Search

Chemotherapy‐induced radiation recall reactions are rare, commonly affecting skin but can affect internal organs. Treatments include antihistamines and topical steroids and discontinuation of therapy if severe. Rechallenge may not cause recurrence.

An 80 year old man with metastatic castrate-resistant prostate cancer was treated with multiple systemic agents but after carboplatin/paclitaxel, developed a morbilliform rash conforming precisely to a skin site of previous palliative radiotherapy, a so-called radiation recall reaction.

We demonstrate a low-cost diffuser-based computational funduscope that can recover pathological features of the model eye fundus. Our device achieves over 33° FOV and is robust to 4D refractive error using a single-shot point-spread-function.

Oblique back-illumination capillaroscopy has recently been introduced as an efficient method for non-invasive blood cell imaging in human capillaries. To apply this technique to clinical blood cell counting, solutions for automatic processing of acquired videos are needed. Here, we take the first step towards this goal, by introducing a novel deep learning multi-cell tracking model, named CycleTrack, which achieves accurate blood cell counting from capillaroscopic videos. CycleTrack combines two simple online tracking models, SORT and CenterTrack, and is tailored to features of capillary blood cell flow. Blood cells are tracked by displacement vectors in two opposing temporal directions between consecutive frames. This approach yields accurate tracking despite rapidly moving and deforming blood cells. The proposed model outperforms other baseline trackers, achieving \(66.3\%\) MOTA and \(75.1\%\) ID F1 score on test videos. CycleTrack achieves an average cell counting error of \(3.42\%\) among 8 1000-frame test videos, compared to \(6.55\%\) and \(22.98\%\) from original CenterTrack and SORT, with negligible time expense. It takes 800s to track and count approximately 8000 blood cells from 9,600 frames captured in a typical one-minute video. Moreover, the blood cell velocity measured by CycleTrack demonstrates a consistent, pulsatile pattern within the physiological range of heart rate. The project code is accessible online at: https://github.com/DurrLab/CycleTrack.

PURPOSE: To evaluate vision and corneal surface regularity after each step of a three-step surgical treatment of keratoconus and post–laser in situ keratomileusis (LASIK) ectasia (implantation of intracorneal ring segments [ICRS], corneal cross-linking [CXL], and implantation of toric intraocular contact lenses [ICLs]). METHODS: Thirty-one eyes of 24 patients with moderate to severe keratoconus and post-LASIK ectasia (stages II and III of Amsler–Krumeich classification) were included. All eyes underwent all three steps. The time interval between ICRS implantation and CXL was 4 to 6 weeks, and ICL implantation was performed 6 to 8 months after CXL. Visual acuity, refraction, and corneal topometric indices were evaluated with the Pentacam system (index of surface variance [ISV], index of vertical asymmetry [IVA], keratoconus index [KI], central keratoconus index [CKI], index of height asymmetry [IHA], index of height decentration [IHD], and corneal wavefront parameters [eg, higher order aberrations, spherical aberration, and coma]). RESULTS: Decimal uncorrected distance visual acuity (UDVA) improved from 0.13 ± 0.17 preoperatively to 0.69 ± 0.18 at 1 year, whereas corrected distance visual acuity (CDVA) improved from 0.56 ± 0.24 to 0.80 ± 0.18, respectively. The topometric indices ISV, IVA, KI, and IHD also improved significantly, whereas CKI and IHA showed no significant improvement. Higher order aberrations, spherical aberration, and coma improved significantly compared to baseline. CONCLUSIONS: The combined use of ICRS, CXL, and ICL implantation significantly improves visual acuity, higher order aberrations, and corneal shape in moderate and severe keratoconus and post-LASIK ectasia. [ J Refract Surg . 2020;36(2):104–109.]

Oblique plane microscopy (OPM) enables high speed, volumetric fluorescence imaging through a single-objective geometry. While these advantages have positioned OPM as a valuable tool to probe biological questions in animal models, its potential for in vivo human imaging is largely unexplored due to its typical use with exogenous fluorescent dyes. Here we introduce a scattering-contrast oblique plane microscope (sOPM) and demonstrate label-free imaging of blood cells flowing through human capillaries in vivo. The sOPM illuminates a capillary bed in the ventral tongue with an oblique light sheet, and images side- and back- scattered signal from blood cells. By synchronizing sOPM with a conventional capillaroscope, we acquire paired widefield and axial images of blood cells flowing through a capillary loop. The widefield capillaroscope image provides absorption contrast and confirms the presence of red blood cells (RBCs), while the sOPM image may aid in determining whether optical absorption gaps (OAGs) between RBCs have cellular or acellular composition. Further, we demonstrate consequential differences between fluorescence and scattering versions of OPM by imaging the same polystyrene beads sequentially with each technique. Lastly, we substantiate in vivo observations by imaging isolated red blood cells, white blood cells, and platelets in vitro using 3D agar phantoms. These results demonstrate a promising new avenue towards in vivo blood analysis., 12 pages, 6 figures

