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We undertook this study to determine the safe limits of capsulorhexis during nucleus expression in 40 eyes of patients undergoing extracapsular cataract extraction (ECCE) with a posterior chamber intraocular lens (PC IOL) implantation and in 30 cadaver eyes. In group I (patient eyes), capsulorhexis of 4.5 to 7.5 mm was performed and the nucleus was expressed by hydrodissection. The nuclei measured 4.5 to 9.0 mm. One relaxing incision at 12 o′clock position had to be placed in 9 patients. In group II (cadaver eyes), continuous curvilinear capsulotomies of 4.0, 4.5, 5.0, 5.5, 6.0 and 6.5 mm were made in 5 eyes each. No relaxing incisions were placed. In both the groups, nuclei of all sizes could be safely delivered through intact capsulotomies measuring 5.5 mm or more. In two patient eyes, posterior capsule rupture occurred with rhexis measuring 4.5 and 5.0 mm, respectively. In the cadaver eyes, intracapsular extraction occurred in 4 eyes with rhexis measuring 5.0 mm or less. We conclude that a rhexis less than 5.5 mm is not safe for nucleus delivery during ECCE.

Abstract Background This phase 1b study assessed the maximum tolerated dose (MTD), safety, and pharmacokinetics of motesanib (a small-molecule antagonist of VEGF receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit) administered once daily (QD) or twice daily (BID) in combination with erlotinib and gemcitabine in patients with solid tumors. Methods Patients received weekly intravenous gemcitabine (1000 mg/m2) and erlotinib (100 mg QD) alone (control cohort) or in combination with motesanib (50 mg QD, 75 mg BID, 125 mg QD, or 100 mg QD; cohorts 1-4); or erlotinib (150 mg QD) in combination with motesanib (100 or 125 mg QD; cohorts 5 and 6). Results Fifty-six patients were enrolled and received protocol-specified treatment. Dose-limiting toxicities occurred in 11 patients in cohorts 1 (n = 2), 2 (n = 4), 3 (n = 3), and 6 (n = 2). The MTD of motesanib in combination with gemcitabine and erlotinib was 100 mg QD. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Frequently occurring motesanib-related adverse events included diarrhea (n = 19), nausea (n = 18), vomiting (n = 13), and fatigue (n = 12), which were mostly of worst grade < 3. The pharmacokinetics of motesanib was not markedly affected by coadministration of gemcitabine and erlotinib, or erlotinib alone. Erlotinib exposure, however, appeared lower after coadministration with gemcitabine and/or motesanib. Of 49 evaluable patients, 1 had a confirmed partial response and 26 had stable disease. Conclusions Treatment with motesanib 100 mg QD plus erlotinib and gemcitabine was tolerable. Motesanib 125 mg QD was tolerable only in combination with erlotinib alone. Trial Registration ClinicalTrials.gov NCT01235416

Metastases to the heart are extremely uncommon. We describe three unusual cases along with their management. A review of the current literature concerning cardiac secondaries is included.

Abstract Background The quality of diabetes care provided to older adults has usually been judged to be poor, but few data provide direct comparison to other age groups. In this study, we hypothesized that adults age 65 and over receive lower quality diabetes care than adults age 45–64 years old. Methods We conducted a cohort study of members of a health plan cared for by multiple medical groups in Minnesota. Study subjects were a random sample of 1109 adults age 45 and over with an established diagnosis of diabetes using a diabetes identification method with estimated sensitivity 0.91 and positive predictive value 0.94. Survey data (response rate 86.2%) and administrative databases were used to assess diabetes severity, glycemic control, quality of life, microvascular and macrovascular risks and complications, preventive care, utilization, and perceptions of diabetes. Results Compared to those aged 45–64 years (N = 627), those 65 and older (N = 482) had better glycemic control, better health-related behaviors, and perceived less adverse impacts of diabetes on their quality of life despite longer duration of diabetes and a prevalence of cardiovascular disease twice that of younger patients. Older patients did not ascribe heart disease to their diabetes. Younger adults often had explanatory models of diabetes that interfere with effective and aggressive care, and accessed care less frequently. Overall, only 37% of patients were simultaneously up-to-date on eye exams, foot exams, and glycated hemoglobin (A1c) tests within one year. Conclusion These data demonstrate the need for further improvement in diabetes care for all patients, and suggest that customisation of care based on age and explanatory models of diabetes may be an improvement strategy that merits further evaluation.

