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Objective: The efficacy of middle meningeal artery (MMA) embolization in the management of chronic subdural hematoma (cSDH) has been increasingly supported by recent randomized controlled trials. However, long-term data on the natural history of cSDH post-treatment remain limited. This study aims to evaluate the natural history and outcomes of cSDH over a 12-month period following MMA embolization., Methods: We conducted a retrospective analysis of 61 MMA embolization for the treatment of cSDH in 49 consecutive patients at a single institution between October 2019 and December 2022. Patients underwent MMA embolization as the primary treatment of cSDH, concurrently with surgical evacuation, or after initial surgical evacuation and subsequent recurrence. Clinical data, including patient demographics, hematoma maximal thickness, midline shift size, procedural details, and outcomes, were collected and analyzed. The primary outcomes assessed were time to resolution of hematoma maximal thickness, midline shift reduction and clinical improvement. Secondary outcomes included occurrence of complications, recurrence rate and the characteristics of the group of patients who needed surgical rescue. Tables and Kaplan-Meier curves were created, broken down by the percentage of reduction in current hematoma maximal thickness. Results for the primary, concurrent and recurrent groups were compared., Results: The mean age of included patients was 73 ± 10.8 years. Among them, 33 patients (67.3%) reported a history of previous trauma, with falls being the main mechanism of injury (65.3%). The majority of patients (77.5%) were male. The most frequent neurological symptom was headache (61.2%). The mean hematoma thickness and midline shift were 15.9±7.1 and 5.6±2.6 mm, respectively. There was a significant improvement in clinical symptoms within 1 month following middle meningeal artery embolization. Kaplan-Meier curves were generated for resolution of hematoma size and midline shift. At one month post procedure, only 25% of patients had at least a 25% reduction in hematoma size. However, by three months, 75% had a decrease in hematoma size by 50%. 85% of patients had complete resolution of hematoma by 7 months and all patients had resolution of hematoma by 12 months. Four patients underwent surgical rescue hematoma evacuation and the mean timeframe between the embolization and the surgical rescue was 2 weeks. Hematoma size and midline shift resolved faster for patients who underwent concurrent or rescue surgical evacuation of the hematoma in addition to embolization. No difference in results between the liquid embolics n-BCA and Onyx-18 was found., Conclusion: This study demonstrated a favorable resolution of subdural hematoma within 7 months in 85% of patients and in all patients by 12 months. By 3 months, 50% of patients had a decrease in hematoma size by 50% or more. A complete resolution of midline shift within 7 months, and a significant improvement in clinical symptoms within 1 month following middle meningeal artery embolization. Hematoma size and midline shift resolved faster for patients who underwent embolization for recurrent hematoma or concurrent surgical evacuation of the hematoma in addition to embolization., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: Laser interstitial thermal therapy (LITT) has demonstrated promise in surgical neuro-oncology because of its effectiveness in delivering precise thermal energy to lesions. The extent of ablation (EOA) is a prognostic factor in improving patient outcomes but is often affected by perilesional heatsink structures, which can lead to asymmetric ablations. The purpose of this study was to quantitatively evaluate the impact of various perilesional heatsink structures on the EOA in LITT for brain metastases., Methods: Twenty-seven procedures for 22 unique patients with brain metastases fit the inclusion criteria. Intracranial heatsink structures were identified: sulci, meninges, cerebrospinal fluid (CSF) spaces, and vasculature. Asymmetric ablation was determined by measuring 3 pairs of orthogonal distances from the proximal, midpoint, and distal locations along the laser catheter to the farthest edge of the ablation zone bilaterally. Distances from the same points on the laser catheter to the nearest heatsink were also recorded. The Heatsink Effect Index was created to serve as a proxy for asymmetric ablation. Pearson correlations, t -tests, and analysis of variance were the statistical analyses performed., Results: From the midpoint of the catheter, the 27 heatsinks were meninges (40.7%), sulci (22.2%), vasculature (22.2%), and CSF spaces (14.8%). Across all points along the catheter track, there was a significant generalized heatsink effect on asymmetric ablations ( P < .0001). There was a negative correlation observed between asymmetric ablations and EOA from the midpoint of the laser catheter (r = -0.445, P = .020). Compared with sulci, CSF spaces trended toward a greater effect on asymmetric ablation volumes ( P = .069)., Conclusion: This novel quantitative analysis shows that perilesional heatsinks contribute to asymmetric ablations. CSF spaces trended toward higher degrees of asymmetric ablations. Importantly, neurosurgeons may anticipate asymmetric ablations preoperatively if heatsinks are located within 13.3 mm of the laser probe midpoint. These preliminary results may guide surgical decision-making in LITT for metastatic brain lesions., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background and Objective: Due to their academic load, medical students are highly susceptible to stress. Stress is one of the factors that can alter sleep quality which may consequently affect the cognitive performance of medical students. There has been a lack of published local literature that looks into the association between stress and sleep quality, especially during the COVID-19 pandemic. With this, the general objective of this study is to determine the effect of stress on the sleep quality of medical students from the University of the Philippines Manila - College of Medicine (UPCM)., Methods: A cross-sectional study was conducted using a stratified random sample of 273 males and females of Learning Unit (LU) III (1 st year) to VII (5 th year) medical students from a college of medicine based in the Philippines, UPCM, during the second semester of the academic year 2021-2022. A self-administered questionnaire was distributed to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI), and stress level using the Kessler Psychological Distress Scale (K10). Kruskal-Wallis was used to test statistical differences between stress scores and the sleep quality of students from different year levels. Spearman's Rho was used to determine the correlation between stress and sleep, and a binary logistic regression was employed to study the association of stress with sleep while accounting for confounding variables namely caffeine intake, year level, daytime nap, duty hours, clinical rotation, sex, and age., Results: A high prevalence of stress (79.71%) and poor sleep quality (59.73%) among LU III to LU VII UPCM students were found, with a statistically positive correlation (ρ=0.44) 95CI [0.33-0.55] (p-value<0.001). Both the stress scores and sleep quality indices were not statistically significantly different across LUs. Gathered data and interpreted results showed that medical students suffering from stress are more likely to have poor sleep quality, which can lead to low academic performance and high susceptibility to chronic diseases, compared to those medical students with low levels of stress. Only being an LU IV [OR=1.38 95CI (0.036-4.625)] and LU V [OR=2.13 95CI (0.296-6.936)] student had increased odds of having poor sleep quality compared to LU III students. Caffeine intake, daytime nap, duty hours, clinical rotation, sex, and age were not associated with poor sleep quality., Conclusion: This study documents a statistically significant association between stress and poor sleep quality among LU III to LU VII UPCM students. A larger study covering multiple medical schools in the Philippines may be of merit for future investigations to generate nationwide data. Additional recommendations include: a) conducting a cross-sectional or a longitudinal study to detect changes in the characteristics of the population, b) observing the differences in the contributing factors at multiple points throughout the year, c) investigating the effect of dwelling set-up on sleep quality may also be investigated and d) determining if sleep quality affects the level of perceived stress of medical students., Competing Interests: All authors declared no conflicts of interest., (© 2024 Acta Medica Philippina.)

