Acute lower limb ischemia caused by vaccine-induced immune thrombotic thrombocytopenia: focus on perioperative considerations for 2 cases.

BACKGROUND: ChAdOx1 nCoV-19 (AstraZeneca) and Ad26COV2.S (Johnson & Johnson/Janssen) adenoviral vector vaccines have been associated with vaccine-induced immune thrombotic thrombocytopenia (VITT). Arterial thrombosis and acute limb ischemia have been described in a minority of patients with VITT. These patients usually need a revascularization, but they potentially are at a higher risk of complications. Optimal perioperative care of patients undergoing vascular surgery in acute VITT is unknown and important considerations in such context need to be described. CASES PRESENTATIONS: We report 2 cases of VITT presenting with acute limb ischemia who needed vascular surgery and we describe the multidisciplinary team decisions for specific treatment surrounding the interventions. Both patients' platelet counts initially increased after either intravenous immune globulin (IVIG) or therapeutic plasma exchange (TPE). None received platelet transfusion. They both received argatroban as an alternative to heparin for their surgery. Despite persistent positivity of anti-platelet factor 4 (PF4) antibodies and serotonin-release assay with added PF4 (PF4-SRA) in both patients, only one received a repeated dose of IVIG before the intervention. Per- and post-operative courses were both unremarkable. CONCLUSION: In spite of persistent anti-PF4 and PF4-SRA positivity in the setting of VITT, after platelet count improvement using either IVIG or TPE, vascular interventions using argatroban can show favorable courses. Use of repeated IVIG or TPE before such interventions still needs to be defined.

Right ventricle assessment in patients with pulmonary embolism at low risk for death based on clinical models: an individual patient data meta-analysis.

AIMS: Patients with acute pulmonary embolism (PE) at low risk for short-term death are candidates for home treatment or short-hospital stay. We aimed at determining whether the assessment of right ventricle dysfunction (RVD) or elevated troponin improves identification of low-risk patients over clinical models alone. METHODS AND RESULTS: Individual patient data meta-analysis of studies assessing the relationship between RVD or elevated troponin and short-term mortality in patients with acute PE at low risk for death based on clinical models (Pulmonary Embolism Severity Index, simplified Pulmonary Embolism Severity Index or Hestia). The primary study outcome was short-term death defined as death occurring in hospital or within 30 days. Individual data of 5010 low-risk patients from 18 studies were pooled. Short-term mortality was 0.7% [95% confidence interval (CI) 0.4-1.3]. RVD at echocardiography, computed tomography or B-type natriuretic peptide (BNP)/N-terminal pro BNP (NT-proBNP) was associated with increased risk for short-term death (1.5 vs. 0.3%; OR 4.81, 95% CI 1.98-11.68), death within 3 months (1.6 vs. 0.4%; OR 4.03, 95% CI 2.01-8.08), and PE-related death (1.1 vs. 0.04%; OR 22.9, 95% CI 2.89-181). Elevated troponin was associated with short-term death (OR 2.78, 95% CI 1.06-7.26) and death within 3 months (OR 3.68, 95% CI 1.75-7.74). CONCLUSION: RVD assessed by echocardiography, computed tomography, or elevated BNP/NT-proBNP levels and increased troponin are associated with short-term death in patients with acute PE at low risk based on clinical models. RVD assessment, mainly by BNP/NT-proBNP or echocardiography, should be considered to improve identification of low-risk patients that may be candidates for outpatient management or short hospital stay.

An interesting case of pyoderma gangrenosum with immature hystiocytoid neutrophils.

We present a unique case of a 36-year-old male who developed more than 20 pyoderma gangrenosum (PG) ulcers showing on histopathology a dense inflammatory infiltrate composed of histiocytoid mononuclear immature cells with a strong positivity for myeloperoxidase and Leder stain, suggesting a myeloid lineage in the absence of a concomitant myeloproliferative disorder. Histiocytoid Sweet syndrome (SS) is now recognized as a histological subtype of SS. Although PG and SS belong to the spectrum of neutrophilic diseases, to the best of our knowledge, this is the first case of a "Histiocytoid pyoderma gangrenosum" encompassing immature granulocytes in the absence of leukemia cutis.

Exaggerated Arthropod Bite Reaction During Pregnancy: A Case Report.

