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Adrenoleukodystrophy (ALD) is an X linked recessive genetic disorder caused by an abnormality in the ABCD1 gene on the X chromosome, that affects 1 in 20 000 people. In X linked adrenoleukodystrophy (X-ALD), a defect in lignoceroyl-coenzyme A ligase causes pathognomonic tissue accumulation of very long chain fatty acids (VLCFA) in the adrenal cortex and nervous system. The phenotypic variability ranges from cerebral inflammatory demyelination of childhood onset, leading to death within 5 years, to adults remaining presymptomatic through more than five decades. Our case is that of a man who was previously diagnosed with bipolar affective disorder presented with dystonic posturing. During transit, he had an episode of generalised convulsive status epilepticus. He presented with spasticity and exaggerated reflexes. Three important signs of adrenal insufficiency were observed: hypotension, hyperpigmentation and comatose state. The diagnosis of X-ALD should be considered in young men presenting with gradually progressive unexplained cognitive and behavioural problems, a strong family history, adrenal insufficiency, bilateral upper motor signs with absent ankle reflexes.

Maxillomandibular or dental arcade arteriovenous malformations (AVMs) are uncommon lesions with potential for life-threatening bleeding. We report three cases of vascular malformations and a case of pyogenic granuloma and propose a contrast-enhanced computed tomography (CT)-based workup of these lesions for definitive treatment. Four cases of orodental bleeding were diagnosed based on CT angiography (CTA) and treated using endovascular means. Three of them were subsequently operated and confirmed by histopathology. Two were low-flow AVMs, the third one a case of pyogenic granuloma, and one high-flow AVM. The first three lesions were embolized with polyvinyl alcohol particles and subsequently operated and the fourth high-flow one embolized using liquid embolic agent n-butyl cyanoacrylate (Glue). CTA can be used to show separate lesions of arterial vascularity and those of delayed/ venous enhancing lesions. Arterial phase-enhancing lesions are again subdivided in digital subtraction angiography into those of low-to-moderate vascularity and those with high flow, which are treated using particle embolization and liquid glue/onyx (± coil) embolization, respectively. The delayed venous phase enhancing lesions may mimic neoplasms and after tissue biopsy may be managed by sclerotherapy.

Dorsal arachnoidal webs are condensations of arachnoidal tissue densely adherent to the pial surface of the posterior aspect of the dorsal spinal cord. Infrequently described in literature they disrupt the flow of CSF in the spinal subarachnoid space leading to syringomyelia and myelopathy. While there are several theories on their origin, the “scalpel sign” on magnetic resonance imaging is considered to be pathognomonic of this condition. An illustrative case of a 58 year old man with syringomyelia and dorsal cord indentation who presented with spastic paraparesis, gait instability, parasthesias and bilateral non radicular upper limb pain that resolved following excision of the web is described to highlight the importance of considering this diagnosis when cases of so called “idiopathic” syringomyelia are encountered.

Peroxisome proliferator-activated receptors (PPARs) activity has significant implications for the development of novel therapeutic modalities against neurodegenerative diseases. Although PPAR-α, PPAR-β/δ, and PPAR-γ nuclear receptor expressions are significantly reported in the brain, their implications in brain physiology and other neurodegenerative diseases still require extensive studies. PPAR signaling can modulate various cell signaling mechanisms involved in the cells contributing to on- and off-target actions selectively to promote therapeutic effects as well as the adverse effects of PPAR ligands. Both natural and synthetic ligands for the PPARα, PPARγ, and PPARβ/δ have been reported. PPARα (WY 14.643) and PPARγ agonists can confer neuroprotection by modulating mitochondrial dynamics through the redox system. The pharmacological effect of these agonists may deliver effective clinical responses by protecting vulnerable neurons from Aβ toxicity in Alzheimer’s disease (AD) patients. Therefore, the current review delineated the ligands’ interaction with 3D-PPARs to modulate neuroprotection, and also deciphered the efficacy of numerous drugs, viz. Aβ aggregation inhibitors, vaccines, and γ -secretase inhibitors against AD; this review elucidated the role of PPAR and their receptor isoforms in neural systems, and neurodegeneration in human beings. Further, we have substantially discussed the efficacy of PPREs as potent transcription factors in the brain, and the role of PPAR agonists in neurotransmission, PPAR gamma coactivator-1α (PGC-1α) and mitochondrial dynamics in neuroprotection during AD conditions. This review concludes with the statement that the development of novel PPARs agonists may benefit patients with neurodegeneration, mainly AD patients, which may help mitigate the pathophysiology of dementia, subsequently improving overall the patient’s quality of life.

BACKGROUND: Improved understanding of the pathways associated with airway pathophysiologic features in COPD will identify new predictive biomarkers and novel therapeutic targets. RESEARCH QUESTION: Which physiologic pathways are altered in the airways of patients with COPD and will predict exacerbations? STUDY DESIGN AND METHODS: We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the multicenter Subpopulations and Intermediate Outcome Measures in COPD Study. Biomarkers elevated in sputa from patients with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations. RESULTS: Sputum supernatants from 980 patients were analyzed: 77 healthy nonsmokers, 341 smokers with preserved spirometry, and 562 patients with COPD (178 with Global Initiative on Chronic Obstructive Lung Disease [GOLD] stage 1 disease, 303 with GOLD stage 2 disease, and 81 with GOLD stage 3 disease) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (false discovery rate, 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were associated strongly with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations. INTERPRETATION: Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiologic characteristics. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum-soluble phase biomarkers improves prediction of pulmonary exacerbations. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01969344; URL: www.clinicaltrials.gov

Background/Purpose As survival rates for patients with congenital diaphragmatic hernia (CDH) increase, long-term sequelae become increasingly prevalent. We present the outcomes of patients who underwent CDH repair at our institution and discuss standardization of follow-up care in our long-term multidisciplinary follow-up clinic. Methods A retrospective review of patients followed in multidisciplinary clinic after CDH repair at our institution from January 1, 2005 to December 1, 2020. Results A total of 193 patients met inclusion criteria, 73 females (37.8%) and 120 males (62.2%). Left-sided defects were most common (75.7%), followed by right-sided defects (20.7%). Median age at repair was 4 days (IQR 3–6) and 59.6% of all defects required patch repair. Median length of stay was 29 days (IQR 16.8–50.0). Median length of follow up was 49 months (IQR 17.8–95.3) with 25 patients followed for more than 12 years. Long-term outcomes included gastroesophageal reflux disease (42.0%), diaphragmatic hernia recurrence (10.9%), asthma (23.6%), neurodevelopmental delay (28.6%), attention deficit hyperactivity disorder (7.3%), autism (1.6%), chest wall deformity (15.5%), scoliosis (11.4%), and inguinal hernia (6.7%). Conclusion As survival of patients with CDH improves, long-term care must be continuously studied and fine-tuned to ensure appropriate surveillance and optimization of long-term outcomes.