Purpose: The past two decades have witnessed the rise of keyhole microscopic minimally invasive surgeries, including the transciliary supraorbital approach (TCA) and transpalpebral approach (TPA), commonly known as the transorbital approach. This study aims to elucidate the nuances, specific indications, and advantages of each approach., Methods: A series of dissections were conducted on five formalin-fixed, alcohol-preserved cadaver heads. The TCA was performed on one side, and the TPA on the other. Virtual measurements of working angles for both approaches were recorded. Additionally, three clinical cases were presented to illustrate the practical application of the techniques., Results: For TCA, the craniotomy dimensions were 1.7 cm x 2.5 cm (Cranial-Caudal (CC) x Lateral-Lateral (LL)), while for TPA, they measured 2.1 cm x 2.9 cm (CC x LL). The measurements of anterior clinoid processes (ACP) were obtained and compared between approaches. In the TCA, the mean ipsilateral ACP measurement was 62 mm (Range: 61 -63 mm), and the mean contralateral ACP measurement was 71.2 mm (Range: 70 -72 mm). In TPA, these measurements were 47.8 mm (Range: 47 -49 mm) and 62.8 mm (Range: 62 -64 mm), respectively. TCA exhibited an average cranial-caudal angle of 14.9°, while TPA demonstrated an average of 8.3°., Conclusion: The anterior cranial fossa was better exposed by a TCA, which also featured shorter operative times, enhanced midline visualization, and a quicker learning curve. Conversely, the middle fossa was better exposed by a TPA, making it an excellent option for middle fossa pathologies, including those in the anterior temporal lobe. After sphenoid bone wing drilling, the TPA offers superior visualization from the lateral to the medial aspect and enhances the CC angle. Additionally, the TPA reduces the risk of postoperative frontalis palsy based on anatomic landmarks. However, the TPA requires a greater cranial osteotomy, and due to unfamiliarity with eyelid anatomy, the learning curve for most neurosurgeons is lengthier for this procedure., (© 2024. The Author(s).)

Purpose: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms., Methods: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes., Results: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT)., Conclusion: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes., (© 2024. The Author(s).)

Background: Surgeons sustain deviated postures during procedures even with the use of loupes or an operative microscope. The surgical exoscope is a new intraoperative visualization technology designed to improve surgical ergonomics; however, no objective data exist to say that surgeon posture is significantly improved. This study aimed to quantify the difference in posture during standard anterior cervical spine procedures performed with the aid of an operative microscope versus an exoscope., Methods: This was a prospective cohort study utilizing a posture-sensing device at the surgeon's cervicothoracic junction. The primary outcome was the proportion of time under scope spent in a deviated posture, defined as greater than 10 degrees of deviation from neutral in the x- and y-axes (flexion/extension and lateral bending) of the surgeon's upper torso. Average deviation from baseline for the x-, y-, and z-axes (flexion/extension, lateral bending, and axial rotation, respectively), as well as the percentage of operative time spent with the visualization aid was also analyzed., Results: Overall, 37 anterior cervical procedures were recorded: 18 were performed with an exoscope and 19 with a microscope. Surgeons spent significantly more time in the deviated posture with the operative microscope than with the exoscope (32% vs. 8% with x-axis >10 deg, P <0.005; 20% vs. 6% with y-axis >10 deg, P <0.05). This is also reflected by the significant differences in the average deviation in the x- and y-axes, while under scope., Conclusions: Utilizing the exoscope for anterior cervical spine procedures allows surgeons to spend less time in a deviated posture., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To evaluate mydriatic handheld retinal imaging performance assessed by point-of-care (POC) artificial intelligence (AI) as compared with retinal image graders at a centralized reading center (RC) in identifying diabetic retinopathy (DR) and diabetic macular edema (DME)., Design: Prospective, comparative study., Subjects: Five thousand five hundred eighty-five eyes from 2793 adult patients with diabetes., Methods: Point-of-care AI assessment of disc and macular handheld retinal images was compared with RC evaluation of validated 5-field handheld retinal images (disc, macula, superior, inferior, and temporal) in identifying referable DR (refDR; defined as moderate nonproliferative DR [NPDR], or worse, or any level of DME) and vision-threatening DR (vtDR; defined as severe NPDR or worse, or any level of center-involving DME [ciDME]). Reading center evaluation of the 5-field images followed the international DR/DME classification. Sensitivity (SN) and specificity (SP) for ungradable images, refDR, and vtDR were calculated., Main Outcome Measures: Agreement for DR and DME; SN and SP for refDR, vtDR, and ungradable images., Results: Diabetic retinopathy severity by RC evaluation: no DR, 67.3%; mild NPDR, 9.7%; moderate NPDR, 8.6%; severe NPDR, 4.8%; proliferative DR, 3.8%; and ungradable, 5.8%. Diabetic macular edema severity by RC evaluation was as follows: no DME (80.4%), non-ciDME (7.7%), ciDME (4.4%), and ungradable (7.5%). Referable DR was present in 25.3% and vtDR was present in 17.5% of eyes. Images were ungradable for DR or DME in 7.5% by RC evaluation and 15.4% by AI. There was substantial agreement between AI and RC for refDR (κ = 0.66) and moderate agreement for vtDR (κ = 0.54). The SN/SP of AI grading compared with RC evaluation was 0.86/0.86 for refDR and 0.92/0.80 for vtDR., Conclusions: This study demonstrates that POC AI following a defined handheld retinal imaging protocol at the time of imaging has SN and SP for refDR that meets the current United States Food and Drug Administration thresholds of 85% and 82.5%, but not for vtDR. Integrating AI at the POC could substantially reduce centralized RC burden and speed information delivery to the patient, allowing more prompt eye care referral., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2023 by the American Academy of Ophthalmology.)