Internal hernias (IHs) are defined as the protrusion of the intestine through an aperture in the peritoneal ligament, mesentery, or the omentum, without traversing the fascial planes and leading to encapsulation of the protruded intestine within another compartment of an otherwise intact abdominal cavity. Internal hernias can be acquired or congenital. Congenital internal hernias resulting in small bowel obstruction are extremely rare, even more so in adults, occurring usually due to embryological or developmental defects, often undiagnosed, and requiring a high index of clinical suspicion. We report a rare case of a 22-year-old young adult with transmesenteric hernia of distal ileum through a congenital distal ileal mesenteric defect resulting in closed-loop small bowel obstruction and distal ileal gangrene, managed with resection and end-ileostomy, followed by stoma reversal one month later. It requires a high index of suspicion and remains a surgical emergency due to its predilection for intestinal gangrene and small bowel obstruction, with a high mortality rate due to delayed presentation and diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Songadkar et al.)

In the present work, various chemical exfoliation routes for semiconducting two-dimensional (2D) layered material WS 2 are explored, which include magnetic stirring (MS), shear mixing (SM), and horn-tip (HT) sonication. Current-voltage measurements, Raman spectroscopy, and photoluminescence (PL) spectroscopy were used to characterize the drop-casted WS 2 nanosheets produced by these three techniques and our analysis revealed that HT sonication produced the most optimal dispersions. Heterostructure photodetector devices were then fabricated using inkjet printing of the HT sonicated dispersions of WS 2 and graphene. The photodetector device performance was measured using a stream of ON/OFF light pulses generated using a red laser with wavelength λ ∼ 660 nm, and an arbitrary waveform generator. From this analysis, the photoresponsivity and detectivity of the graphene-WS 2 -graphene heterostructure devices were calculated to be ∼0.86 A W -1 and ∼10 13 Jones, respectively. Capacitance-voltage ( C - V ) and C -frequency ( f ) measurements were also conducted, where the V was swept from -6 V to +6 V, while the change in C was measured from f ∼ 20 kHz up to 3 MHz to gain insights into the nature of the graphene-WS 2 interface. From the C - V measurements, the C plateaued at ∼324.3 pF from ∼-4 V to +4 V for the lowest f of 20 kHz and it reduced to ∼200 pF from -6 V to ∼-4 V, and similarly from ∼4 V to 6 V, C was ∼190 pF. The decrease in C for V > +4 V and V < -4 V was attributed to the reduction of the interfacial barrier at the electrodes which is suggestive of a Schottky-based photodiode at the graphene-WS 2 interface. A sharp decrease in C from ∼315.75 pF at 25.76 kHz to ∼23.79 pF at 480 kHz (at 0 V bias) from the C - f measurements suggests a strong effect of interface trap density on C built-up at the graphene-WS 2 interface and the ensuing Schottky barrier height. Our work confirms the excellent potential of solution-cast, trilayer graphene-WS 2 -graphene heterostructures as a promising photodetector platform using additively manufactured inkjet printing., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Stable ink dispersions of two-dimensional-layered-materials (2DLMs) MoS 2 and graphite are successfully obtained in organic solvents exhibiting a wide range of polarities and surface energies. The role of sonication time, ink viscosity and surface tension is explored in the context of dispersion stability using these solvents, which include N-methyl-2-pyrrolidone (NMP), N,N-Dimethylacetamide (DMA), dimethylformamide (DMF), Cyclohexanone (C), as well as less-toxic and more environmentally friendly Isopropanol (IPA) and Terpineol (T). The ink viscosity is engineered through the addition of Ethyl-Cellulose (EC) which has been shown to optimize the jettability of the dispersions. In contrast to prior work, the addition of EC after sonication-instead of prior to it-is noted to be effective in generating a high-density dispersion, yielding a uniform film morphology. High-quality inks are obtained using C/T and NMP as solvents for MoS 2 and graphite, respectively, as gauged through optical absorption spectroscopy. Electronic transport data on the solution-cast inks is gathered at room temperature. Arrays of 2D graphite-rod based inks are printed on rigid Si, as well as flexible and transparent polyethylene terephthalate (PET) substrates. The results clearly show the promise of ink-jet printing for casting 2DLMs into hierarchically assembled structures over a range of substrates for flexible and printed-electronics applications.

