First-in-Class Humanized Antibody against Alternatively Spliced Tissue Factor Augments Anti-Metastatic Efficacy of Chemotherapy in a Preclinical Model of Pancreatic Ductal Adenocarcinoma.

Alternatively spliced tissue factor (asTF) promotes the progression of pancreatic ductal adenocarcinoma (PDAC) by activating ß1-integrins on PDAC cell surfaces. hRabMab1, a first-in-class humanized inhibitory anti-asTF antibody we recently developed, can suppress PDAC primary tumor growth as a single agent. Whether hRabMab1 has the potential to suppress metastases in PDAC is unknown. Following in vivo screening of three asTF-proficient human PDAC cell lines, we chose to make use of KRAS G12V-mutant human PDAC cell line PaCa-44, which yields aggressive primary orthotopic tumors with spontaneous spread to PDAC-relevant anatomical sites, along with concomitant severe leukocytosis. The experimental design featured orthotopic tumors formed by luciferase labeled PaCa-44 cells; administration of hRabMab1 alone or in combination with gemcitabine/paclitaxel (gem/PTX); and the assessment of the treatment outcomes on the primary tumor tissue as well as systemic spread. When administered alone, hRabMab1 exhibited poor penetration of tumor tissue; however, hRabMab1 was abundant in tumor tissue when co-administered with gem/PTX, which resulted in a significant decrease in tumor cell proliferation; leukocyte infiltration; and neovascularization. Gem/PTX alone reduced primary tumor volume, but not metastatic spread; only the combination of hRabMab1 and gem/PTX significantly reduced metastatic spread. RNA-seq analysis of primary tumors showed that the addition of hRabMab1 to gem/PTX enhanced the downregulation of tubulin binding and microtubule motor activity. In the liver, hRabMab1 reduced liver metastasis as a single agent. Only the combination of hRabMab1 and gem/PTX eliminated tumor cell-induced leukocytosis. We here demonstrate for the first time that hRabMab1 may help suppress metastasis in PDAC. hRabMab1's ability to improve the efficacy of chemotherapy is significant and warrants further investigation.

Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management.

DISEASE OVERVIEW: Polycythemia vera (PV) is a JAK2-mutated myeloproliferative neoplasm characterized by clonal erythrocytosis; other features include leukocytosis, thrombocytosis, splenomegaly, pruritus, constitutional symptoms, microcirculatory disturbances, and increased risk of thrombosis and progression into myelofibrosis (post-PV MF) or acute myeloid leukemia (AML). DIAGNOSIS: A working diagnosis is considered in the presence of a JAK2 mutation associated with hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women; morphologic confirmation by bone marrow examination is advised but not mandated. CYTOGENETICS: Abnormal karyotype is seen in 15%-20% of patients with the most frequent sole abnormalities being +9 (5%), loss of chromosome Y (4%), +8 (3%), and 20q- (3%). MUTATIONS: Over 50% of patients harbor DNA sequence variants/mutations other than JAK2, with the most frequent being TET2 (18%) and ASXL1 (15%). Prognostically adverse mutations include SRSF2, IDH2, RUNX1, and U2AF1, with a combined incidence of 5%-10%. SURVIVAL AND PROGNOSIS: Median survival is ⁓15 years but exceeds 35 years for patients aged ≤40 years. Risk factors for survival include older age, leukocytosis, abnormal karyotype, and the presence of adverse mutations. Twenty-year risk for thrombosis, post-PV MF, or AML are ⁓26%, 16% and 4%, respectively. RISK FACTORS FOR THROMBOSIS: Two risk categories are considered: high (age >60 years or thrombosis history) and low (absence of both risk factors). Additional predictors for arterial thrombosis include cardiovascular risk factors and for venous thrombosis higher absolute neutrophil count and JAK2V617F allele burden. TREATMENT: Current goal of therapy is to prevent thrombosis. Periodic phlebotomy, with a hematocrit target of <45%, combined with once- or twice-daily aspirin (81 mg) therapy, absent contraindications, is the backbone of treatment in all patients, regardless of risk category. Cytoreductive therapy is reserved for high-risk disease with first-line drugs of choice being hydroxyurea and pegylated interferon-α and second-line busulfan and ruxolitinib. In addition, systemic anticoagulation is advised in patients with venous thrombosis history. ADDITIONAL TREATMENT CONSIDERATIONS: At the present time, we do not consider a drug-induced reduction in JAK2V617F allele burden, which is often incomplete and seen not only with peg-IFN but also with ruxolitinib and busulfan, as an indicator of disease-modifying activity, unless accompanied by cytogenetic and independently-verified morphologic remission. Accordingly, we do not use the specific parameter to influence treatment choices. The current review also includes specific treatment strategies in the context of pregnancy, splanchnic vein thrombosis, pruritus, perioperative care, and post-PV MF.