Objective: To determine the influence of extreme brachycephalic conformation on presenting signs, imaging findings, intraoperative and perioperative complications following total ear canal ablation and lateral bulla osteotomy (TECA-LBO)., Study Design: Cross-sectional retrospective study., Animals: A total of 306 (n = 242 dogs) TECA-LBOs (extreme brachycephalic breeds [EBB] = 81, other breeds [OB] = 225)., Methods: Medical records of patients undergoing TECA-LBO at a single referral institution (2010-2022) were evaluated., Results: Extreme brachycephalic breeds most commonly presented acutely, at a younger age with oto-neurological signs (46/81, 56.8%). Chronic otitis externa without neurological signs (171/225, 76.0%) was most common in OBs. Extreme brachycephalic breeds preoperatively presented more frequently with facial nerve paresis (p = .001), vestibular syndrome (p = .001), and Horner's syndrome (p = .002) compared to OBs. On diagnostic imaging, bilateral changes (p = .038), aural masses (p = .045), para-aural abscesses (p = .011), otitis interna (p = .001), and brainstem changes (p = .001) were more common in EBBs. The apparent difference in intraoperative complication rate between EBBs (9/81, 11.1%) and OBs (12/225, 5.3%) did not reach statistical significance (p = .078). Perioperative complications occurred in 85/306 (27.8%) of TECA-LBOs with no difference in perioperative complication rate between EBBs (19/81, 23.5%) and OBs (66/225, 29.3%) (p = .586)., Conclusion: Extreme brachycephalic breeds are more likely to present for TECA-LBO acutely, with neurological signs and more advanced diagnostic imaging abnormalities. Intra- and perioperative complication rates did not differ between EBBs and OBs., Clinical Significance: Despite being subjectively more technically challenging, TECA-LBO did not result in more surgical complications in EBBs. Reported data are useful for effectively informing clients of the specific risks of TECA-LBO surgery., (© 2023 The Authors. Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Objective: To describe and evaluate the steps required to perform a combined endoscopic endonasal/transoral transclival transodontoid approach for anterior decompression of the craniovertebral junction., Methods: The endoscopic endonasal transclival transodontoid approach combined with endoscopic transoral decompression was performed on 4 cadaveric specimens. Evaluation of this combined technique; a review of the literature; and the nuances, advantages, and pitfalls are reported., Results: Adequate wide anterior decompression was achieved in all specimens. This combined approach allowed the preservation of the anterior arch of C1 without injuring the eustachian tube anatomy and avoiding internal carotid artery manipulation., Conclusions: Mastery of both techniques allows for a safe and comfortable surgical corridor. The transoral and transnasal approaches should not be considered as either/or techniques, but rather as a complement to each other. However, as with all new or developing techniques, there is a steep learning curve, which requires ample training in the skull base laboratory., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Chiari I malformation results from a mismatch between the posterior fossa bones and neural components. Management usually relies on surgical treatment. Despite being the most common assumed positioning, the prone position can be challenging in high body mass index (BMI) patients (>40 kg/m 2 )., Methods: Between February 2020 and September 2021, 4 consecutive patients with class III obesity underwent posterior fossa decompression. The authors describe nuances of the positioning and perioperative details., Results: No perioperative complications were reported. These patients are at a lower risk of bleeding and increased intracranial pressure as a consequence of low intra-abdominal pressure and venous return. In this context, the semi-sitting position, with the aid of accurate monitoring for venous air embolism, seems to be an advantageous surgical position in this group of patients., Conclusions: We present our results and technical nuances on positioning high BMI patients for posterior fossa decompression using a semi-sitting position., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background  Advances in skull base surgery have increased the need for a detailed understanding of skull base anatomy and its intrinsic relationship to surrounding structures. This has resulted in an improvement in patient outcomes. The frontotemporal orbitozygomatic (FTOZ) transcavernous approach (TCA) is an excellent option for treating complex lesions involving multiple compartments of the skull base, including the sellar and parasellar, third ventricle, orbit, and petroclival region. Objective  This article aimed to provide a detailed cadaveric dissection accompanying a thorough procedure description, including some tips and pitfalls of this technique. Methods  Microsurgical dissection was performed in four freshly injected cadaver heads at the Cranial Base Neuroanatomy Laboratory, Cleveland Clinic Florida. The FTOZ TCA was performed on both sides of the four specimens. The advantages and disadvantages were discussed based on the anatomic nuances of this approach. Results  The FTOZ TCA represented a wide access to the anterior, middle, and posterior fossa. When combined with an anterior clinoidectomy, it allowed for significant and safe internal carotid artery mobilization. This approach created numerous windows, including opticocarotid, carotid-oculomotor, supratrochlear, infratrochlear, anteromedial, anterolateral, and posteromedial triangles. The only drawback was the length of the dissection and the level of surgical acumen required to perform it. Conclusion  Despite its technical difficulty, the FTOZ TCA should be considered for the surgical management of basilar apex aneurysms and tumors surrounding the cavernous sinus, sellar/parasellar, retrochiasmatic, and petroclival region. Continuous training and dedicated time in the skull base laboratory can help achieve the necessary skills required to perform this approach., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: The neurosurgical management of idiopathic intracranial hypertension (IIH) remains controversial. Although shunting and newer endovascular stenting techniques are part of the neurosurgical armamentarium to treat medically refractory IIH symptoms, optic nerve sheath fenestration has traditionally been performed by ophthalmologists., Objective: We present a detailed cadaveric dissection that simulates the endoscopic endonasal optic nerve sheath decompression (EONSD) technique along with the literature review., Methods: EONSD was performed in four freshly injected cadaveric specimens. Additionally, a systematic review from different electronic databases has been done., Results: Bilateral EONSD was performed in all specimens without significant technical difficulties. Based on our experience, there is no need to expose the periorbita or orbital apex. The primary anatomic landmarks were the optic canal, the lateral opticocarotid recess, the tuberculum, the limbus, and the clinoid segment of the internal carotid artery. Based on the systematic review, 68 patients (77.9% female) underwent EONSD, with a mean age of 33.4 ± 6.9 years in adult patients. Follow-up ranged from 3 to 58 months across different studies. The pooled meta-analysis showed headache, papilledema, and visual disturbance improvement in 78% [95%CI 0.65-0.90], 72% [95%CI 0.61-0.83], and 88% [95%CI 0.80-0.96] of cases who underwent EONSD, respectively. The subgroup analysis showed there was no statistically significant difference between unilateral and bilateral EONSD in terms of different measured outcomes., Conclusion: EONSD is a feasible surgical procedure that may obviate the need for shunting in patients with IIH. Although clinical studies showed that EONSD is a safe and effective technique, further studies are required to establish the preferences of either unilateral or bilateral approaches., Competing Interests: Declaration of Competing Interest The authors declare that the article content was composed in the absence of any commercial, or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Glioblastoma (GBM) patients have a 20-30 incidence of venous thromboembolic events. EGFR is a widely used prognostic marker for many cancers. Recent lung cancer studies have described relationships between EGFR amplification and an increased incidence of thromboembolic complications. We aim to explore this relationship in glioblastoma patients. Methods : Two hundred ninety-three consecutive patients with IDH wild-type GBM were included in the analysis. The amplification status of EGFR was measured using fluorescence in situ hybridization (FISH). Centromere 7 (CEP7) expression was recorded to calculate the EGFR-to-CEP7 ratio. All data were collected retrospectively through chart review. Molecular data were obtained through the surgical pathology report at the time of biopsy. Results: There were 112 subjects who were EGFR-amplified (38.2%) and 181 who were non-amplified (61.8%). EGFR amplification status was not significantly correlated with VTE risk overall ( p = 0.2001). There was no statistically significant association between VTE and EGFR status after controlling for Bevacizumab therapy ( p = 0.1626). EGFR non-amplified status was associated with an increased VTE risk in subjects greater than 60 years of age ( p = 0.048). Conclusions : There was no significant difference in occurrence of VTE in patients with glioblastoma, regardless of EGFR amplification status. Patients older than 60 years of age with EGFR amplification experienced a lower rate of VTE, contrary to some reports on non-small-cell lung cancer linking EGFR amplification to VTE risk.