Kinesthesia is our sense of limb motion, and allows us to gauge the speed, direction, and amplitude of our movements. Over half of stroke survivors have significant impairments in kinesthesia, which leads to greatly reduced recovery and function in everyday activities. Despite the high reported incidence of kinesthetic deficits after stroke, very little is known about how damage beyond just primary somatosensory areas affects kinesthesia. Stroke provides an ideal model to examine structure-function relationships specific to kinesthetic processing, by comparing lesion location with behavioral impairment. To examine this relationship, we performed voxel-based lesion-symptom mapping and statistical region of interest analyses on a large sample of sub-acute stroke subjects ( N = 142) and compared kinesthetic performance with stroke lesion location. Subjects with first unilateral, ischemic stroke underwent neuroimaging and a comprehensive robotic kinesthetic assessment (~9 days post-stroke). The robotic exoskeleton measured subjects' ability to perform a kinesthetic mirror-matching task of the upper limbs without vision. The robot moved the stroke-affected arm and subjects' mirror-matched the movement with the unaffected arm. We found that lesions both within and outside primary somatosensory cortex were associated with significant kinesthetic impairments. Further, sub-components of kinesthesia were associated with different lesion locations. Impairments in speed perception were primarily associated with lesions to the right post-central and supramarginal gyri whereas impairments in amplitude of movement perception were primarily associated with lesions in the right pre-central gyrus, anterior insula, and superior temporal gyrus. Impairments in perception of movement direction were associated with lesions to bilateral post-central and supramarginal gyri, right superior temporal gyrus and parietal operculum. All measures of impairment shared a common association with damage to the right supramarginal gyrus. These results suggest that processing of kinesthetic information occurs beyond traditional sensorimotor areas. Additionally, this dissociation between kinesthetic sub-components may indicate specialized processing in these brain areas that form a larger distributed network.