Febrile neutropenia (FN) is a common cause of hospitalization for cancer patients undergoing chemotherapy treatment. To screen for FN, patients require invasive blood draws and complete blood cell counts, which increases risk of nosocomial infection while in an immunocompromised state. There is a pressing clinical need for non-invasive, point-of-care technology to frequently screen for FN, which, if detected early, can be prophylactically managed. A promising approach to address this need is capillaroscopy, through which blood cells are imaged in capillaries non-invasively. Visualization of shadows caused by absorption of individual red blood cells is currently achievable, and correlation between the absence of optical absorption gaps and severe neutropenia has been observed. However, a completely accurate identification of the physical origin of these optical absorption gaps for conclusive neutropenia diagnosis remains an elusive task. Here we present scattering oblique plane microscopy as a means of imaging moving scattering particles within a turbid medium with the goal of eventually imaging and characterizing blood cells in vivo flowing in superficial capillaries. Our imaging system illuminates an oblique light sheet through a capillary bed and collects back-scatter using a single objective at frame rates of >200 Hz. To validate this system, we develop phantoms mimicking capillaries with 200 μm diameter lumens embedded deep in silicone doped with TiO2 and India ink. Single 3 μm diameter polystyrene beads flowing through the capillaries are resolved with a signal to noise ratio of approximately 5:1 at a depth of 1 mean free path.

We present a non-invasive, label-free method of imaging blood cells flowing through human capillaries in vivo using oblique back-illumination capillaroscopy (OBC). Green light illumination allows simultaneous phase and absorption contrast, enhancing the ability to distinguish red and white blood cells. Single-sided illumination through the objective lens enables 200 Hz imaging with close illumination-detection separation and a simplified setup. Phase contrast is optimized when the illumination axis is offset from the detection axis by approximately 225 um when imaging 80 um deep in phantoms and human ventral tongue. We demonstrate high-speed imaging of individual red blood cells, white blood cells with sub-cellular detail, and platelets flowing through capillaries and vessels in human tongue. A custom pneumatic cap placed over the objective lens stabilizes the field of view, enabling longitudinal imaging of a single capillary for up to seven minutes. We present high-quality images of blood cells in individuals with Fitzpatrick skin phototypes II, IV, and VI, showing that the technique is robust to high peripheral melanin concentration. The signal quality, speed, simplicity, and robustness of this approach underscores its potential for non-invasive blood cell counting., Comment: 10 pages, 7 Figures

Graphical abstract, The assessment of Parkinson’s disease currently relies on the history of the present illness, the clinical interview, the physical examination, and structured instruments. Drawbacks to the use of clinical ratings include the reliance on real-time human vision to quantify small differences in motion and significant inter-rater variability due to inherent subjectivity in scoring the procedures. Rating tools are semi-quantitative by design, however, in addition to significant inter-rater variability, there is inherent subjectivity in administering these tools, which are not blinded in clinical settings. Sophisticated systems to quantify movements are too costly to be used by some providers with limited resources. A simple procedure is described to obtain continuous quantitative measurements of movements of people with Parkinson’s disease for objective analysis and correlation with visual observation of the movements. • Inexpensive accelerometers are attached to the upper and lower extremities of patients with Parkinson’s disease and related conditions to generate a continuous, three-dimensional recorded representation of movements occurring while performing tasks to characterize the deficits of Parkinson’s disease. • Movements of the procedure are rated by trained examiners live in real-time and later by videotapes. • The output of the instrumentation can be conveyed to experts for interpretation for diagnostic and therapeutic purposes.

Clinical radiosensitivity is a significant impediment to tumour control and cure, in that it restricts the total doses which can safely be delivered to the whole radiotherapy population, within the tissue tolerance of potentially radiosensitive (RS) individuals. Understanding its causes could lead to personalization of radiotherapy.We screened tissues from a unique bank of RS cancer patients for expression defects in major DNA double-strand break repair proteins, using Western blot analysis and subsequently reverse-transcriptase polymerase chain reaction and pulsed-field gel electrophoresis.We hypothesized that abnormalities in expression of these proteins may explain the radiosensitivity of some of our cancer patients. The cells from one patient showed a reproducibly consistent expression reduction in two complex-forming DNA double-strand break repair protein components (DNA Ligase IV and XRCC4). We also showed a corresponding reduction in both gene products at the mRNA level. Additionally, the mRNA inducibility by ionizing radiation was increased for one of the proteins in the patient's cells. We confirmed the likely functional significance of the non-homologous end-joining (NHEJ) expression abnormalities with a DNA double strand break (DNA DSB) repair assay.We have identified a novel biological phenotype linked to clinical radiosensitivity. This is important in that very few molecular defects are known in human radiotherapy subjects. Such knowledge may contribute to the understanding of radiation response mechanisms in cancer patients and to personalization of radiotherapy.