Introduction: The purpose of this study was to compare 2-field (2F) and 5-field (5F) mydriatic handheld retinal imaging for the assessment of diabetic retinopathy (DR) severity in a community-based DR screening program (DRSP)., Methods: This was a prospective, cross-sectional diagnostic study, evaluating images of 805 eyes from 407 consecutive patients with diabetes acquired from a community-based DRSP. Mydriatic standardized 5F imaging (macula, disc, superior, inferior, temporal) with handheld retinal camera was performed. 2F (disc, macula), and 5F images were independently assessed using the International DR classification at a centralized reading center. Simple (K) and weighted (Kw) kappa statistics were calculated for DR. Sensitivity and specificity for referable DR ([refDR] moderate nonproliferative DR [NPDR] or worse) and vision-threatening DR ([vtDR] severe NPDR or worse) for 2F compared to 5F imaging were calculated., Results: Distribution of DR severity by 2F/5F images (%): no DR 66.0/61.7, mild NPDR 10.7/14.4, moderate NPDR 7.9/8.1, severe NPDR 3.3/5.6, proliferative DR 5.6/4.6, ungradable 6.5/5.6. Exact agreement of DR grading between 2F and 5F was 81.7%, within 1-step 97.1% (K = 0.64, Kw = 0.78). Sensitivity/specificity for 2F compared 5F was refDR 0.80/0.97, vtDR 0.73/0.98. The ungradable images rate with 2F was 16.1% higher than with 5F (6.5 vs. 5.6%, p &lt; 0.001)., Conclusions: Mydriatic 2F and 5F handheld imaging have substantial agreement in assessing severity of DR. However, the use of mydriatic 2F handheld imaging only meets the minimum standards for sensitivity and specificity for refDR but not for vtDR. When using handheld cameras, the addition of peripheral fields in 5F imaging further refines the referral approach by decreasing ungradable rate and increasing sensitivity for vtDR., (© 2023 S. Karger AG, Basel.)

The objective of this retrospective case series was to report overall peri-operative complications, short- to mid-term outcome, and owner satisfaction of closing tibial wedge osteotomy (CTWO) using locking compression plates, in dogs weighing ≤ 20 kg, for the treatment of cranial cruciate ligament disease. Medical records from 2015 to 2020 were reviewed for surgical technique, intraoperative findings, and complications. Pre- and postoperative radiographs were evaluated for healing, complications, and tibial plateau angles (TPAs). A follow-up telephone questionnaire was used to evaluate patient outcome and owner satisfaction. Eighty-one client-owned dogs (12.0 kg ± 3.0 kg; 95% CI: 8.4 to 15.5) (N = 89 stifles) were included in the study. Mean tibial plateau angles at preoperative, postoperative, and 8-week follow-up were 29.7° ± 4.1° (95% CI: 25.5 to 33.8), 6.7° ± 2.6° (95% CI: 4.2 to 9.2), and 7.8° ± 2.4° (95% CI: 4.9 to 10.6), respectively. Tibial plateau angles had significantly increased at the 8-week follow-up assessment by 1.04° ± 1.8°; 95% CI: -0.8 to -2.8) compared to immediately postoperative. The postoperative complication rate was 4.49% (4 cases). Overall satisfaction was excellent with good return to limb function. Closing tibial wedge osteotomy can be performed in dogs ≤ 20 kg, using locking compression plates, achieving excellent overall owner satisfaction and return to function., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Central to the impacts of CD4 T cells, both positive in settings of infectious disease and cancer and negative in the settings of autoimmunity and allergy, is their ability to differentiate into distinct effector subsets with specialized functions. The programming required to support such responses is largely dictated by lineage-specifying transcription factors, often called 'master regulators'. However, it is increasingly clear that many aspects of CD4 T cell immunobiology that can determine the outcomes of disease states involve a broader transcriptional network. Eomesodermin (Eomes) is emerging as an important member of this class of transcription factors. While best studied in CD8 T cells and NK cells, an increasing body of work has focused on impacts of Eomes expression in CD4 T cell responses in an array of different settings. Here, we focus on the varied impacts reported in these studies that, together, indicate the potential of targeting Eomes expression in CD4 T cells as a strategy to improve a variety of clinical outcomes.

Introduction: Resection of intra-axial tumors (IaT) in eloquent brain regions risks major postoperative neurological deficits. Awake craniotomy is often used to navigate these areas; however, some patients are ineligible for awake procedures. The trans-sulcal approach (TScal) was introduced to reduce parenchymal trauma during tumor resection. We report our experiences utilizing TScal for resection of deep IaT located in eloquent areas. Materials and Methods: This is a single-center retrospective analysis of patients who underwent IaT resection in eloquent areas via TScal from January 2013 to April 2021. Seventeen cases were reviewed, and relevant data was collected. Fluorescence-guided surgery with 5-aminolevulinic acid (ALA) and intraoperative ultrasound was performed in some cases. Results: Seventeen patients (10 males, 7 females) averaging 61.2 years-old (range, 21-76) were included in this study. Average length of stay was 4.8 days, and only 2 patients (11.8%) required hospital readmission within 30 days. Gross total resection (GTR) was achieved in 15 patients (88.2%), while subtotal resection occurred in 2 patients (11.8%). Eleven patients (64.7%) reported full resolution of symptoms, 4 patients (23.5%) reported deficit improvement, and 2 patients (11.8%) experienced no change from their preoperative deficits. No patient developed new permanent deficits postoperatively. Discussion: GTR, preoperative deficit reduction, and complications were comparable to awake craniotomy and other TScal studies. Ancillary intraoperative techniques, such as brain mapping, 5-ALA and intraoperative ultrasound, are afforded by TScal to improve resection rates and overall outcomes. Conclusions: TScal can be an option for patients with deep lesions in eloquent areas who are not candidates for awake surgeries.

