:

The bSSFP sequence increased the diagnostic yield for the detection of drop metastases in pediatric patients with primary intracranial tumors and was particularly advantageous for small drop metastases (<3 mm) and nonenhancing metastases, and it decreased the number of false-positives. The bSSFP sequence may be an important adjunct to postcontrast T1WI for the evaluation of drop metastases.

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age [PEDIATRICS]

BACKGROUND AND PURPOSE:

Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth.

MATERIALS AND METHODS:

Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7–27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression.

RESULTS:

A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter.

CONCLUSIONS:

Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development.

Neuroimaging Findings of Zika Virus-Associated Neurologic Complications in Adults [REVIEW ARTICLE]

SUMMARY:

When the first suspected cases of neurologic disorders associated with the Zika virus were noticed in Brazil in late 2015, several studies had been conducted to understand the pathophysiology of the disease and its associated complications. In addition to its well-established association with microcephaly in neonates, the Zika virus infection has also been suggested to trigger other severe neurologic complications in adults, such as Guillain-Barré syndrome, radiculomyelitis, and meningoencephalitis. Hence, the Zika virus should be deemed a global threat that can cause devastating neurologic complications among individuals in all age ranges. The aim of this review was to further describe neuroimaging findings of Zika virus infection and associated neurologic complications found in adults.

Rapid-Sequence MRI of the Brain: A Distinct Imaging Study [LETTERS]

Prediction of Borderzone Infarction by CTA in Patients Undergoing Carotid Embolization for Carotid Blowout [EXTRACRANIAL VASCULAR]

BACKGROUND AND PURPOSE:

Permanent common carotid artery and/or ICA occlusion is an effective treatment for carotid blowout syndrome. Besides postoperative thromboembolic infarction, permanent common carotid artery and/or ICA occlusion may cause borderzone infarction when the collateral flow to the deprived brain territory is inadequate. In this study, we aimed to test the predictive value of CTA for post–permanent common carotid artery and/or ICA occlusion borderzone infarction in patients with carotid blowout syndrome.

MATERIALS AND METHODS:

In this retrospective study, we included 31 patients undergoing unilateral permanent common carotid artery and/or ICA occlusion for carotid blowout syndrome between May 2009 and December 2016. The vascular diameter of the circle of Willis was evaluated using preprocedural CTA, and the risk of borderzone infarction was graded as very high risk, high risk, intermediate risk, low risk, and very low risk.

RESULTS:

The performance of readers' consensus on CTA for predicting borderzone infarction was excellent, with an area under receiver operating characteristic curve of 0.938 (95% confidence interval, 0.85–1.00). We defined very high risk, high risk, and intermediate risk as positive for borderzone infarction, the sensitivity, specificity, positive predictive value, and negative predictive value of CTA for borderzone infarction were 100% (7/7), 62.5% (15/24), 43.8% (7/16), and 100% (15/15), respectively. The interobserver reliability was excellent ( = 0.807). No significant difference in the receiver operating characteristic curves was found between the 2 readers (P = .114).

CONCLUSIONS:

CTA can be used to predict borderzone infarction after permanent common carotid artery and/or ICA occlusion by measuring the collateral vessels of the circle of Willis.

European cancer mortality predictions for the year 2018 with focus on colorectal cancer

Abstract

Background

We projected cancer mortality statistics for 2018 for the European Union (EU) and its six more populous countries, using the most recent available data. We focused on colorectal cancer.

Materials and methods

We obtained cancer death certification data from stomach, colorectum, pancreas, lung, breast, uterus, ovary, prostate, bladder, leukaemia, and total cancers from the World Health Organisation database and projected population data from Eurostat. We derived figures for France, Germany, Italy, Poland, Spain, the UK, and the EU in 1970–2012. We predicted death numbers by age group and age-standardized (world population) rates for 2018 through joinpoint regression models.

Results

EU total cancer mortality rates are predicted to decline by 10.3% in men between 2012 and 2018, reaching a predicted rate of 128.9/100 000, and by 5.0% in women with a rate of 83.6. The predicted total number of cancer deaths is 1 382 000 when compared with 1 333 362 in 2012 (+3.6%). We confirmed a further fall in male lung cancer, but an unfavourable trend in females, with a rate of 14.7/100 000 for 2018 (13.9 in 2012, +5.8%) and 94 500 expected deaths, higher than the rate of 13.7 and 92 700 deaths from breast cancer. Colorectal cancer predicted rates are 15.8/100 000 men (−6.7%) and 9.2 in women (−7.5%); declines are expected in all age groups. Pancreatic cancer is stable in men, but in women it rose +2.8% since 2012. Ovarian, uterine and bladder cancer rates are predicted to decline further. In 2018 alone, about 392 300 cancer deaths were avoided compared with peak rates in the late 1980s.

Conclusion

We predicted continuing falls in mortality rates from major cancer sites in the EU and its major countries to 2018. Exceptions are pancreatic cancer and lung cancer in women. Improved treatment and—above age 50 years—organized screening may account for recent favourable colorectal cancer trends.