This review and meta-analysis aims to assess the prognostic value of the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score for detecting necrotizing fasciitis in the extremities. The LRINEC score has been validated in multiple studies as a clinical tool for differentiating necrotizing fasciitis from non-necrotizing infections however many studies do not specify the location of infection. As the prevalence of diabetes and diabetic foot infections continues to rise, the utility of LRINEC scores in these populations becomes of increased importance. Four databases were reviewed for citations between January 2010 and December 2020. English, full text articles reporting the diagnostic effects of LRINEC were utilized in the systematic review portion of this paper. Further inclusion of 2 × 2 tables and discussion specific to the extremities were applied for citations implemented in the meta-analysis. Of the 111 results, 12 citations (n = 932) were included in this review. The diagnostic sensitivity of the LRINEC score ranged from 36% to 77% while specificity ranged from 72% to 93%. Cumulative odds ratio for LRINEC ≥6 among the 4 studies assessing extremity necrotizing fasciitis was 4.3 with p value of

RATIONALE: Whether biomarkers can be used to predict response to inhaled corticosteroids (ICS) or long-acting muscarinic antagonists (LAMA) in mild persistent asthma is unclear. OBJECTIVES: In a prespecified exploratory analysis of a randomized clinical trial of 295 participants 12 years of age or older with uncontrolled mild persistent asthma, we sought to identify biomarkers of treatment response after 12 weeks of ICS (mometasone, 200 μg or 220 μg twice/d), LAMA (tiotropium, 5 μg/d), or placebo in adults (⩾18 yr) and adolescents (12–17 yr) separately. METHODS: The primary outcome was a composite outcome of asthma control (treatment failure, asthma control days, and forced expiratory volume in 1 second [FEV(1)]). Analyses examined type 2 inflammatory biomarkers and physiologic biomarkers. We assessed the area under the receiver operating characteristic curve (AUC) for response to ICS and LAMA (each versus placebo). An AUC of 0.5 suggests no discrimination, 0.7–0.8 is considered acceptable, more than 0.8–0.9 is considered excellent, and more than 0.9 is considered outstanding. RESULTS: In 237 adults, sputum and blood eosinophil levels and fractional exhaled nitric oxide (Fe(NO)) each predicted ICS response (AUCs: 0.61 [95% confidence interval (CI), 0.53–0.69], 0.64 [95% CI, 0.56–0.72], and 0.62 [95% CI, 0.54–0.70], respectively; all P

Liver tumours are uncommon in the paediatric population, constituting 1–2 % of all paediatric tumours and 4% of all paediatric liver tumours. Hepatoblastoma followed by hepatocellular carcinoma is the most common tumours in this age group. Simultaneous development of two discrete liver tumours of distinct histologies (collision tumour) has been occasionally reported in adults but never in children. We hereby present the first reported case of hepatic collision tumours (hepatocellular carcinoma and cholangiocarcinoma) in the explant liver of a child who underwent living donor liver transplantation for end-stage liver disease and severe hepatopulmonary syndrome. The manuscript describes the clinical, radiological and histopathological findings of this case and also highlights the dilemma associated with management of this case had the diagnosis been made in the preoperative setting and also about the proposed management plan for this case in the postoperative period.

Summary Objective This systematic review and meta-analysis aimed to define the current evidence and systematically summarize the relevant data regarding the utility and safety of hyperbaric oxygen therapy (HBOT) as an adjunctive treatment in complicated re-operative cases of hypospadias. Method The authors systematically searched the PubMed, EMBASE, Web of Science, and Scopus databases on August 5, 2021. Patients were divided into two groups, i.e. HBOT and non-HBOT. The main outcomes were graft failure rate and the incidence of complications following urethroplasty. The proportion of patients developing adverse events due to HBOT was the secondary outcome. The pooled risk ratio and heterogeneity were calculated using the Mantel-Haenszel method and the I2 statistics respectively. The quality assessment of the included studies was performed using the Downs and Black scale. Result Four studies constituting 176 patients (101 in the HBOT group) were included (Figure). Variations were observed among these studies in terms of the age of participants, the number and types of previous operations performed, and the protocol of administration of HBOT. The graft failure rate (RR 0.19; 95% CI 0.05–0.73, p = 0.02) and the incidence of complications (RR 0.40, 95% CI 0.20–0.77, p = 0.007) were significantly low in the HBOT versus the non-HBOT group. Apart from myringotomy insertion (n = 10; 9.9%) and claustrophobia (n = 1), no other adverse events were associated with HBOT. All studies had a moderate risk of bias. An almost perfect agreement (kappa = 0.956, p Conclusion The present systematic review and meta-analysis significantly favor the administration of HBOT versus no HBOT in terms of graft failure rate and incidence of complications following urethroplasty. The available data also highlights the safety of HBOT in complicated cases of hypospadias. However, well-designed randomized controlled trials need to be conducted for an optimal comparison between the two treatment groups.

Rationale: Individuals with Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. Objectives:...

This study quantifies the performance of an international cohort of cornea specialists in image-based differentiation of bacterial and fungal keratitis, identifying significant regional variation and establishing a reference standard for comparison against machine learning models.