Aim: To come up with a newly developed survey tool that will measure the students' level of quality in writing nursing care plans (NCPs)., Background: Exploring various challenges of students in writing NCP would enlighten educators to design innovative strategies on how to mitigate gaps between nursing education and practice., Methods: This study utilized an exploratory sequential mixed-methods design in three stages. In phase 1, qualitative semi-structured interviews of 22 students were conducted, and the data were analysed using the Colaizzi method. In phase 2, qualitative results were transformed into survey components, constructs and items, and the data were developed into a new survey tool based on the nursing process system (NPS) model. In phase 3, a quantitative cross-sectional survey of 195 nursing students was conducted to measure their level of quality in writing NCP, and the data were analysed using descriptive statistics of the SPSS software., Results: In the first (qualitative) phase, five themes emerged from various challenges of nursing students in writing care plans: (a) data gathering; (b) identifying clients' problems; (c) formulating sustainable goals; (d) providing appropriate interventions; and (5) recognizing client's outcomes. In the second phase, a valid and reliable tool called the Student Survey on Writing Nursing Care Plan (SSW-NCP) was developed and tested. Lastly, in the third (quantitative) phase, the nursing students have shown a 'very good' level of quality in writing NCP., Conclusion: Determining students' level of quality in writing NCP would come up with comprehensive ways of improving student competencies in patient care management., Implications for Nursing Management: The survey tool that is formulated from the study will provide relevant information for nurse educators and managers in managing students' and registered nurses' capabilities in writing an excellent care plan., (© 2020 John Wiley & Sons Ltd.)

Objectives: To characterize primary care providers' (PCPs) practice patterns for atopic dermatitis (AD) in children <2 years old and determine the need for AD guidelines for PCPs focused on this age group., Study Design: This is a mixed-methods study consisting of a survey and a retrospective medical record review of PCP practices in the Chicago metropolitan area. The survey was analyzed using both quantitative and qualitative methods., Results: In the survey (n = 52 respondents), PCPs reported management of AD is different in children <2 years compared with older children (88%). They were more likely to refer to a specialist (65%) and less likely to use high-potency topical corticosteroids (64%). In the chart review, PCP visits for children 2-5 years old (n = 50 914) vs those <2 years old (n = 71 913) for AD, older children had medium- and high-potency topical corticosteroids prescribed more frequently than younger children (0.66% vs 0.37%, P < .01 and .15% vs 0.05%, P < .01, respectively). In the subset of children <2 years of age who also were evaluated by a specialist (n = 109), medium- and high-potency topical corticosteroids were prescribed disproportionately at visits to providers in dermatology (57%) vs allergy (30%) vs pediatrics (15%) (P < .01). PCPs suggested that guidelines for this age group should include recommendations for preferred corticosteroids (39%), allergy management (35%), referral criteria (22%), and assessment of disease severity (11%)., Conclusions: PCP management of AD in children <2 years is different from older children, with possible underuse of medium/high-potency topical corticosteroids. Clear guidelines for this age group are needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Emergency physicians are trained in urgent fracture reduction. Many hospitals lack readily available in-house orthopedic coverage., Objectives: The aim of this study was to determine success rates for reduction of pediatric distal radius or ulna fractures by emergency department (ED) physicians., Methods: We conducted a retrospective study of children younger than 18 years presenting to a large, urban, freestanding children's hospital from January 1, 2009, to December 31, 2010, with forearm fracture. Exclusions included open fracture, those requiring immediate surgical intervention, or additional fractures. The primary end point was the proportion of successful closed forearm fracture reductions in the ED, as defined by orthopedic follow-up., Results: All reductions were performed by a board-certified/eligible pediatric emergency medicine (PEM) physician or PEM fellow. Two hundred ninety-five fractures were reduced in the ED during the study period. Mean age was 8.27 years (median, 8 years; range, 1-16 years), and males comprised 69.2% (n = 204). A total of 222 fractures (76%) were of the distal forearm, and 70 involved the midshaft (24%). Orthopedic follow-up was completed in 77.3%. A total of 33 patients (11%) required remanipulation; 24 in the distal forearm fracture group (22 closed reductions, 2 open reductions with internal fixation) versus 9 in the midshaft group (7 closed reductions, 2 open reductions with internal fixation) (P = 0.948)., Conclusions: The literature reveals 7% to 39% of children with fracture reductions performed in the ED by orthopedic surgeons/residents require remanipulation. Our rate of 11% is consistent within that range. With training, PEM physicians have similar success rates as orthopedists in forearm fracture reductions.

Objectives: To assess the breed-specific prevalence of, and effects of corrective airway surgery on, gastrointestinal signs in French bulldogs, English bulldogs and pugs presenting with brachycephalic airway syndrome to a referral teaching hospital., Materials and Methods: In this retrospective study, ptyalism, regurgitation and vomiting were graded at presentation using a previously established scoring system. Staphylectomy and nares resection were performed on all dogs. Gastrointestinal signs were re-assessed via telephone follow-up at least 6 weeks after surgery., Results: Ninety-eight dogs were included: French bulldogs (n=43), English bulldogs (n=12) and pugs (n=43). Overall population prevalence of all gastrointestinal signs was 56%. Breed-specific prevalence for French bulldogs was 93%, English bulldogs 58% and pugs 16%. There was post-surgical clinical improvement in gastrointestinal signs for the whole study population, especially in French bulldogs., Clinical Significance: The prevalence of gastrointestinal signs in dogs presenting with brachycephalic airway syndrome and improvement in these clinical signs following corrective surgery may vary between breeds., (© 2018 British Small Animal Veterinary Association.)