INTRODUCTION: The diagnosis of exaggerated bite reactions is based on the clinical and pathological characteristics of the lesions. These reactions can be an indicator of impending immune suppression. METHODS: The authors report the case of a 35-year-old pregnant woman who presented with a pruriginous vesicular and pustular eruption over her thighs and buttocks. The clinical and pathological findings were compatible with an exaggerated bite reaction. The patient did not report any severe or exaggerated reaction to insect bites in the past. It was her first episode. CONCLUSION: Exaggerated bite reactions have been described with hematological malignancies, mostly chronic lymphocytic leukemia. In our literature review, we did not find any reports of severe local bite reactions occurring during pregnancy. We hypothesize that the changes in the immune system during pregnancy might explain the development of exaggerated bite reactions in our patient.

Prognostic value of right ventricular dilatation in patients with low-risk pulmonary embolism.

The prognosis of multidetector computed tomography (MDCT) assessed right ventricular dilatation (RVD) is unclear in patients with pulmonary embolism (PE) and a simplified Pulmonary Embolism Severity Index (sPESI) of 0. We investigated in these patients whether MDCT-assessed RVD, defined by a right to left ventricular ratio (RV/LV) ≥0.9 or ≥1.0, is associated with worse outcomes.We combined data from three prospective cohorts of patients with PE. The main study outcome was the composite of 30-day all-cause mortality, haemodynamic collapse or recurrent PE in patients with sPESI of 0.Among 779 patients with a sPESI 0, 420 (54%) and 299 (38%) had a RV/LV ≥0.9 and ≥1.0 respectively. No difference in primary outcome was observed, 0.95% (95% CI 0.31-2.59) versus 0.56% (95% CI 0.10-2.22; p=0.692) and 1.34% (95% CI 0.43-3.62) versus 0.42% (95% CI 0.07-1.67; p=0.211) with RV/LV ≥0.9 and ≥1.0 respectively. Increasing the RV/LV threshold to ≥1.1, the outcome occurred more often in patients with RVD (2.12%, 95% CI 0.68-5.68 versus 0.34%, 95% CI 0.06-1.36; p=0.033).MDCT RV/LV ratio of ≥0.9 and ≥1.0 in sPESI 0 patients is frequent but not associated with a worse prognosis but higher cut-off values might be associated with worse outcome in these patients.

Flagellate Pattern of Toxic Erythema of Chemotherapy Due to Doxorubicin: A Case Report.

BACKGROUND: Doxorubicin is an antineoplastic agent frequently used in diverse cancer regimens. Cutaneous adverse effects have frequently been reported with its use. However, a flagellate-like dermatitis is not mentioned in the literature. OBJECTIVE: The investigators report a case of toxic erythema of chemotherapy with a flagellate pattern induced by doxorubicin. METHODS AND RESULTS: A 75-year-old woman with endometrial cancer received doxorubicin as part of her treatment. After her third cycle, she presented a pruritic vesiculobullous eruption, with linear elements that left hyperpigmented streaks on follow-up. A biopsy was compatible with a drug eruption. CONCLUSION: Doxorubicin is a well-known cause of toxic erythema of chemotherapy. As seen in this patient, the investigators suggest that it also be added to the list of causes of flagellate dermatosis.

Soil response to a 3-year increase in temperature and nitrogen deposition measured in a mature boreal forest using ion-exchange membranes.

The projected increase in atmospheric N deposition and air/soil temperature will likely affect soil nutrient dynamics in boreal ecosystems. The potential effects of these changes on soil ion fluxes were studied in a mature balsam fir stand (Abies balsamea [L.] Mill) in Quebec, Canada that was subjected to 3 years of experimentally increased soil temperature (+4 °C) and increased inorganic N concentration in artificial precipitation (three times the current N concentrations using NH4NO3). Soil element fluxes (NO3, NH4, PO4, K, Ca, Mg, SO4, Al, and Fe) in the organic and upper mineral horizons were monitored using buried ion-exchange membranes (PRS™ probes). While N additions did not affect soil element fluxes, 3 years of soil warming increased the cumulative fluxes of K, Mg, and SO4 in the forest floor by 43, 44, and 79 %, respectively, and Mg, SO4, and Al in the mineral horizon by 29, 66, and 23 %, respectively. We attribute these changes to increased rates of soil organic matter decomposition. Significant interactions of the heating treatment with time were observed for most elements although no clear seasonal patterns emerged. The increase in soil K and Mg in heated plots resulted in a significant but small K increase in balsam fir foliage while no change was observed for Mg. A 6-15 % decrease in foliar Ca content with soil warming could be related to the increase in soil-available Al in heated plots, as Al can interfere with the root uptake of Ca.