It is well established that proprioceptive inputs from the periphery are important for the constant update of arm position for perception and guiding motor action. The degree to which we are consciously aware of the position of our limb depends on the task. Our understanding of the central processing of position sense is rather limited, largely based on findings in animals and individual human case studies. The present study used statistical lesion-behavior analysis and an arm position matching task to investigate position sense in a large sample of subjects after acute stroke. We excluded subjects who performed abnormally on clinical testing or a robotic visually guided reaching task with their matching arm in order to minimize the potential confound of ipsilesional impairment. Our findings revealed that a number of regions are important for processing position sense and include the posterior parietal cortex, the transverse temporal gyrus, and the arcuate fasciculus. Further, our results revealed that position sense has dissociable components - spatial variability, perceived workspace area, and perceived workspace location. Each component is associated with unique neuroanatomical correlates. These findings extend the current understanding of the neural processing of position sense and identify some brain areas that are not classically associated with proprioception., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Echocardiography is often performed to identify a cardiac source of embolism (CSE) causing transient ischemic attack (TIA). However, the diagnostic yield of echocardiography in TIA remains uncertain, and its role in routine evaluation of TIA is controversial., Methods: Patients with acute TIA were prospectively enrolled at 4 stroke centers. A CSE was defined using the Causative Classification of Stroke system; patent foramen ovale was considered a relevant CSE only if the patient underwent closure or was placed on anticoagulation. Patients with a known CSE at time of admission were excluded from analysis of the yield of echocardiography., Results: A total of 869 patients were enrolled at stroke centers, and 129 had a known CSE at presentation. Of the 740 remaining patients, 603 (81%) underwent echocardiography. A potential CSE was identified in 60 (10%) of these patients. The most common CSEs noted on echocardiography were complex aortic arch atherosclerosis and patent foramen ovale. History of coronary artery disease (P < .001), lack of prior stroke or TIA (P = .007), and presence of acute infarction on magnetic resonance imaging (MRI) (P < .001) were predictors of CSE on echocardiography. The yield of echocardiography was 29% in patients with both history of coronary artery disease and acute infarction on MRI, 14% with one of these features, and 5% with neither of these features (P < .0001). A CSE identified by echocardiography prompted initiation of anticoagulation in 15 of the 603 (2.5%) subjects., Conclusions: Echocardiography demonstrates a relevant CSE in a significant portion of patients with TIA. However, changes in antithrombotic therapy resulting from echocardiography are infrequent., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Objectives: The National Quality Forum recently endorsed a performance measure for time to intravenous thrombolytic therapy which allows exclusions for circumstances in which fast alteplase treatment may not be possible. However, the frequency and impact of unavoidable patient reasons for long door-to-needle time (DNT), such as need for medical stabilization, are largely unknown in clinical practice. As part of the Hurry Acute Stroke Treatment and Evaluation-2 (HASTE-2) project, we sought to identify patient and systems reasons associated with longer DNT., Methods: From June 2012 to June 2013 we collected data on DNT and potential reasons for delays from 102 consecutive patients presenting directly to the emergency department who were treated with alteplase within 4.5 hours of symptom onset., Results: Mean age was 71 years, 56/113 (54%) were women, median NIH Stroke Scale score was 13, and median DNT was 53 minutes. Potential delays were noted in 59/102 (58%), of which 31/102 (31%) were unavoidable patient-related or eligibility reasons. Median DNT was longer when patient-related or eligibility reasons for delay were present (60 minutes) than when absent (45 minutes, p = 0.005). Multivariable modeling showed that need for urgent medical stabilization, presentation with seizure and inability to confirm eligibility were associated with 35%-50% longer DNT times., Conclusions: Up to 31% of patients have delays due to medical or eligibility-related causes that may be legitimate reasons for providing alteplase later than the benchmark time of 60 minutes., (© 2016 by the Society for Academic Emergency Medicine.)

Visuospatial neglect is a disorder that can often result from stroke and is characterized by an inability to attend to contralesional stimuli. Two common subtypes include allocentric (object-centered) neglect and egocentric (viewer-centered) neglect. In allocentric neglect, spatial inattention is localized to the contralesional side of an object regardless of its relative position to the observer. In egocentric neglect, spatial inattention is localized to the contralesional side of the individual's midline. The neuroanatomical correlates of each subtype are unknown. However, recent work has suggested that damage to temporal, inferior parietal, and occipital areas may result in allocentric neglect and that damage to frontoparietal areas may result in egocentric neglect. We used voxel-based lesion-symptom mapping (VLSM) to compare lesion location to behavioral performance on the conventional six subtests of the Behavioral Inattention Test (BIT) in 62 subjects with acute right hemisphere ischemic stroke. Results identified an anatomical dissociation in lesion location between subjects with neglect based on poor performance on allocentric tests (line bisection, copying, and drawing tasks) and on egocentric tests (star, letter, and line cancellation). VLSM analyses revealed that poor performance on the allocentric tests was associated with lesions to the superior and inferior parietal cortices, and the superior and middle temporal gyri. In contrast, poor performance on the egocentric tests was associated with lesions in the precentral gyrus, middle frontal gyrus, insula, and putamen. Interestingly, the letter cancellation test and average performance on egocentric tests were associated with frontal and parietal lesions. Some of these parietal lesion locations overlapped with lesion locations associated with allocentric neglect. These findings are consistent with suggestions that damage to temporal and parietal areas is more associated with allocentric neglect and damage to frontal lobe areas is more associated with egocentric neglect.