Synthetic cannabinoids (SC), are a novel class of designer drugs which emerged as a drug of abuse in the late 2000's. We report a case series of 6 patients who may have smoked a synthetic cannabinoid product in a remote wilderness setting. They presented with varying degrees of altered mental status, agitation, and seizures. Two were confirmed to have AB-PINACA, ADB-PINACA and their respective pentanoic acid metabolites in biological specimens via liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS). Both compounds had DEA Schedule I classification at the time of case presentation, and 22 SCs are currently temporary or permanent DEA Schedule I. More than 150 SCs are known to date, and new compounds are appearing at a rapid rate on darknet and surface web e-commerce websites, marketed as "research chemicals" or "legal highs." The scale and rapidity of SC evolution make legal control and analytical detection difficult. Nontargeted testing with liquid chromatography high resolution mass spectrometry (LC-HRMS), examining both parent compounds and metabolites, is the ideal method for novel SC identification and confirmation. Due to full agonism at the cannabinoid receptors CB1 and CB2, clinical effects are more severe than marijuana, which is a partial cannabinoid receptor agonist. They include agitated delirium, lethargy and coma, seizures, tachycardia, hypertension, and hallucinations, among other findings. Treatment is primarily symptomatic and aimed at airway protection and control of agitation and seizures. SCs do not appear to be abating anytime soon and require the cooperation of law enforcement, analytical scientists, and clinicians to adequately control. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.', (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate the effect of sacculectomy on the immediate postoperative complication rate in dogs affected with brachycephalic obstructive airway syndrome., Materials and Methods: Retrospective review of clinical records of brachycephalic dogs with everted saccules that underwent surgery for brachycephalic obstructive airway syndrome between 2009 and 2014. Dogs were grouped as those having nares resection and staphylectomy only and those having nares resection, staphylectomy and laryngeal sacculectomy. Complications were scored as mild, moderate or severe., Results: In total, 37 dogs were included in the sacculectomy group and 44 in the comparator group. Dogs that had undergone sacculectomy were more likely to develop postoperative complications, with 18 of 37 developing complications, nine of which were moderate to severe. In the group without sacculectomy, nine of 44 dogs developed complications, of which one was severe. Different breed distribution between groups might also impact this outcome., Clinical Significance: The results suggest that sacculectomy might increase morbidity following brachycephalic airway surgery, but repeat studies are required to confirm this result. Further information is also required to determine whether the short-term risks of sacculectomy are outweighed by superior long-term functional outcome., (© 2017 British Small Animal Veterinary Association.)

Time-resolvable quantitative measurements of polymer concentration are very useful to elucidate protein polymerization pathways. There are numerous techniques to measure polymer concentrations in purified protein solutions, but few are applicable in vivo. Here we develop a methodology combining microscopy and spectroscopy to overcome the limitations of both approaches for measuring polymer concentration in cells and cell extracts. This technique is based on quantifying the relationship between microscopy and spectroscopy measurements at many locations. We apply this methodology to measure microtubule assembly in tissue culture cells and Xenopus egg extracts using two-photon microscopy with FLIM measurements of FRET. We find that the relationship between FRET and two-photon intensity quantitatively agrees with predictions. Furthermore, FRET and intensity measurements change as expected with changes in acquisition time, labeling ratios, and polymer concentration. Taken together, these results demonstrate that this approach can quantitatively measure microtubule assembly in complex environments. This methodology should be broadly useful for studying microtubule nucleation and assembly pathways of other polymers., (© 2017 Kaye et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

FRET measurements can provide dynamic spatial information on length scales smaller than the diffraction limit of light. Several methods exist to measure FRET between fluorophores, including Fluorescence Lifetime Imaging Microscopy (FLIM), which relies on the reduction of fluorescence lifetime when a fluorophore is undergoing FRET. FLIM measurements take the form of histograms of photon arrival times, containing contributions from a mixed population of fluorophores both undergoing and not undergoing FRET, with the measured distribution being a mixture of exponentials of different lifetimes. Here, we present an analysis method based on Bayesian inference that rigorously takes into account several experimental complications. We test the precision and accuracy of our analysis on controlled experimental data and verify that we can faithfully extract model parameters, both in the low-photon and low-fraction regimes., Competing Interests: TYY was supported in part by the Samsung scholarship (https://www.ssscholarship.com/community/HomeEn.screen). This does not alter our adherence to PLOS ONE policies on sharing data and materials, and Samsung had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background: Tricuspid annular plane systolic excursion (TAPSE) is a useful estimate of right ventricular function in humans. Reference intervals for dogs have been generated, but the value of measuring TAPSE in other diseases, or investigating the association between TAPSE and outcome, is unknown., Hypothesis: TAPSE is lower in Boxer dogs with ≥50 VPCs/24 h on Holter than in dogs with fewer ventricular ectopics, and lower TAPSE is associated with a shorter survival time., Animals: Fifty Boxer dogs that presented for investigation of syncope or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) at a veterinary teaching hospital (2004-2011)., Methods: Retrospective study. Clinical records, Holter, and echocardiographic data were reviewed. TAPSE was measured in a blinded manner on stored echocardiographic cine-loops using anatomic M-mode. Outcome information was obtained and death was classified as cardiac or noncardiac. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards models., Results: TAPSE was lower in Boxers with ≥50 VPCs/24 h (13.9 ± 4.04 mm) than Boxers with <50 VPCs/24 h (16.8 ± 3.21 mm; P < .001). TAPSE <15.1 mm was associated with shorter cardiac survival time in all dogs (P = .004) and also in dogs without left ventricular dysfunction (P = .035). When controlling for other variables, including ventricular tachycardia on Holter and left ventricular systolic dysfunction, multivariable analysis showed that TAPSE remained an independent predictor of time to cardiac death (HR >4.09, 95%CI 1.15-16.9, P < .029)., Conclusions and Clinical Importance: TAPSE offers prognostic value for Boxer dogs, including those with apparently normal systolic function and ≥50 VPCs/24 h on Holter analysis., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objectives: The outcome in dogs with pulmonary hypertension associated with natural Angiostrongylus vasorum infection is unclear. This study aimed to report long-term outcome of dogs with A. vasorum and pulmonary hypertension, and to evaluate factors associated with pulmonary hypertension development. It was hypothesised that dogs with pulmonary hypertension had a shorter survival time than dogs without pulmonary hypertension., Methods: Retrospective review of clinical records of dogs diagnosed with A. vasorum. Dogs were classified as having or not having pulmonary hypertension based on clinical signs and imaging findings. Signalment, signs and outcome were recorded. DNA obtained from banked samples was genotyped for the PDE5a:E90K polymorphism, a possible factor in development of pulmonary hypertension., Results: The proportion of dogs with moderate-to-severe pulmonary hypertension and A. vasorum infection in the study population was 14 · 6%. No difference in the population characteristics or PDE5a genotype was detected between dogs with and without pulmonary hypertension. Dogs with pulmonary hypertension had a significantly shorter survival time (P = 0 · 006) and a greater risk of death within 6 months of diagnosis (odds ratio 12 · 5, 95% confidence interval 2 · 1 to 74 · 9; P = 0 · 0053)., Clinical Significance: A. vasorum-associated pulmonary hypertension is an important problem in naturally infected dogs and has a negative effect upon survival., (© 2014 British Small Animal Veterinary Association.)