Rare scrotal chylous effusion: A case report.

Klippel-Trenaunay syndrome is a rare congenital malformation predominantly affecting lower limb. In most cases, it is characterized by a classic triad of cutaneous capillary malformation (port-wine stain), lymphatic and venous abnormalities, in association with variable soft tissue and bone overgrowths. We describe a 48-year-old male presenting on the genitalia several whitish vesicles discharging a milky fluid compatible with chyle. Extensive radiology workup revealed pelvic megalymphatic malformations. Pelvic lymphatic ligations and bleomycin sclerotherapy only allowed a partial improvement. Given the high potential of recurrence, the patient will soon undergo a genetic evaluation for PIK3CA gene mutation and may need further systemic treatment with Sirolimus. As this scrotal chylous effusion in the setting of Klippel-Trenaunay syndrome is rare and highly affects the quality of life, we wanted to raise awareness of this entity and its management.

Tree identity and diversity directly affect soil moisture and temperature but not soil carbon ten years after planting.

Soil C is the largest C pool in forest ecosystems that contributes to C sequestration and mitigates climate change. Tree diversity enhances forest productivity, so diversifying the tree species composition, notably in managed forests, could increase the quantity of organic matter being transferred to soils and alter other soil properties relevant to the C cycle.A ten-year-old tree diversity experiment was used to study the effects of tree identity and diversity (functional and taxonomic) on soils. Surface (0-10 cm) mineral soil was repeatedly measured for soil C concentration, C:N ratio, pH, moisture, and temperature in twenty-four tree species mixtures and twelve corresponding monocultures (replicated in four blocks).Soil pH, moisture, and temperature responded to tree diversity and identity. Greater productivity in above- and below-ground tree components did not increase soil C concentration. Soil pH increased and soil moisture decreased with functional diversity, more specifically, when species had different growth strategies and shade tolerances. Functional identity affected soil moisture and temperature, such that tree communities with more slow-growing and shade-tolerant species had greater soil moisture and temperature. Higher temperature was measured in communities with broadleaf-deciduous species compared to communities with coniferous-evergreen species.We conclude that long-term soil C cycling in forest plantations will likely respond to changes in soil pH, moisture, and temperature that is mediated by tree species composition, since tree species affect these soil properties through their litter quality, water uptake, and physical control of soil microclimates.

A case of durvalumab-induced lichenoid eruption evolving to bullous eruption after phototherapy: A case report.

Immune checkpoint inhibitor therapy nowadays became a treatment for a wide range of cancers, and may be responsible for various dermatologic adverse effects, including bullous eruptions. In our report, we present a case of late-onset immunotherapy-induced eruption in a 62-year-old woman treated with anti-programmed cell death-L1 agent durvalumab for metastatic squamous cell carcinoma. Diagnosed as lichenoid dermatitis upon initial presentation, this eruption evolved into necrotic bullous dermatitis after several weeks of phototherapy, with histology and direct immunofluorescence study favoring lichen planus pemphigoides. Thus, this case may be regarded as durvalumab-induced lichenoid dermatitis with phototherapy-triggered progression to necrotic lichen planus pemphigoides-like eruption. The patient's eruption responded to oral prednisone and immunotherapy interruption. Interestingly, durvalumab reintroduction in this patient led to recurrent lichenoid dermatitis without bullous component. This case of immunotherapy skin toxicity is rather distinctive by its clinical and histopathologic features, with phototherapy as an additional triggering factor.

A case of cutaneous necrosis due to intra-articular hyaluronic acid and treated with hyaluronidase.

A 66-year-old woman presented to the hospital with cutaneous necrosis of her right ankle and foot. Her symptoms began immediately after an intra-articular injection of hyaluronic acid for ankle osteoarthritis, which was performed 6 days before. Histopathology showed an intra-vascular hyaluronic acid embolus. The initial treatment approach was conservative, but the patient's clinical state degraded. She was thus treated with sub-cutaneous hyaluronidase, the enzyme that degrades hyaluronic acid, which yielded a moderate improvement even though it was administered 22 days after the initial hyaluronic acid injection. Although hyaluronic acid embolism and subsequent cutaneous necrosis are well-known complications of dermal fillers, there are few reported cases of embolism following intra-articular injection. To our knowledge, this is the first time hyaluronidase has been used in this setting.