An 83-year-old female was treated with mastectomy and postoperative radiotherapy for breast cancer 30 years prior to developing a new small patch of thickening and scaliness on her left upper back, within the previous radiotherapy field. Serial excision biopsies revealed this to be a lymphangioendothelioma with no suggestion of malignancy. In early 2006 the lesion began to enlarge and take on a more erythematous plaque-like appearance. She was reviewed by a specialist dermatologist and an excision biopsy revealed a low-grade cutaneous angiosarcoma; this was approximately 38 years after radiotherapy to this region, the longest reported period between irradiation and in-field angiosarcoma development (the previous being 16 years). To our knowledge, this is the first case of post-radiotherapy angiosarcoma with a diagnosed precursor lesion. The lesion was treated with surgical excision and adjuvant radiotherapy. After further in- and out of- field recurrences, low dose radiotherapy elicited a surprisingly rapid and complete response within the treated areas; this was unusual in that these tumours are characteristically radiation-resistant. The radiosensitive case we report here raises the possibility that radiation should be more widely considered in the therapy of this disease. Methods of treatment of this rare malignancy are discussed.

Background: Understanding the basis of clinical radiosensitivity is a key goal of radiation research. In this study, we used the limiting dilution assay (LDA) to analyze in vitro radiosensitivity of cell lines from individuals with breast and other cancers, who had been treated with ionizing radiation, and who either had a non-radiosensitive (RS) radiation response or who were clinically RS. Methods: Lymphoblastoid cell lines (LCLs) were created from 29 cancer patients including 19 RS patients, 10 controls who had not developed severe normal tissue reactions, and 1 ataxia telangiectasia RS control cell line. The clinically RS patients had grade 3 or grade 4 reactions; one had a grade 2 reaction. All cells were exposed to graded doses of gamma-radiation in vitro and cell survival assessed via LDA. Cell survival was expressed on non-linear regression analysis-fitted survival curves and also as the surviving fraction at 2 Gray (Gy) (SF2). Results: Our LDA analysis yielded two notable positive results. Firstly, it could distinguish control cells from cells from pooled breast cancer cases with severe reactions of all types (acute reactors, consequential late reactors and late reactors). Secondly, two radiosensitivity outliers were detected on the fitted curves, corresponding clinically to grade 3 and 4 late radiation reactions in breast and head and neck cancer cases respectively. The assay showed considerable cell survival heterogeneity. Conclusions: The LDA as used here may provide unique clinical utility in detecting potential RS breast cancer patients prior to radiotherapy (RT), a form of personalized medicine. The assay may be especially useful in situations where its results can be temporally available prior to therapy initiation (e.g., those patients not undergoing RT until some months after surgery, typically those having adjuvant chemotherapy prior to RT). Two LCLs from RS outliers could potentially yield insight into the cellular and/or genetic basis of radiosensitivity, for example by undertaking genomic analyses on these cell lines.

In this chapter we focus on the detailed, operational modeling of Emergency Departments—the flows and general processes, and not on clinical decision making. On the flow level, an Emergency Department shares a number of characteristics with a general repair shop, and while there are key differences, the flow and resource interrelationships are similar. We use this perspective to assist researchers with the decomposition and analysis of Emergency Departments, as well as the review of detailed research on Emergency Departments. We examine the scope of research efforts, methodologies employed, types of data included in the modeling, and the implementation of research results in practice. The chapter is anchored by an extensive field study at a medium-sized Emergency Department, whose methodology and key results are presented along with insights from the hospital.

The case is presented of a 66 year old woman who attended the emergency department with severe abdominal pain subsequent to a bout of coughing, following a week's history of productive cough. She was known to have chronic obstructive pulmonary disease and was also on warfarin for recurrent deep vein thromboses. She had no history of ichaemic heart disease. She was found to have a rectus sheath haematoma and an international normalised ratio of 7.7, and admission was arranged for coagulation control and analgesia. However, a routine electrocardiograph (ECG) demonstrated an ST elevation pattern consistent with an acute inferior infarction. Subsequent ECGs showed no ST elevation, although the axis and chest lead QRS morphology remained the same throughout the first 12 hours. Over the next three days, R wave progression decreased in the chest leads. Troponin I at admission and 24 hours later were both

Rabies is endemic worldwide, and causes approximately 30 000 deaths per year. In the past 20 years, 12 deaths have occurred in the UK, although all but one case were contracted overseas. We have reviewed the current literature regarding the management of possible rabies exposure in the setting of a UK emergency department. The article offers an overview of rabies, including pathology, risk assessment, and current treatment, including both pre-exposure and post-exposure prophylaxis. We have also included a form online, which allows the correct information to be obtained and recorded prior to seeking advice from the local virology services.