Snail bait poisoning is rare in horses. Cases have been reported, but clinical signs and subsequent prognostic indicators have been poorly documented and must be extrapolated from cases in companion animals. We describe in detail the poisoning of a horse that consumed a lethal dose of the carbamate, methiocarb. There are currently no guidelines for treating equine methiocarb toxicoses, but the principles of management are based on supportive therapy., (© 2012 The Authors. Australian Veterinary Journal © 2012 Australian Veterinary Association.)

Dense mammographic patterns are a strong predictor of breast cancer risk. Factors at differing stages of life have been linked to breast cancer risk, although rarely studied simultaneously. We aimed to investigate whether birth weight and factors later in life were associated with mammographic density in the Newcastle Thousand Families Study. The Study originally consisted of all 1142 babies born in May and June 1947 to mothers resident in Newcastle upon Tyne in Northern England. Detailed information was collected prospectively during childhood, including birth weight and socio-economic circumstances. At age 49-51 years, 574 study members completed a 'Health and Lifestyle' questionnaire. Of the 307 surviving women who returned these questionnaires, 199 returned a further questionnaire asking for details of routine mammographic screening, their reproductive and contraceptive history. Mammographic patterns were coded into Wolfe categories. This was analysed, by ordinal logistic regression, in relation to a range of variables at different stages of life. Increased standardised birth weight (odds ratio, OR 1.32 (95% CI 1.02-1.71) P = 0.03) was a significant independent predictor of higher density. Increasing body mass index (BMI) was predictive of lower density (OR 0.86 per Kg/m(2) (95% CI 0.81-0.92) P < 0.001), as was having reached menopause (OR, compared to pre- and peri-menopausal, 0.41 (95% CI 0.23-0.73) P = 0.002). Interactions were seen between menopausal status and both BMI and age at menarche (P = 0.06) on density, although for neither did the direction of association change. After adjustment for factors acting throughout life, we identified a significant association between standardised birth weight and density in adulthood, consistent with previous research suggesting that heavier babies have an increased risk of breast cancer in later life. We also confirmed associations between both BMI and menopausal status.

We present data on the design and performance analysis of phase shifted distributed feedback (DFB) lasers on the hybrid silicon platform. The lasing wavelength for various input currents and temperatures, for devices with standard quarter-wavelength, 60 μm and 120 μm-long phase shift are compared for mode stability and output power. The pros and cons of including a large phase shift region in the grating design are analyzed., (© 2011 Optical Society of America)

Arterial aneurysms are defined as localized abnormal dilatations in an arterial wall. We report the first case of multiple true aneurysms in the female breast in a patient with a history of chronic amphetamine abuse who presented with a probable subarachnoid haemorrhage (SAH).

The World Health Organization (WHO) and other organizations report that the prevalence of human diseases during the past decade is rapidly increasing. Population growth and the pollution of water, air, and soil are contributing to the increasing number of human diseases worldwide. Currently an estimated 40% of world deaths are due to environmental degradation. The ecology of increasing diseases has complex factors of environmental degradation, population growth, and the current malnutrition of about 3.7 billion people in the world., (© Springer Science+Business Media, LLC 2007.)

In a recent study of rhytidectomy patients, the most common complications were hematoma, inflammation, crusting, hypertrophic scars, hair loss, and changes in ear lobe appearance. The nurse's role in early detection and prevention cannot be overlooked. This article will review these complications and less common ones, emphasizing the known etiologies, signs and symptoms, and the nurse's role in assessment and intervention.

Sampatrilat is a dual inhibitor of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) under development for the treatment of hypertension and congestive heart failure. In order to support the early clinical development (with oral administration and an expected low bioavailability), a sensitive and selective assay was required. A method for plasma was developed and validated employing HPLC APCI MS-MS. The plasma samples were extracted on solid-phase extraction cartridges, derivatised with BF3-methanol, diluted, extracted again and then subjected to HPLC APCI-MS-MS. Derivatisation was necessary because the two carboxyl group in the molecule prevented efficient ionisation in the heated nebuliser source. The calibration range was from 0.5 to 20 ng ml(-1) and the lower limit of quantification was 0.5 ng ml(-1). Imprecision and inaccuracy were determined on three separate occasions at three concentrations (0.5, 5 and 20 ng ml[-1]) and shown to be lower than 10% in every case.

Sampatrilat is a dual inhibitor of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) under development for the treatment of hypertension and congestive heart failure. In order to support the early clinical development (with oral administration and an expected low bioavailability), a sensitive and selective assay was required. An HPLC-atmospheric-pressure chemical ionisation mass-spectrometric (HPLC-APCI-MS-MS) assay had been already validated (R.F. Venn et al., J. Pharm. Biomed. Anal., in press), but due to its low throughput an alternative method was sought. As the molecule is peptide-like and not metabolised, we believed the immunoassay approach was appropriate. Thus we developed an immunoassay for the compound using time-resolved fluorescence as an end-point (DELFIA) with lower limits of quantification of 0.2 ng ml(-1) for the plasma assay and 5 ng ml(-1) for the assay in urine. This assay is a 96-well plate based competitive immunoassay; the end-point is the determination of a (non-radioactive) europium label by time-resolved fluorimetry. Sampatrilat is labelled with chelated europium via isothiocyanate chemistry. The advantage of this assay is its extremely high throughput, allowing rapid analysis of many thousands of samples. The DELFIA method was successfully cross-validated with the HPLC-APCI-MS-MS method.

1. Candoxatrilat, an active neutral endopeptidase inhibitor, was released rapidly from the inactive prodrug candoxatril in vivo in mouse, rat, rabbit, dog and man. 2. Oral doses of [14C]-candoxatril were cleared rapidly, mostly by ester hydrolysis to candoxatrilat, in mouse, dog and man. A complementary intravenous study in man with [14C]-candoxatrilat showed that the active drug was virtually completely renally cleared. Neither candoxatril nor candoxatrilat underwent chiral inversion in man. 3. Systemic availability of candoxatrilat from the oral prodrug was estimated to be 88, 53, 42, 17 and 32% in mouse, rat, rabbit, dog and man respectively. Plasma clearance of candoxatril was too rapid to enable pharmacokinetic parameter calculation in mouse and rabbit; for man, the apparent oral clearance was 57.9 ml/min/kg and the elimination half-life was 0.46 h. 4. For intravenous candoxatrilat, total plasma clearance values were 32, 15, 5.5, 5.8 and 1.9 ml/min/kg for mouse, rat, rabbit, dog and man respectively. Renal clearance values were 8.7, 7.2, 2.9 and 1.7 ml/min/kg for mouse, rat, dog and man and these approximate to the respective glomerular filtration rates. Allometric scaling with respect to bodyweight across the species allowed reasonable prediction of the above two clearance parameters in man.