Superior mesenteric arteriovenous fistula is an extremely rare vascular malformation with most cases occurring following abdominal trauma or surgery. They are often asymptomatic or present with various abdominal symptoms with or without features of portal hypertension. A 30-year-old man developed fistulising of the superior mesenteric artery into the superior mesenteric vein following bowel resection surgery for an acquired midgut volvulus. Although endovascular management remains the treatment of choice in such cases due to increased morbidity of a repeat abdominal surgery, definite risks remain, such as coil migration, which happened in this case. The open surgical approach remains the only option in such instances.

Pediatric pulmonary hypertension (PH) is a rare disease with historically very high morbidity and mortality. In the past 20 years, there has been a growing recognition that pediatric PH, although having similarities to adult PH, is a unique entity with its own particular pathogeneses, presentation, and management. With better understanding and earlier diagnosis of pediatric PH, and as more medications have become available, survival of children with PH has also significantly improved. This article reviews the various forms of PH in childhood, with a focus on both established and investigational therapies that are available for children with PH.

Early identification and diagnosis of brain tumor using a supervised approach plays an essential role in the field of medicine. In this paper, an automated computer-aided method using deep learning architecture named CNN Deep net is proposed for the detection, classification and diagnosis of meningioma brain tumor. This proposed method includes preprocessing, classification, and segmentation of the primary occurring brain tumor in adults. The proposed CNN Deep Net architecture extracts the features internally from enhanced image and classifies them into normal and abnormal tumor images. The segmentation of tumor region is performed by the global thresholding with area morphological function method. This proposed method of fully automated classification and segmentation of brain tumor preserves the spatial invariance and inheritance. Furthermore, based on its feature attributes the proposed CNN Deep net classifier, classifies the detected tumor image belongs either to (low grade)benign or (high grade)malignant. This proposed CNN Deep net classification methodology approach with grading system is evaluated both quantitatively and qualitatively. The quantitative measures such as sensitivity, specificity, accuracy, Dice similarity coefficient, precision, F-score of the proposed classification and segmentation methodology states a better segmentation accuracy and classification rate of 99.4% and 99.5% with respect to ground truth images.

Background and aims Recent evidence links trimethylamine oxide (TMAO) to endothelial dysfunction, an early indicator of cardiovascular disease. We aimed to determine whether short-term consumption of a diet patterned after the 2010 Dietary Guidelines for Americans (DGA) would affect endothelial function, plasma TMAO concentrations, and cardiovascular disease risk, differently than a typical American Diet (TAD). Methods and results An 8-wk controlled feeding trial was conducted in overweight/obese women pre-screened for insulin resistance and/or dyslipidemia. Women were randomized to a DGA or TAD group (n = 22/group). At wk0 (pre-intervention) and wk8 (post-intervention) vascular age was calculated; endothelial function (reactive hyperemia index (RHI)) and augmentation index (AI@75) were measured using EndoPAT, and plasma TMAO was measured by LC-MS/MS. Vascular age was reduced in DGA at wk8 compared to wk0 but TAD wk8 was not different from wk0 (DGA wk0: 54.2 ± 4.0 vs. wk8: 50.5 ± 3.1 (p = 0.05), vs. TAD wk8: 47.7 ± 2.3). Plasma TMAO concentrations, RHI, and AI@75 were not different between groups or weeks. Conclusion Consumption of a diet based on the 2010 Dietary Guidelines for Americans for 8 weeks did not improve endothelial function or reduce plasma TMAO. ClinicalTrials.gov NCT02298725.

Sinus of Valsalva (SOV) fistulas are rare entities and have been infrequently described after episodes of aortic valve (AV) infective endocarditis (IE). Patients with SOV fistulas or ruptured SOV aneurysms can present with varying symptoms and physical exams. Identification of SOV fistulas is crucial, with frequent need for surgical intervention due to risk of congestive heart failure or cardiogenic shock. We present a case of a SOV-to-right atrial (RA) fistula from AV IE that was diagnosed by intraoperative transesophageal echocardiography (TEE). Management included AV replacement (AVR) and aortic root debridement, tricuspid valve annular debridement and annuloplasty, and closure of the fistula tract using a pericardial patch.

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene–environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: “young” individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider “young” patients with COPD those patients in the age range of 20–50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age.

BACKGROUND Cytopenia is the most common condition in paediatric population which requires detailed haematological evaluation. The objective of this study was to understand the, aetiological factors of the three types of cytopenia (single cytopenia, bicytopenia, pancytopenia) in children. METHODS This study is a descriptive & retrospective 5 year study conducted in the Haematology wing of a paediatric tertiary health care centre in South India. Data of all cases who underwent detailed haematological evaluation like Complete blood count, peripheral smear and bone marrow examination for cytopenias during the study period were included in the study. RESULTS The study sample was 365. The total number of patients with single cytopenia (isolated anaemia / leukopenia / thrombocytopenia) was 240 (65.7 %), bicytopenia were 90 (24.6 %) and pancytopenia was 35 (9.58 %). There was slight female predominance (M: F = 1: 1.05). Bicytopenia and pancytopenia were commonly observed between 1 - 5 years of age, while single cytopenias were more common in 5 - 10-year age group. The analysis of symptoms and signs in all cytopenia groups showed petechiae / purpura as the most common presentation in single cytopenia. The analysis of clinical symptoms showed significant correlation (P value < 0.05). Single cytopenia was the most common observed type of cytopenia with Immune thrombocytopenic purpura as the commonest aetiologic factor. In the present study most common causes of bicytopenia were reactive conditions like ITP with and without anaemia, infections etc. Acute Lymphoblastic Leukaemia (ALL) was the most common aetiologic factor for pancytopenia (ANOVA test and Bonferroni test P value < 0.05). Isolated thrombocytopenia was the most common peripheral smear picture observed, followed by hypochromic microcytic picture and combination of hypochromic microcytic anaemia (HMA) with thrombocytopenia. CONCLUSIONS Children with cytopenias commonly have benign conditions than malignant conditions. Cytopenias due to primary haematological malignancies are more common than secondaries. KEYWORDS Bicytopenia, Cytopenia, Children, Aetiology, Paediatric Pancytopenia