Taking it in the chin: vitamin K1 for the prevention of acneiform rash

In this issue of Annals of Oncology, Hofheinz et al. study the efficacy of a topical formulation of vitamin K1 in the prevention of a disfiguring toxicity resulting from epidermal growth factor receptor (EGFR) inhibitors [1]. An acneiform rash on the face and upper body develops in the majority of patients treated with EGFR inhibitors [2]. In addition to its psychosocial impact [3], it is associated with symptoms of pruritus and pain, may result in secondary infections [4], all of which may lead to inconsistencies in the dosing of causal anticancer agents [5]. Since the rash has been correlated with antitumor efficacy across most solid tumors in which it has been employed [6], mitigating this untoward event has been the subject of research for the past 15 years.

Targeting cell cycle dependencies represent a novel therapeutic approach for selected sarcoma subgroups

Adult soft tissue sarcoma (STS) represents a group of rare malignant tumours associated with a very poor prognosis in the metastatic setting, with <20% of patients surviving 5 years after diagnosis [1]. Beyond their biological aggressiveness, under-recognition misdiagnosis of STS also contributes to this increased mortality. Management by specialized multidisciplinary boards is recommended and improves patients' survival [2].

ESR1 and endocrine therapy resistance: more than just mutations

Estrogen receptor (ER)-positive breast cancer accounts for 70%–80% of all diagnosed breast cancers [1]. The adoption of endocrine therapies, including ER modulators/degraders (SERMs/SERDs), which antagonize ER, and aromatase inhibitors (AIs), which suppress estrogen synthesis, as the mainstay of treatment of ER-positive breast cancer patients has resulted in substantial survival benefit for patients with early stage disease [2]. Treating ER-positive metastatic breast cancer (MBC), however, remains a significant clinical challenge, due to the development of secondary resistance to all modalities of endocrine therapy [3]. Recently, studies have identified recurrent somatic mutations within the ligand-binding domain (LBD) of ESR1 (encoding ER) in >30% of ER-positive MBC [4–8]. These mutations alter the conformation of ER and produce a constitutively active form of the protein. Mutations at residues 536–538, in particular, promote ER activity in the absence of ligand, resulting in resistance to AIs and reduced sensitivity to SERMs/SERDs [4, 5]. ESR1 fusion genes have also been reported in ER-positive MBCs; however, a detailed description of their manifestations and clinical prevalence is lacking [9]. In this issue of Annals of Oncology, Hartmaier et al. reported the identification of recurrent hyperactive ESR1 fusion genes in breast cancers resistant to endocrine therapy [10], adding to the diversity of reported ESR1 alterations.

Time is up for PD-L1 testing standardization in lung cancer

The treatment options for patients with advanced non-small-cell lung carcinoma have undergone major changes in the recent years, particularly after the FDA approval of PD-1/PD-L1 immune checkpoint inhibitors nivolumab, pembrolizumab and atezolizumab) [1–8]. Each PD-1/PD-L1 inhibitor was approved together with a specific PD-L1 immunohistochemistry assay used in the clinical trials. In addition to unique primary antibody, each assay is optimized for use with a different detection system (i.e. Dako Link 48 and Ventana BenchMark) and a different diagnostic kit. Furthermore, the unique scoring algorithms for immunohistochemical assays were co-developed with each immune checkpoint inhibitor based on predictive values shown in the clinical trials. The one drug–one assay approach is challenging to implement in clinical practice as most laboratories do not use all of the staining platforms and such practice leads to avoidable escalation of laboratory testing cost and health care in general. The main question is whether laboratories will make effort to implement the FDA approved predictive assays for one or more anti-PD-1/PD-L1 checkpoint inhibitors or implement one or more affordable laboratory developed tests (LDTs) using already available testing platforms. To find the answer to this question it is essential to determine analytical concordance between commercially available PD-L1 immunohistochemical assays. Several studies showed an excellent analytical concordance between either FDA approved or LDTs [9–13]. Three assays SP263, 22C3 and 28-8 showed a high concordance in percentage of PD-L1 membrane staining of tumor cells at any intensity. In contrast, lower expression of PD-L1 on tumor cells was observed with SP142 clone. In terms of interpretation, interobserver concordance was high for tumor cell PD-L1 expression, while it was low for immune cells.

Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer

Abstract

Background

There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC.

Patients and methods

In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m² intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS).

Results

A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%).

Conclusions

Vinflunine 280 mg/m² q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m² merits evaluation.

ClinicalTrials.gov

NCT01091168.

Computational prediction of neoantigens: do we need more data or new approaches?

The capability of the immune system for self-recognition has recently become the focus of interest for a broadening research community due to the impressive clinical results achieved with immune checkpoint inhibitors and other immunotherapies in the treatment of advanced metastatic carcinoma [1]. A significant portion of this clinical efficacy is attributed to the fact that the genomic instability of cancer generates mutation-derived peptides (neopeptides) that are not present in normal cells. A subset of these neopeptides may be neoantigens (also called neoepitopes) which are recognized as alien by cytotoxic T cells. Ideally, a cell producing neoantigens should be eliminated by the immune system. However, tumors are able to inhibit this immune response by activating various checkpoint mechanisms; these can be overcome by the now widely used therapeutic agents of checkpoint inhibitors such as anti PD-L1 or anti-CTLA-4 antibodies. There is increasing evidence that such neoantigen-driven immune responses are responsible for the significant clinical response shown to immune checkpoint inhibitors in at least one specific type of tumors, microsatellite instable cancer [2, 3].