129I and 247Cm in meteorites constrain the last astrophysical source of solar r-process elements.

The composition of the early Solar System can be inferred from meteorites. Many elements heavier than iron were formed by the rapid neutron capture process (r-process), but the astrophysical sources where this occurred remain poorly understood. We demonstrate that the near-identical half-lives [Formula: see text] of the radioactive r-process nuclei iodine-129 and curium-247 preserve their ratio, irrespective of the time between production and incorporation into the Solar System. We constrain the last r-process source by comparing the measured meteoritic ratio 129I/247Cm = 438 ± 184 with nucleosynthesis calculations based on neutron star merger and magneto-rotational supernova simulations. Moderately neutron-rich conditions, often found in merger disk ejecta simulations, are most consistent with the meteoritic value. Uncertain nuclear physics data limit our confidence in this conclusion.

Treatment of moderate to severe psoriasis with apremilast over 2 years in the context of long-term treated HIV infection: A case report.

Treatment of moderate-to-severe psoriasis in patients with HIV infection is a clinical challenge. We present the case of a patient with a longstanding history of well-controlled HIV. He had failed topical management, and his hypertriglyceridemia made use of acitretin potentially unsafe. He was unable to regularly attend a phototherapy unit. Physical examination revealed 12% total body surface area involvement with a Psoriasis Area Severity Index (PASI) of 10.2. His Dermatology Quality of Life Index (DLQI) was 20. After 3 months of apremilast treatment, his PASI decreased to 4.1. After 7 months, his PASI decreased to 2.7 and his DLQI to 1. Two years later, his PASI score was 2.4, with a stable CD4 count of 1200 cells/mm3 and an undetectable viral load. There were no serious opportunistic infections or laboratory abnormalities. To our knowledge, this represents the second reported case of psoriasis treatment with apremilast in a patient with HIV.

A Monte Carlo study on the effect of seed design on the interseed attenuation in permanent prostate implants.

Standard algorithms for postimplant analysis of transperineal interstitial permanent prostate brachytherapy (TIPPB) are based on AAPM Task Group 43 formalism (TG-43), which makes use of a world entirely made of water. This entails an assignment of the prostate, surrounding organs at risk, as well as all brachytherapy seeds present in a permanent prostate implant to water. Brachytherapy seeds are generally made from high atomic number materials. Because of the simultaneous presence of many brachytherapy seeds in a TIPPB, there is a shielding effect causing an attenuation of energy of the emitted photons generally called the "interseed attenuation" (ISA). This study investigates the impact of seed designs and compositions on the interseed attenuation. For this purpose, six brachytherapy seeds covering a wide variety of seed design and composition were modeled with the GEANT4 Monte Carlo (MC) toolkit. MC has allowed calculation of the contribution of each major component (encapsulation and internal components) of a given seed model to ISA separately. The impact of ISA on real clinical implant configurations was also explored. Two clinical postimplant geometries with different brachytherapy seeds were studied with MC simulations. The change in the clinical parameter D90 was observed. This study shows that Nucletron SelectSeed (similar to the Oncura model 6711), ProstaSeed, and Best Medical model 2335 are the most attenuating designs with 4.8%, 3.9%, and 4.6% of D90 reduction, respectively. The least attenuating seed is a 103Pd seed encapsulated in a polymer shell, the IBt OptiSeed with 1.5%. Finally, based on this systematic study, a new seed design is proposed that is predicted to be the most waterlike brachytherapy seed and thus TG-43 compatible.

Extractability of elements in sugar maple xylem along a gradient of soil acidity.

Dendrochemistry has been used for the historical dating of pollution. Its reliability is questionable due primarily to the radial mobility of elements in sapwood. In the present study, the extractability of seven elements was characterized to assess their suitability for the monitoring of environmental conditions. Nine mature sugar maple trees (Acer saccharum Marsh.), a wide-ranging species in eastern North America that has suffered decline in past decades, were sampled in three Quebec watersheds along a soil acidity gradient. Five-year groups of annual tree rings were treated by sequential chemical extractions using extractants of varying strength (deionized H2O, 0.05 M HCl, and concentrated HNO(3)) to selectively solubilize the elements into three fractions (water-soluble, acid-soluble, and residual). Monovalent K; divalent Ba, Ca, Cd, Mg, Mn; and trivalent Al cations were found mostly in the water-soluble, acid-soluble, and residual fractions, respectively. Forms more likely to be mobile within the tree (water-soluble and acid-soluble) do not seem to be suitable for temporal monitoring because of potential lateral redistribution in sapwood rings. However, certain elements (Cd, Mn) were responsive to current soil acidity and could be used in spatial variation monitoring. Extractability of Al varied according to soil acidity; at less acidic sites, up to 90% of Al was contained in the residual form, whereas on very acidic soils, as much as 45% was found in the water-soluble and acid-soluble fractions. Sequential extractions can be useful for determining specific forms of metals as key indicators of soil acidification.