Aims: This work was focused on the detection of early-stage breast tumors and their location. Background: The most frequently seen disease progression and mortality in women's lives is Breast Cancer. Because of breast cancer/tumors, the risk of mortality for women has risen exponentially. From the 2020 deadline for breast cancer, women who died from carcinoma were 123.8 cases per lac women between 2006-2010. This problem is also overcome by the early identification of the tumor using different detection procedures like X-ray mammography, computerized tomography, ultrasound imaging technique, Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI), microwave imaging. Researchers carried out multiple studies in these areas. Objective: To detect early-stage breast tumors and their location using SAR analysis. Methods: The major dielectrical difference between cancerous breast tissues and normal tissues in this technique is the microwave frequency range. The term Specific Absorption Rate (SAR) describes the amount of energy which is absorbed (W/kg) in the breast tissue. This segment illustrates the usefulness to diagnose the tumor position in the breast by means of maximum SAR value coordinates. Changes in breast and tumor size are important for the risk of diagnosis. The power absorbed in connecting with a normal breast and a tumor breast is measured and equivalent for different breast masses. The maximum SAR is also analyzed at distinct tumor locations at various frequency ranges. Results: It is observed that max SAR coordinates are very close to the actual tumor location. So, the maximal value of SAR coordinates indicates the existence of a tumor in the breast phantom. Conclusion: The simulated data above strongly suggests that the Max SAR values were higher in the breast phantom with tumor as compared to the breast without tumor. With different tumor radius (3 mm and 5 mm) analyzed with different resonant frequencies like 3GHz, 4GHz and 5GHz at the actual tumor location of (0, 0, 35). Even though a model representing the real properties of breast tissue is required to assess the validation of any imaging process, so the real-time development of an equivalent breast phantom and its execution is needed.

Purpose of review Many healthcare systems rapidly implemented telehealth as a substitute for in-person care during the coronavirus disease 2019 (COVID-19) pandemic. The purpose of this review is to describe the evidence base supporting the use of telehealth for chronic obstructive pulmonary disease (COPD) prior to the COVID-19 pandemic, discuss the barriers to implementing telehealth during the pandemic, and share our opinion about the future of telehealth in COPD. Recent findings The evidence from randomized clinical trials in COPD completed prior to the COVID-19 pandemic indicate that the effectiveness of telehealth interventions compared to in-person usual care on clinical outcomes is inconclusive. Recent experience during the COVID-19 pandemic indicates that telehealth may increase access to healthcare and satisfaction with care when delivered in addition to usual in-person care. While some reimbursement-related barriers to telehealth have been alleviated during the COVID-19 pandemic, several patient, provider, and health-system barriers to implementation remain. Summary There is a need to further evaluate the delivery of telehealth services as an adjunct to traditional in-person models of COPD care. Standardization and reporting of core clinical, satisfaction, accessibility, and quality of care outcomes are needed to promote cross-study learning and more rapid translation of research evidence into practice.

Objective Decision-making in chronic pain patients involves a combination of subjective and objective criteria, including patient history, physical examination, imaging, and patient response to prior treatments, clinical experience, probabilities, and recognition of patterns. However, there is a distinct lack of objective laboratory biomarkers in use in routine clinical care. The objective was to review the literature to identify and describe specific biomarkers in chronic pain management. Methods This is a narrative review of the literature regarding the use of laboratory biomarkers in chronic pain. A librarian-assisted literature search of the PubMed, Science Direct, and Google Scholar databases was performed and resulted in 304 possible manuscripts. We included manuscripts assessing laboratory collected biomarkers from urine, serum, cerebrospinal fluid, and saliva. After screening and review of the initial literature search results, a total of 75 manuscripts were included in the narrative review. Conclusion The studies reviewed suggested that specific biomarkers may help identify those patients at risk of disease development and function as a prognostic indicator for disease progression and treatment response. However, additional research is necessary before specific recommendations can be made, and current clinical decision-making is modified.

Please see the Editorial Comment by Candice Bolan discussing this article. The treatment of rectal cancer centers around the distinct but related goals of management of distant metastases and manag...

Radiation therapy is a major treatment modality used in > 60% of cancer patients as definitive local treatment for inoperable locoregionally confined tumors and as palliative therapy. Although cytotoxic chemotherapy enhances the effectiveness of treatment, the benefit over radiation therapy alone is modest. There is a need to enhance the effectiveness of local tumor control over what sequentially or concurrently administered cytotoxic chemotherapy provides. Although many biological pathways are known to enhance the effectiveness of radiation therapy, there is currently a paucity of drugs approved for use in combination. Several clinical trials have tested the effectiveness of combining targeted agents or immunotherapies with radiation therapy, but the results of these trials have been negative, likely stemming from the relative lack of preclinical evidence using appropriate experimental standardization or model systems. Accelerating the identification of agents tested in an appropriate clinical context and experimental systems or models would greatly enhance the potential to bring forward early testing of drugs that would not only be safe but also more effective. This article provides an overview of the opportunities and challenges of developing therapeutics to combine with radiation therapy, and some guidance toward preclinical and early clinical testing to improve the chance that advanced phase testing of drug-radiation combinations would be successful in the long term.

The nervous necrosis virus (NNV) infection is generally observed in aquafarms when the seawater temperature is higher than 24 °C and the fishes seem to be refractory to disease at suboptimal temperatures below 20 °C suggesting a role of thermoregulation in NNV pathogenesis. The present study profiled the temperature-dependent regulation of cytokines (TNF-α, IL-1β and IFN-γ), innate antiviral factors (IFN-1, Mx, ISG-15), adaptive immune factors (CD-4, CD-8, IgM), signaling regulators (SOCS-1, SOCS-3), transcription factors (STAT-1, STAT-3) and microglial and NCC/NK specific cell markers (TMEM-119 and NCCRP-1) during NNV challenge in seven-band grouper, Hyporthodus septemfasciatus. The co-habitation challenge at 17 °C with showed a sustained expression of proinflammatory cytokines and following rechallenge with a dose of 104 TCID50/100μL/fish at optimal temperature, the survivors also exhibited a stable expression of immune factors. The 100% survival following the challenge at sub-optimal (17 °C) and rechallenge at optimal (25 °C) was due to the stable and sustained activation of the immune response. However, at 25 °C, the rechallenge displayed a priming effect with hyperactivation of the immune system evident from the immune gene expression profile. The mortality pattern observed is co-related with the cytokine storm as is evident from the gene expression profile. Whereas, neither of the adaptive immune markers was suggestive of humoral immune response in the 17 °C groups. Also, the data suggest a possible role of NK cell and microglia in mediating antiviral immune response following infection in the brain at different temperatures, where, former is beneficial in restricting viral infection with higher host tolerance.