Successful defibrillation of a patient with dextrocardia using conventional anterolateral paddle positions raises doubts about the necessity to place paddles in the exact recommended positions. Evidence found relates either to volunteers in a laboratory setting or to defibrillation of atrial arrhythmias. The conclusion is that there is no published difference either in transthoracic impedance or in success of defibrillation between anteroposterior and anterolateral paddle positions. In the absence of any evidence for an ideal apical paddle position in the standard anterolateral defibrillation of ventricular arrhythmias, the emphasis in ALS and resuscitation guidelines on “correct” positioning seems misplaced, and, by adding unnecessary information, may hinder learning the skill of defibrillation. Early defibrillation is crucial to successful recovery from cardiac arrest and anything that delays cardioversion should be avoided. The limited evidence suggests that the exact position of the paddles does not matter. The time taken to find the “correct” position is time wasted and it may instead be preferable to teach people merely to place the apical paddle to the left of the nipple in the midaxillary line.

Background: Docetaxel is used as first line chemotherapy for metastatic castrate resistant prostate cancer (mCRPC). It has been reported that castrated men have substantially increased docetaxel clearance (CL) compared to uncastrated men treated for mCRPC (Franke et al, J Clin Oncol 28: 4562−7, 2010). These results were obtained from 20 castrated men, with 10 non-castrated men serving as controls. In this study, we aimed to validate these findings in a larger and independent cohort of patients. Material and Methods: All male patients treated within the context of a pharmacokinetic study (Dutch Trial Registry; NTR2311) with docetaxel for solid tumors were included in this analysis (n = 74). As chemotherapy alone does not result in alterations in testosterone levels, out of these 74 patients, all men with non-prostate tumors served as controls (n = 36) of the castrated mCRPC patients (n = 38). Five of these control patients received docetaxel in combination with SU014813 in a clinical phase I study, all other patients received monotherapy. SU014813 has no clinically relevant pharmacokinetic (PK) interaction with docetaxel (de Jonge et al, Eur J Cancer 47: 1328−35, 2011). Dosage ranged from 30mg/m to 100mg/m, given in different schedules. Plasma docetaxel levels were determined by HPLC or LC-MS/MS. Individual PK parameters were estimated from previously developed population PK models by non-linear mixed effects modelling using NONMEM software. P-values were calculated using an independent samples T-test, while linear regression analysis was used to adjust for age, ethnicity, body surface area, concomitant use of other anticancer drugs, and dose when analysing haematological toxicity. Results: In the castrated patients, there was an increased docetaxel CL compared to the CL of uncastrated men (48.4 L/h versus 42.1 L/h, P = 0.051). In addition, both absolute neutrophil count nadir (n = 66) and white blood cell count nadir (n = 68) were significantly higher in castrated patients during chemotherapy with docetaxel (4.1 versus 1.7 ×109/L, P = 0.003 and 5.3 versus 3.1×109/L, P = 0.016, respectively). Conclusions: Androgen deprived prostate cancer patients in this study show an increased CL. In addition, castrated patients show less pronounced haematological toxicity compared to the control group of uncastrated men treated with docetaxel. Adding these results to the existing knowledge provides a solid foundation for further investigations regarding the increase in clearance related to castration-status and also for the individualization of docetaxel treatment in male patients.

In three infants with neonatal lacticacidaemia, a deficiency in the E1 (pyruvate dehydrogenase) component of the pyruvate dehydrogenase complex was demonstrated in skin fibroblast cultures. Residual activities of the pyruvate dehydrogenase complex in the activated state were 1.6%, 3.9% and 18.8% of control values, respectively. Immunoprecipitation of extracts of cultures skin fibroblasts grown on 35S-methionine with anti-pyruvate dehydrogenase complex antibody revealed an abnormality in the E1 alpha-component of these three patients when visualised after sodium dodecyl sulphate/polyacrylamide gel electrophoresis. This component appeared to have a slightly lower molecular weight than did this protein from control cell strains. Cell strains from other patients with a deficiency of the pyruvate dehydrogenase complex did not exhibit this defect. Three patients also showed dysmorphism and developmental abnormalities of the central nervous system.