Background: Stentrievers have resulted in faster recanalization times in patients with acute ischemic stroke. Nonetheless, when strokes occur during evenings and weekends, delays are introduced in achieving this goal. We assessed the feasibility of achieving fast and successful endovascular reperfusion in patients with stroke treated during evenings and weekends and whether this has an impact on the outcome., Methods: A retrospective review was performed of a longitudinal database of patients with acute anterior ischemic stroke treated with endovascular therapy in a comprehensive stroke center between January 2011 and December 2012. The imaging to reperfusion time was defined as the time from completion of the unenhanced CT scan to the time of angiographic successful reperfusion (TICI 2b-3). This time interval was compared between patients treated during working hours (Monday to Friday 07:00-18:00 h) and those treated in the evening outside these hours and at weekends. The 24-h NIH Stroke Scale score and 90-day favorable outcome score (modified Rankin scale ≤2) were compared between the two groups., Results: In a cohort of 110 patients, 56 (50.9%) were treated on evenings and weekends. The median imaging to reperfusion time in these patients was 111 min compared with 90 min during working hours (p=0.019). The proportion of patients with successful reperfusion (TICI 2b or 3) during the evenings and weekends was 82.1% compared with 76.7% during working hours (p=0.4). The proportion of patients with a 90-day favorable outcome was not significantly different in the two groups (64.3% in those treated during evenings and weekends vs 52.1% in working hours, p=0.2)., Conclusions: Some delays were encountered during evenings and weekend hours. Despite that, it was feasible to achieve a relatively short imaging to reperfusion times during these hours, in comparison to existing literature. A target universal time metric is needed to assess the timeliness of endovascular therapy in stroke centers., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

A middle aged patient presented with acute ischemic stroke due to basilar artery occlusion. The patient clinically deteriorated despite intravenous thrombolysis and was referred for mechanical thrombectomy. The right vertebral artery was occluded and could not be accessed despite attempting various shaped catheters, even when a radial artery access was used. The left vertebral artery ended in the posterior inferior cerebellar artery. Eventually, ultrasound guided V3 segment vertebral artery direct puncture was successfully done and the procedure was completed. No access related complications were encountered. Direct cervical arterial puncture can be safely used by experienced operators as a last resort in acute stroke cases with difficult access.

Background: The assortment of patients based on the underlying pathophysiology is central to preventing recurrent stroke after a transient ischemic attack and minor stroke (TIA-MS). The causative classification of stroke (CCS) and the A-S-C-O (A for atherosclerosis, S for small vessel disease, C for Cardiac source, O for other cause) classification schemes have recently been developed. These systems have not been specifically applied to the TIA-MS population. We hypothesized that both CCS and A-S-C-O would increase the proportion of patients with a definitive etiologic mechanism for TIA-MS as compared with TOAST., Methods: Patients were analyzed from the CATCH study. A single-stroke physician assigned all patients to an etiologic subtype using published algorithms for TOAST, CCS and ASCO. We compared the proportions in the various categories for each classification scheme and then the association with stroke progression or recurrence was assessed., Results: TOAST, CCS and A-S-C-O classification schemes were applied in 469 TIA-MS patients. When compared to TOAST both CCS (58.0 vs. 65.3%; p < 0.0001) and ASCO grade 1 or 2 (37.5 vs. 65.3%; p < 0.0001) assigned fewer patients as cause undetermined. CCS had increased assignment of cardioembolism (+3.8%, p = 0.0001) as compared with TOAST. ASCO grade 1 or 2 had increased assignment of cardioembolism (+8.5%, p < 0.0001), large artery atherosclerosis (+14.9%, p < 0.0001) and small artery occlusion (+4.3%, p < 0.0001) as compared with TOAST. Compared with CCS, using ASCO resulted in a 20.5% absolute reduction in patients assigned to the 'cause undetermined' category (p < 0.0001). Patients who had multiple high-risk etiologies either by CCS or ASCO classification or an ASCO undetermined classification had a higher chance of having a recurrent event., Conclusion: Both CCS and ASCO schemes reduce the proportion of TIA and minor stroke patients classified as 'cause undetermined.' ASCO resulted in the fewest patients classified as cause undetermined. Stroke recurrence after TIA-MS is highest in patients with multiple high-risk etiologies or cryptogenic stroke classified by ASCO., (© 2014 S. Karger AG, Basel.)