Objectives The aim of this study was to evaluate the efficacy of radiofrequency (RF) energy applications targeting the atrial side of a significant residual leak in patients with acute and chronic evidence of incomplete percutaneous left atrial appendage (LAA) occlusion. Background RF applications have been proved to prevent recanalization of intracranial aneurysms after coil embolization, thereby favoring complete sealing. From a mechanistic standpoint, in vitro and in vivo experiments have demonstrated that RF promotes collagen deposition and tissue retraction. Methods Forty-three patients (mean age 75 ± 7 years mean CHA2DS2-VASc score 4.6 ± 1.4, mean HAS-BLED score 4.0 ± 1.1) with residual leaks ≥4 mm after Watchman implantation were enrolled. Procedural success was defined as complete LAA occlusion or presence of a mild or minimal (1- to 2-mm) peridevice leak on follow-up transesophageal echocardiography (TEE), which was performed approximately 45 days after the procedure. Results RF-based leak closure was performed acutely after Watchman implantation in 19 patients (44.2%) or scheduled after evidence of significant leaks on follow-up TEE in 24 others (55.8%). The median leak size was 5 mm (range: 4-7 mm). On average, 18 ± 7 RF applications per patient (mean maximum contact force 16 ± 3 g, mean power 44 ± 2 W, mean RF time 5.1 ± 2.5 minutes) were performed targeting the atrial edge of the leak. Post-RF median leak size was 0 mm (range: 0-1 mm). A very low rate (2.3% [n = 1]) of major periprocedural complications was observed. Follow-up TEE revealed complete LAA sealing in 23 patients (53.5%) and negligible residual leaks in 15 (34.9%). Conclusions RF applications targeting the atrial edge of a significant peri-Watchman leak may promote LAA sealing via tissue remodeling, without increasing complications. (RF Applications for Residual LAA Leaks [REACT]; NCT04726943 )

Applications of biomaterials in cancer therapy has been limited to drug delivery systems and markers in radiation therapy. In this article, we introduce the concept of phase-functionalization of silicon to preferentially select cancer cell populations for survival in a catalyst and additive free approach. Silicon is phase-functionalized by the interaction of ultrafast laser pulses, resulting in the formation of rare phases of SiO2 in conjunction with differing silicon crystal lattices. The degree of phase-functionalization is programmed to dictate the degree of repulsion of cancer cells. Unstable phases of silicon oxides are synthesized during phase-functionalization and remain stable at ambient conditions. This change in phase of silicon as well as formation of oxides contributes to changes in surface chemistry as well as surface energy. These material properties elicit in precise control of migration, cytoskeleton shape, direction and population. To the best of our knowledge, phase-functionalized silicon without any changes in topology or additive layers and its applications in cancer therapy has not been reported before. This unique programmable phase-functionalized silicon has the potential to change current trends in cancer research and generate focus on biomaterials as cancer repelling or potentially cancer killing surfaces.

Disruption of the blood-brain barrier and occurrence of coagulopathy after traumatic brain injury (TBI) have important implications for multiple secondary injury processes. Given the extent of post-traumatic changes in neuronal function, significant alterations in some targets, such thrombin (a protease that plays a physiological role in maintaining blood coagulation), play an important role in TBI-induced pathophysiology. Despite the magnitude of thrombin in synaptic plasticity being concentration-dependent, the mechanisms underlying TBI have not been fully elucidated. The understanding of this post-injury neurovascular dysregulation is essential to establish scientific-based rehabilitative strategies. One of these strategies may be supporting physical exercise, considering its relevance in reducing damage after a TBI. However, there are caveats to consider when interpreting the effect of physical exercise on neurovascular dysregulation after TBI. To complete this picture, this review will describe how the interactions established between blood-borne factors (such as thrombin) and physical exercise alter the TBI pathophysiology.

Widespread adoption of next-generation techniques such as RNA-sequencing (RNA-seq) has enabled research examining the transcriptome of anucleate blood platelets in health and disease, thus revealing a rich platelet transcriptomic signature that is reprogrammed in response to disease. Platelet signatures not only capture information from parent megakaryocytes and progenitor hematopoietic stem cells but also the bone marrow microenvironment, and underlying disease states. In cancer, the substantive body of research in patients with solid tumours has identified distinct signatures in 'tumour-educated platelets', reflecting influences of the tumour, stroma and vasculature on splicing, sequestration of tumour-derived RNAs, and potentially cytokine and microvesicle influences on megakaryocytes. More recently, platelet RNA expression has emerged as a highly sensitive approach to profiling chronic progressive haematologic malignancies, where the combination of large data cohorts and machine-learning algorithms enables precise feature selection and potential prognostication. Despite these advances, however, our ability to translate platelet transcriptomics toward clinical diagnostic and prognostic efforts remains limited. In this Perspective, we present a few actionable steps for our basic, translational and clinical research communities in advancing the utility of the platelet transcriptome as a highly sensitive biomarker in cancer and collectively enable efforts toward clinical translation and patient benefit.

Ibrutinib is a Bruton tyrosine kinase inhibitor used to treat many hematologic conditions, most commonly B-cell lymphomas and leukemias. Reportedly, skin rash is an adverse event in up to 27% of treated patients. Histopathologic description of these lesions is limited. We present two cases of ibrutinib-associated skin toxicities showing diverse histopathologic features. Case 1: A 72-year-old man was started on ibrutinib for chronic lymphocytic leukemia. Two months later, he developed multiple erythematous crusted papules on the chest, abdomen, and extremities. Biopsies revealed varied histopathology including poorly formed granulomatous dermatitis, epidermal necrosis, ulceration, and panniculitis. Ibrutinib was discontinued and his skin lesions resolved within 1 month. Case 2: A 48-year-old man received ibrutinib after failing standard therapy for primary central nervous system EBV positive diffuse large B-cell lymphoma. Two months after initiation of ibrutinib, he developed multiple firm, red, non-tender nodules on the forehead, buttock, and thigh. Biopsies revealed "pseudolymphoma"-like reaction with dense pandermal lymphohistiocytic inflammation and granulomas. His skin toxicity resolved without cessation of therapy. Awareness of the spectrum of histopathologic features that may be encountered in skin lesions of patients treated with ibrutinib, as illustrated by these two cases, will be critical for optimal patient management.