Insulin secretion kinetics from single islets reveals distinct subpopulations.

Type II diabetes progresses with inadequate insulin secretion and prolonged elevated circulating glucose levels. Also, pancreatic islets isolated for transplantation or tissue engineering can be exposed to glucose over extended timeframe. We hypothesized that isolated pancreatic islets can secrete insulin over a prolonged period of time when incubated in glucose solution and that not all islets release insulin in unison. Insulin secretion kinetics was examined and modeled from single mouse islets in response to chronic glucose exposure (2.8-20 mM). Results with single islets were compared to those from pools of islets. Kinetic analysis of 58 single islets over 72 h in response to elevated glucose revealed distinct insulin secretion profiles: slow-, fast-, and constant-rate secretors, with slow-secretors being most prominent (ca., 50%). Variations in the temporal response to glucose therefore exist. During short-term (<4 h) exposure to elevated glucose few islets are responding with sustained insulin release. The model allowed studying the influence of islet size, revealing no clear effect. At high-glucose concentrations, when secretion is normalized to islet volume, the tendency is that smaller islets secrete more insulin. At high-glucose concentrations, insulin secretion from single islets is representative of islet populations, while under low-glucose conditions pooled islets did not behave as single ones. The characterization of insulin secretion over prolonged periods complements studies on insulin secretion performed over short timeframe. Further investigation of these differences in secretion profiles may resolve open-ended questions on pre-diabetic conditions and transplanted islets performance. This study deliberates the importance of size of islets in insulin secretion. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:1059-1068, 2018.

Determinants and prognostic implication of diagnostic delay in patients with a first episode of pulmonary embolism.

Signs and symptoms of pulmonary embolism (PE) are not specific and this can lead to a diagnostic delay. Little is known about the determinants of this delay and its prognostic implication. We conducted a retrospective analysis of a prospective cohort involving 514 patients with a first episode of PE. The diagnostic delay was defined as a time from first symptom onset to diagnosis of >3 days, corresponding of the median time in the population. Multivariable logistic regression analysis was performed to identify determinants of diagnostic delay. Prognostic implication was measured as the occurrence of 30-day all-cause mortality, haemodynamic collapse or recurrent PE. A total of 240 (47%) among 514 patients had a time from first symptom to diagnosis > 3 days. Previous deep vein thrombosis (OR 0.55, 95% Confidence Interval (CI), 0.32-0.93), immobilization (OR 0.52, 95% CI, 0.28-0.96), surgery (OR 0.31, 95% CI, 0.16-0.62), chest pain (OR 0.58, 95% CI, 0.39-0.86), syncope (OR 0.48, 95% CI, 0.23-1.01), dyspnea (OR 2.48, 95% CI, 1.57-3.91) and hemoptysis (OR 3.57, 95% CI, 1.40-9.07) were associated with diagnostic delay. Twenty-two patients (4.3%, 95%CI, 2.8-6.5) experienced an outcome event within 30 days. Among them, 15 patients (6.2% 95%CI, 3.7-10.3) had a diagnostic delay and 7 (2.6%, 95% CI 1.1-5.4) did not (p = 0.039). In this cohort, diagnostic delay is associated with the absence of major risk factors for PE or clinical features such as chest pain or syncope and the presence of dyspnea or hemoptysis. Diagnostic delay is associated with a worse 30-day prognosis.

A role for auto-immunity in chronic rhinosinusitis? Lessons learned from sub-epidermal bullous disorders of the skin.

Chronic rhinosinusitis (CRS) is a frequent chronic condition, which has origins in complex interactions between genetic, immunological and microbial factors. The role of auto-immunity in CRS remains unclear, although recent studies have started to emerge in CRS patient refractory to maximal medical management. We discuss the possible auto-immunity link between CRS and other skin diseases, in particular acquired bullous dermatoses, and review the current evidence. We raise additional considerations for auto-immunity from both research and clinical standpoints.