Rapid reperfusion of the entire territory distal to vascular occlusions is the aim of stroke interventions. Recent studies defined successful reperfusion as establishing some perfusion with distal branch filling of <50% of territory visualized (Thrombolysis In Cerebral Infarction "TICI" 2a) or more. We investigate the importance of the quality of final reperfusion and whether a revision of the successful reperfusion definition is warranted. We retrospectively evaluated a prospective database of anterior circulation strokes treated using stentrievers to assess the quality of final reperfusion using two scores: the traditional TICI score and a modified TICI score. The modified TICI score includes an additional category (TICI 2c): near complete perfusion except for slow flow or distal emboli in a few distal cortical vessels. We compared different cut-off definitions of reperfusion (TICI 2a - 3 vs. TICI-2b-3 vs. TICI 2c-3) using the area under the curve to identify their correlation with a favorable 90-day outcome (mRS≤2). In our cohort of 110 patients, 90% achieved TICI 2a-3 reperfusion with 80% achieving TICI 2b-3 and 55.5% achieving TICI 2c-3. The proportion of patients with a favorable 90-day outcome was higher in the TICI 2c (62.5%) compared to TICI 2b (44.4%) or TICI 2a (45.5%) but similar to the TICI 3 group (75.9%). A TICI 2c-3 reperfusion had a better predictive value than TICI 2b-3 for 90-day mRS 0-1. Defining successful reperfusion as TICI 2c/3 has merits. In this cohort, there was evidence toward faster recovery and better outcomes in patients with the TICI 2c vs. the traditional TICI 2b grade.

In acute ischemic stroke, time is brain. Current guidelines recommend that the time from arrival at hospital to initiation of administration of tissue plasminogen activator, also known as the door-to-needle (DTN) time, should be 60 min or less. However, DTN times in practice usually exceed this recommended time. The median DTN times from the American Heart Association/American Stroke Association Get With The Guidelines-Stroke program and the multinational Safe Implementation of Treatment in Stroke International Stroke Thrombolysis Register are 75 min and 65 min, respectively. Prehospital factors associated with delays include patient-related factors such as poor recognition of stroke symptoms, poor use of emergency medical services, and complex psychosocial factors. Accurate recognition of stroke symptoms at a dispatcher and paramedic level is associated with shorter onset-to-arrival times. Prenotification of regional stroke centers by paramedics is strongly associated with shorter DTN times. In-hospital delays resulting in prolonged DTN times can be attenuated by having well-defined rapid triage pathways, defined stroke teams, single-call stroke team activation, established code stroke protocols, rapid access to diagnostic imaging, and laboratory services. In this review we summarize factors associated with prolonged DTN times and processes that allow faster onset-to-treatment times. Recent developments in the field are highlighted.

A middle aged patient presented with acute ischemic stroke due to basilar artery occlusion. The patient clinically deteriorated despite intravenous thrombolysis and was referred for mechanical thrombectomy. The right vertebral artery was occluded and could not be accessed despite attempting various shaped catheters, even when a radial artery access was used. The left vertebral artery ended in the posterior inferior cerebellar artery. Eventually, ultrasound guided V3 segment vertebral artery direct puncture was successfully done and the procedure was completed. No access related complications were encountered. Direct cervical arterial puncture can be safely used by experienced operators as a last resort in acute stroke cases with difficult access.

Lyme disease caused by the spirochete Borrelia burgdorferi is a multisystem disorder characterized by three clinical stages: dermatologic, neurologic, and rheumatologic. The number of known Lyme disease-endemic areas in Canada is increasing as the range of the vector Ixodes scapularis expands into the eastern and central provinces. Southern Ontario, Nova Scotia, southern Manitoba, New Brunswick, and southern Quebec are now considered Lyme disease-endemic regions in Canada. The use of field surveillance to map risk and endemic regions suggests that these geographic areas are growing, in part due to the effects of climate warming. Peripheral facial nerve palsy is the most common neurologic abnormality in the second stage of Lyme borreliosis, with up to 25% of Bell palsy (idiopathic peripheral facial nerve palsy) occurring due to Lyme disease. Here we present a case of occult bilateral facial nerve palsy due to Lyme disease initially diagnosed as Bell palsy. In Lyme disease-endemic regions of Canada, patients presenting with unilateral or bilateral peripheral facial nerve palsy should be evaluated for Lyme disease with serologic testing to avoid misdiagnosis. Serologic testing should not delay initiation of appropriate treatment for presumed Bell palsy.