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home. Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia. Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part. Patients were randomized (2:1) to subcutaneous ofatumumab 20 mg or placebo. Primary outcome was the number of gadolinium-enhancing (Gd+) T1 lesions per scan over 24 weeks. Results: Sixty-four patients were randomized (ofatumumab, n = 43; placebo, n = 21). Primary endpoint was met; ofatumumab reduced Gd + T1 lesions versus placebo by 93.6% ( p < 0.001) and the results were consistent across regions (Japan/Russia). Ofatumumab reduced annualized T2 lesion and relapse rate versus placebo by week 24. Both groups showed benefit from ofatumumab in the extension-part. Incidence of adverse events was lower with ofatumumab versus placebo (69.8% vs 81.0%); injection-related reactions were most common. No deaths, opportunistic infections, or malignancies were reported. Conclusion: Ofatumumab demonstrated superior efficacy versus placebo, with sustained effect through 48 weeks in RMS patients from Japan/Russia. Switching to ofatumumab after 24 weeks led to rapid radiological and clinical benefits. Safety findings were consistent with pivotal trials.

It is quite alarming that the increase of glaucoma is due to the lack of awareness of the disease and the cost for glaucoma screening. The primary eye care centers need to include a comprehensive glaucoma screening and include machine learning models to elaborate it as decision support system. The proposed system considers the state of art of eye gaze features to understand cognitive processing, direction and restriction of visual field. There is no significant difference in global and local ratio and skewness value of fixation duration and saccade amplitude, which suggest that there is no difference in cognitive processing. The significance value of saccadic extent along vertical axis, Horizontal Vertical ratio (HV ratio), convex hull area and saccadic direction show that there is restriction in vertical visual field. The statistical measures (p

Multiple randomized clinical trials have supported the use of mechanical thrombectomy (MT) as standard of care in the treatment of large vessel occlusion acute ischemic stroke. Optimal outcomes depend not only on early reperfusion therapy but also on post thrombectomy care. Early recognition of post MT complications including reperfusion hemorrhage, cerebral edema and large space occupying infarcts, and access site complications can guide early initiation of lifesaving therapies that can improve neurologic outcomes. Knowledge of common complications and their management is essential for stroke neurologists and critical care providers to ensure optimal outcomes. We present a review of the available literature evaluating the common complications in patients undergoing MT with emphasis on early recognition and management.

Background Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC. Methods This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA. Results NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples. Conclusions Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management.

Background Reverse total shoulder arthroplasty (RTSA) has become an increasingly popular surgery for patients with rotator cuff arthropathy, unreconstructible proximal humeral fracture, and end-stage glenohumeral arthritis. The increased annual volume of RTSAs has resulted in more postoperative complications and revision rates between 3.3% and 10.1%. Postoperative infection is one of the most common complications requiring revision surgery after primary RTSA. This study assesses patient-specific risk factors for development of early infection after primary RTSA in a single high-volume shoulder arthroplasty institution. Methods From 2014 to 2019, 902 consecutive primary RTSAs were performed for surgical treatment of rotator cuff arthropathy, glenohumeral arthritis, inflammatory arthropathy, and/or dislocation. Excluding proximal humeral or scapula fractures, 756 cases met the inclusion criteria and had a minimum of 3-month follow-up. All surgeries were performed using the same surgical technique and received similar antibiotic prophylaxis. Age, patient demographics, medical history, smoking history, and prior ipsilateral shoulder treatment and/or surgery were recorded. Multivariable logistic regression analysis was used to determine risk factors associated with development of postoperative shoulder infection. Results Thirty-five patients did not meet minimum follow-up criteria and were lost to follow-up. Overall, of 721, 22 patients (3%) developed a postoperative ipsilateral shoulder infection. Previous nonarthroplasty surgery and history of rheumatoid arthritis were significantly associated with the development of postoperative shoulder infection. Amongst 196 patients who had previous nonarthroplasty shoulder surgery, there were 12 postoperative shoulder infections (6%) compared with those without previous shoulder surgery (10 of 525, 2%) (P = .003). Among 58 patients with rheumatoid arthritis, there were 5 postoperative shoulder infections (9%) compared with patients without rheumatoid arthritis (17 of 663, 3%) (P = .010). Patient age, gender, smoking status, history of diabetes mellitus, history of cancer/immunosuppression, and prior cortisone injection did not demonstrate significant associations with the development of postoperative infection. Conclusion Prior nonarthroplasty shoulder surgery and/or rheumatoid arthritis are independently associated with the development of postoperative infection after primary RTSA. Patients who demonstrate these risk factors should be appropriately evaluated and preoperatively counseled before undergoing primary RTSA. Strong consideration should be given to avoid minimally invasive nonarthroplasty surgery as a temporizing measure to delay definitive RTSA.

Rationale: Diagnosis of chronic obstructive pulmonary disease (COPD) relies on abnormal spirometry. However, spirometry may underestimate the effects of smoking, missing smokers with respiratory di...