A novel method has been developed for the rapid solid phase extraction of drugs and metabolites from biological fluids, prior to further analysis. The newly designed, 96-tube micropreparation block facilitates high throughput by enabling the extraction of 96 samples simultaneously. The system is described, linked to HPLC/APCI-MS/MS, for the determination of darifenacin in human plasma. The resulting procedure, using deuterated darifenacin as internal standard, is validated over the concentration range 25-2000 pg/mliter; accuracy (0.6-4.6%) and precision (3.6-18.8%) are considered acceptable and overall recovery was determined to be approximately 50%.

Biopsy of the impalpable breast lesion is an increasing part of the surgical workload as a result of the National Breast Cancer Screening Programme. A specimen mount card has been described to orientate such specimens in three dimensions prior to radiological and pathological examination. Experience with 243 biopsies in this unit has shown it to be a useful aid in determining completeness of excision. It may also be used as a guide to further surgery when excision is incomplete and breast conservation is the treatment option of choice.

Purpose: We assessed the outcome of 31 patients with severe neuropsychiatric (NP) systemic lupus erythematosus (NPSLE) treated with intravenous cyclophosphamide (IV-CYC), and identified clinical predictors of response to therapy., Methods: The authors performed a retrospective chart review and classified patients by NP manifestation and response to therapy as measured by serial anatomic imaging and neurodiagnostic studies coupled with clinical assessment of improvement., Results: Neuropsychiatric manifestations occurred with the following frequencies: organic brain syndromes (OBS) 55%, stroke syndromes 35%, peripheral or mononeuropathy 32%, seizures 29%, psychiatric symptoms 26%, transverse myelitis 16%, cranial neuropathies 13%, other 16%. Most patients had multiple NP manifestations, with a median of two. Ninety percent of patients had failed therapy with corticosteroids with or without cytotoxic drugs prior to treatment with IV-CYC. Eight patients received synchronous plasmapheresis along with IV-CYC. After treatment with IV-CYC, NP deficits substantially improved in 61% (group I), stabilized in 29% (group S), and progressively deteriorated in 10% (group P). Patients in group I had significantly fewer NP manifestations than combined group S+P, two versus four, and a lower frequency of OBS, 37% versus 83%., Conclusion: Intravenous cyclophosphamide appears to be an effective treatment for some patients with severe NPSLE refractory to other forms of therapy. Higher number of NP manifestations and presence of OBS may predict poor outcome and identify a group of patients for whom early aggressive therapy may be indicated.

A total of 112 women was entered into a randomised study to investigate the effects of suction drainage on haematoma formation in breast biopsy wounds. Of 107 evaluable patients, 52 received drainage and 55 had no drain. The wounds were examined 1 week after operation when the volume of wound haematoma was measured using ultrasonography. Haematomas were present in 48 (87%) patients with undrained wounds compared with 34 (65%) patients with drained wounds (P = 0.014, chi 2 test). Median haematoma volume was 20 ml (range 0-172.5 ml) in the undrained group compared with 2 ml (range 0-100 ml) in the drained group (P = 0.001, Mann-Whitney U test). There was one wound infection in each group. There was no difference in median pain score or duration of pain between the groups. While suction drainage significantly reduces the incidence and volume of wound haematomas, this does not appear to influence outcome.

Doramectin, 25-cyclohexyl-5-O-demethyl-25-de(l-methylpropyl)avermectin A1a, was selected as the best of a series of novel avermectins prepared by mutational biosynthesis. The primary evaluation of its in vivo antiparasitic activity was carried out using a rat Trichostrongylus colubriformis model and a rabbit Psoroptes cuniculi model. In each case the new avermectin performed favourably relative to dihydroavermectin B1a (DHAVM), the major component of ivermectin. Doramectin was extensively evaluated in cattle using an experimental micelle formulation, proving highly effective in cattle infected with Ostertagia ostertagi, Cooperia oncophora and Dictyocaulus viviparus when administered subcutaneously at 200 micrograms kg-1. The plasma pharmacokinetic characteristics of doramectin in cattle following intravenous administration revealed a plasma half-life of approximately 89 h. In the micelle formulation, doramectin administered subcutaneously at 400 micrograms kg-1 provided persistent activity against infection of cattle with C. oncophora and O. ostertagi for at least 8 and 12 days respectively.

The pharmacokinetics of doramectin, a novel avermectin, were evaluated following parenteral administration in a range of oil-based formulations in an attempt to optimise the formulation. Therapeutic and persistent efficacies against Cooperia oncophora were also evaluated. This approach led to the identification of formulations based upon sesame oil and ethyl oleate which gave more prolonged doramectin plasma concentrations with no loss in therapeutic efficacy and improved persistent efficacy following subcutaneous administration to cattle at a dosage of 200 micrograms kg-1. The importance of using both pharmacokinetic and efficacy end points to distinguish between formulations is discussed. All formulations were well tolerated as evidenced by the absence of any reaction to injection either in the form of behavioural responses, injection site swelling or postmortem lesions. Sesame oil with ethyl oleate was the best parenteral vehicle tested for doramectin, allowing the expression of a high level of therapeutic and persistent efficacy and offering the benefit of excellent injection site toleration.

A method is described for the determination of abanoquil in human blood. The method is based on high-performance liquid chromatography (HPLC)/atmospheric pressure positive ion chemical ionization mass spectrometry, using (2H3)abanoquil as internal standard. Multiple reaction monitoring is employed for selectivity and sensitivity, which enables quantification over the range 10-500 pg ml-1 with acceptable precision and accuracy. This assay methodology illustrates the versatility of atmospheric pressure ionization/tandem mass spectrometry, in conjunction with HPLC, for the separation and quantification of drugs in the subnanogram per millilitre range.

The case is reported of a patient with central nervous system systemic lupus erythematosus (SLE) with features of progressive multifocal leucoencephalopathy (PML) seen clinically and by magnetic resonance imaging. A brain biopsy sample showed microinfarcts. The use of magnetic resonance imaging and IgG synthesis rates in evaluating central nervous system lupus, the co-occurrence of SLE and PML, and the differentiation of these entities by magnetic resonance imaging and by histology are considered.

Babesia divergens antigen obtained from bovine and gerbil erythrocytes was compared for the diagnosis of bovine babesiosis by the indirect immunofluorescence antibody test (IFAT) and the enzyme-linked immunosorbent assay (ELISA). Using a range of sera from the field and from experimental cattle, it was found that antigen from the two sources did not differ significantly in sensitivity or specificity. Antigen from gerbils may, therefore, be used for serological surveys of bovine babesiosis caused by B. divergens. The IFAT and ELISA were also compared and it was concluded that they are equally effective in the detection of positive samples. For small-scale surveys, the IFAT using gerbil-derived antigen is adequate, but for large surveys the ELISA is preferable.