Objectives To analyse the pattern of cardiovascular diseases (CVDs) in COVID-19 patients admitted to tertiary cardiac care centre. Methods We retrospectively analysed 511 adult patients admitted between July 1, 2020, and November 30, 2020, with COVID-19 infection and having either new onset or pre-existing CVDs. Clinical features, electrocardiogram (ECG), echocardiography, chest X-ray, biomarkers, haematological and biochemical parameters were analysed. Results The mean age of the patients was 56.62 ± 14.74 years. Male: Female ratio was 2.78:1. Pre-existing CVDs were present in 258 patients (50.5%). The most common cardiovascular manifestation was acute coronary syndrome (ACS), seen in 259 patients (50.7%). ST-segment elevation myocardial infarction (STEMI) was more common than non-ST-segment elevation ACS (NSTE-ACS). Possible myocarditis was seen in 52 patients (10.1%). Rhythm and conduction abnormalities were noted in 144 patients (28.2%), the most common being QT prolongation, seen in 51 patients (10%). In-hospital mortality occurred in 97 patients (18.9%). Age, serum Ferritin level, D-dimer, NT-pro-BNP and total leukocyte count were significantly higher among patients with in-hospital mortality compared to survival group. Blood lymphocyte count and Haemoglobin level were significantly lower in mortality-group, compared to survival-group. Incidence of pre-existing CVDs, cardiogenic shock, heart failure, atrial fibrillation (AF), and renal failure were significantly higher in mortality-group compared to survival-group. Conclusion The most common CVD in COVID-19 patients in our study was ACS. STEMI was more common than NSTE-ACS. Advanced age, elevated serum ferritin, D-dimer, NT pro-BNP, leucocytosis, lymphopenia, lower haemoglobin, pre-existing CVDs heart failure, cardiogenic shock, AF and renal failure were associated with increased mortality in these patients.

Leiomyosarcoma of the inferior vena cava (IVC-LMS) is a rare mesenchymal tumor arising from the tunica media. In this report, we describe the antesitum resection without inferior vena cava (IVC) reconstruction of retrohepatic IVC-LMS. To our knowledge, this is the first report of antesitum resection for IVC-LMS from India. A 51-year-old lady presented with features of Budd-Chiari syndrome and abdominal pain. Evaluation showed the tumor arising from IVC extending from above the renal veins and upto the subdiaphragmatic IVC. Blood investigations were normal with a positron emission tomography scan showing no metastatic disease. Antesitum, in situ resection of the IVC-LMS was performed. The patient recovered well postoperatively without renal or hepatic issues. Radical resection of IVC-LMS offers a chance for cure even in locally advanced status. Experience in complex liver resection and liver transplantation has made the resection of such tumors possible and safe.

Infiltrative cardiomyopathies are an increasingly recognized cause of heart failure warranting systematic evaluation. Given overlap of clinical and imaging findings among etiologies of infiltrative cardiomyopathies, comprehensive evaluation, including a history and physical examination, advanced cardiac imaging, and sometimes endomyocardial biopsy, is required for diagnosis. We report a case of infiltrative cardiomyopathy in which endomyocardial biopsy confirmed diagnosis of cobalt-induced cardiomyopathy. The novel teaching points highlighted by this case report include identification of heavy-metal toxicity as a cause of infiltrative cardiomyopathy, and the outline of a diagnostic approach and management for cobalt-induced cardiomyopathy.

Immune cell infiltration has been implicated in neurotoxic chemotherapy for cancer treatment. However, our understanding of immune processes is still incomplete and current methods of observing immune cells are time consuming or invasive. Corneal dendritic cells are potent antigen-presenting cells and can be imaged with in-vivo corneal confocal microscopy. Corneal dendritic cell densities and nerve parameters in patients treated with neurotoxic chemotherapy were investigated. Patients treated for cancer with oxaliplatin (n = 39) or paclitaxel (n = 48), 3 to 24 months prior to assessment were recruited along with 40 healthy controls. Immature (ImDC), mature (MDC) and total dendritic cell densities (TotalDC), and corneal nerve parameters were analyzed from in-vivo corneal confocal microscopy images. ImDC was increased in the oxaliplatin group (Median, Md = 22.7 cells/mm2) compared to healthy controls (Md = 10.1 cells/mm2, p = 0.001), but not in the paclitaxel group (Md = 10.6 cells/mm2). ImDC was also associated with higher oxaliplatin cumulative dose (r = 0.33, p = 0.04) and treatment cycles (r = 0.40, p = 0.01). There was no significant difference in MDC between the three groups (p > 0.05). Corneal nerve parameters were reduced in both oxaliplatin and paclitaxel groups compared to healthy controls (p

Background: Keratoconus is a condition characterized by biomechanical instability of cornea presenting in a progressive asymmetry and bilateral way. Corneal collagen cross-linking with riboflavin and UVA is a technique that has influenced the treatment of Keratoconus by arresting the progression. Aims and Objectives: The aim of the study was to assess the short-term efficacy and safety of collagen cross-linking in Keratoconus. Materials and Methods: This prospective, nonrandomized, interventional case study was conducted at Aravind Eye hospital and PGI, Puducherry from June 2012 to April 2013. Statistical analysis was done using repeated measures ANOVA and Bonferonn’s using IBM SPSS Inc. 20.Version. Results: A total of 30 patients were enrolled in this study and standard cross linking procedure was done. It was found that UCVA, BSCVA both improved about 40%. Spherical Equivalent reduced by 0.7 D, cylinder reduced by 0.8 D and total astigmatism decreased by about 0.4 D. Steepest K value reduced by 2 D, Irregularity and astigmatism at 3 and 5 mm also changed significantly (P

Myeloproliferative neoplasms (MPNs) are a group of malignant disorders of the bone marrow where a dysregulated balance between proliferation and differentiation gives rise to abnormal numbers of mature blood cells. MPNs encompass a spectrum of disease entities with progressively more severe clinical features, including complications with thrombosis and hemostasis and an increased propensity for transformation to acute myeloid leukemia. There is an unmet clinical need for markers of disease progression. Our understanding of the precise mechanisms that influence pathogenesis and disease progression has been limited by access to disease-specific cells as biosources. Here, we review the landscape of MPN pathology and present blood platelets as potential candidates for disease-specific understanding. We conclude with our recent work discovering progressive platelet heterogeneity by subtype in a large clinical cohort of patients with MPN. Graphic Abstract: A graphic abstract is available for this article.

Study Design: Retrospective case series.Purpose: This study aimed to examine the efficacy of composite grip strength as a marker of surgical outcome in patients with moderate to severe degenerative cervical myelopathy.Overview of Literature: Degenerative cervical myelopathy causes loss of dexterity, muscle strength, and sensations in the hand. The impact of surgical management on improvement in composite grip strength has received scant attention.Methods: This retrospective study was performed on degenerative cervical myelopathy patients with a complete composite grip strength assessment between January 2013 to January 2019. The Biometrics E-link hand kit was used for the assessment. The following parameters were measured: maximum grip strength, sustained grip strength, three-jaw pinch, maximum key pinch, and sustained key pinch. The pre- and postoperative functional status was assessed using the Nurick grade and the modified Japanese Orthopaedic Association (mJOA) score.Results: A total of 40 patients were included in the study. The mean patient age was 51.9 years. The mean preoperative Nurick grade was 3.5 and the mJOA score was 10.9. The anterior approach was used in 25 patients, and the posterior approach was used in 15 patients. Four patients developed complications. Degenerative cervical myelopathy resulted in decreased handgrip and pinch strength as compared to normative Indian data. There was a significant improvement in the postoperative composite grip strength for all five parameters. There was no differential improvement between the anterior and posterior surgical groups. The improvement in the composite grip strength correlated with the improvement in functional scores.Conclusions: Composite grip strength analysis is an objective method for assessing the impact of degenerative cervical myelopathy on grip strength and monitoring the postoperative improvement. Decompressive surgery resulted in global improvement in all the parameters of composite grip strength.

Adverse event reporting systems are important tools for identifying areas of risk and opportunities for education and improvement. Our goal was to examine the nature of perioperative incident reports related to care coordination that were filed by staff at an academic tertiary care center. In this retrospective data review, perioperative safety reports between 2015 and 2020 were analyzed. Information examined included the type of staff who initiated the report, location of the incident, type of incident and the severity level of event, including patient harm. Out of the 7827 reports evaluated, 61.2% of reports were filed by nurses, and 5.6% by physicians. We investigated one particular category called "coordination of care" and found the specific event most commonly reported was insufficient handoff (15.0%-26.9%), with severity level reported primarily being no to minor harm reaching the patient. However, communication failures were judged to be one of leading causes of inadvertent harm. It is imperative for hospital incident reporting systems to collect data on issues related to communication failures and to design interventions with the help of frontline staff to provide high quality, safe care to patients and to remain compliant with regulatory requirements and hospital policies.

Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.

PURPOSE Congenital spinal deformities (CSD) are uncommon; and usually present during early childhood. Rarely, patients have been reported to present with neglected CSD in association with myelopathy. The current study reports the largest series of patients with neglected CSD and major neuro-deficit; and discusses their long-term outcome. METHODS We retrospectively analysed patients with CSD who presented with myelopathy and underwent surgical management between January 2008 and January 2018. Only patients who had complete clinico-radiological records and completed minimum 2-year follow-up were included. Neurology was graded according to American Spinal Injury Association Impairment, Nurick and modified Japanese Orthopaedic Association scores. Radiological details like deformity type, location, magnitude, and underlying anomaly were recorded. A comparative analysis of parameters between pre-operative and final follow-up periods was performed. RESULTS Thirty three (age = 21.1 ± 11.9 years) patients with CSD and myelopathy were included. Mean duration since myelopathy was 5.2 ± 6.2 months. Thirty (91%) patients presented with kyphosis or kyphoscoliosis; and 18 had upper thoracic-level lesion (12 and 3 with mid- or low-thoracic and lumbar lesions). 16 (48.5%) and 12 (36.4%) presented with types 1 and 3 anomalies, respectively. Mean pre-operative mJOA and Nurick grades were 8.8 ± 2.4 and 3.4 ± 0.7. Based on ASIA score, 2, 5, 21 and five patients presented with grades A, C, D and E, respectively. All patients underwent surgeries from posterior-only approach. Mean follow-up was 4.7 ± 2.6 years. In kyphoscoliosis group, coronal and sagittal Cobb improved by 23.8° and 25.9°, respectively. Mean deformity improved by 19.6° and 15.6° in scoliosis and kyphosis groups, respectively. Neurological status improved in 5, remained stable in 23 and deteriorated in five patients. Mean mJOA and Nurick grades at final follow-up was 8.3 ± 3.1and 3.4 ± 0.9. CONCLUSION Major neurological deficit is a rare complication of neglected CSD. In our series, such a presentation was observed in patients with kyphotic or kyphoscoliotic deformities, type 1 or 3 vertebral anomalies and proximal thoracic vertebral lesions. Surgery can be valuable in these patients, as it not only stabilises deformity, but also provides the best chance of preventing neuro-deterioration.

Purpose of review The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions. Recent findings Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources. Summary Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.

Ischemic stroke in the Posterior Cerebral Artery (PCA) territory is an uncommon entity. Majority present with visual field defects while isolated visual perceptual abnormalities are an exceptional manifestation. About 60 year old hypertensive patient presented with vague symptoms of blurring of vision and palinopsia. Defective color vision was recorded in superior quadrants. Perimetry revealed bilateral congruous left superior quadrantanopia. Magnetic Resonance Imaging (MRI) disclosed right PCA infarct involving occipito-temporal region. This case highlights a rare presentation of PCA stroke with palinopsia and cerebral dyschromatopsia. Perimetric examination coupled with urgent neuroimaging helps the clinician in prompt diagnosis of neurological event causing unexplained visual phenomena.

We assessed the clinical outcomes of patients with critical limb-threatening ischemia (CLTI) who underwent interwoven nitinol stent (Supera) implantation for significant stenoses of the femoropopliteal segment. In this retrospective cohort study, 116 consecutive patients with CLTI who were treated with Supera stents between September 2015 and March 2020 were included in this analysis. Primary endpoint analysis was completed for amputation-free survival, target lesion revascularization (TLR), and mortality. After a mean follow-up time of 3.4 years, 21 (18%) patients had undergone amputations, 3 (2.6%) died, and, overall, the amputation-free survival rate was 81%. TLR occurred in 21 (18%) patients, resulting in the freedom from target lesion revascularization of 82%. The average Wagner score for all patients was 2.8 ± 1.1. A subgroup analysis of 57 patients revealed a median ulcer size of 3.0 cm2 [1.65, 9.0], with complete healing for 45 patients by 20 months. The Wagner score of this subgroup decreased by an average of 3.4 ± .9 points. Supera stents can be used together with other endovascular therapies and are a safe and effective treatment modality for CLTI.