Neuroleptic malignant syndrome associated with atypical antipsychotics: A case report.

INTRODUCTION: Neuroleptic malignant syndrome (NMS) is uncommon, with an incidence of 0.01%-3.23%, and is associated with the use of drugs that intervene with dopamine, causing hyperthermia, muscular rigidity, confusion, autonomic instability and death. CASE REPORT: A 35-year-old man with a history of catatonia, refractory epilepsy and functional impairment, required frequent changes in his anticonvulsant and antipsychotic treatment, due to adverse effects. During 2019, in the month of July, clozapine was changed to amisulpride, in September he developed fever, muscle stiffness, stupor, diaphoresis and tachypnea over a two-week period; paraclinical tests showed elevated creatine phosphokinase (CPK) and leukocytosis, so NMS was considered. The antipsychotic was withdrawn and he was treated with bromocriptine and biperiden, with a good response. Ten days after discharge, he began treatment with olanzapine, which generated a similar episode to the one described in December, with subsequent management and resolution. DISCUSSION: The diagnosis is based on the use of drugs that alter dopamine levels, plus altered state of consciousness, fever, autonomic instability and paraclinical tests showing leukocytosis and elevated CPK. Differential diagnoses must be ruled out. Early diagnosis generally leads to total remission, although some patients will suffer complications, long-term sequelae or recurrences. The recurrence in this case derived from the early reintroduction of the neuroleptic after the first episode. Treatment should be individualised according to severity to avoid mortality. CONCLUSIONS: Atypical antipsychotics are rarely suspected of generating NMS. Moreover, the time to reintroduction after an episode must also be taken into account.

Valproate-related neutropenia and lithium-related leukocytosis in patients treated with clozapine: a retrospective cohort study.

BACKGROUND: Neutropenia is a noteworthy side effect of clozapine, which might warrant this drugs' discontinuance for safety. Studies have revealed that the risk of neutropenia increases with concurrent administration of valproate, but the evidence was limited. Conversely, lithium may have an ameliorating effect on clozapine-induced neutropenia. This study explored the effects of valproate and lithium on white blood cell counts in patients treated with clozapine. METHODS: We retrospectively investigated the electronic medical records from one tertiary psychiatric hospital in Taiwan and enrolled patients discharged between January 1, 2006, and December 31, 2017, with clozapine prescriptions. We scrutinized their demographic data, medications, and hematological results at discharge and during follow-up outpatient clinic visits over the subsequent 3 years. Patients were classified into four groups: clozapine only (CLO), clozapine and valproate (CLO + VAL), clozapine and lithium (CLO + Li), and clozapine, valproate, and lithium (CLO + VAL + Li). We also identified hematological events (neutropenia or leukocytosis) of these patients during outpatient follow-ups. RESULTS: Of the included 1084 patients, 55(5.1%) developed neutropenia. Concurrent valproate use (odds ratio [OR] = 3.49) and older age (p = .007) were identified as risk factors. Moreover, 453 (41.79%) patients developed leukocytosis. Younger age; male sex; and concurrent use of lithium (OR = 3.39, p < .001), clozapine daily dosage, and benzodiazepines were the risk factors for leukocytosis. CONCLUSION: Concurrent valproate use and older age are associated with the development of neutropenia in patients treated with clozapine. Concurrent lithium usage, younger age, male sex, and concurrent benzodiazepine use might be related to leukocytosis.

Phage therapy in a lung transplant recipient with cystic fibrosis infected with multidrug-resistant Burkholderia multivorans.

BACKGROUND: There is increased interest in bacteriophage (phage) therapy to treat infections caused by antibiotic-resistant bacteria. A lung transplant recipient with cystic fibrosis and Burkholderia multivorans infection was treated with inhaled phage therapy for 7 days before she died. METHODS: Phages were given via nebulization through the mechanical ventilation circuit. Remnant respiratory specimens and serum were collected. We quantified phage and bacterial deoxyribonucleic acid (DNA) using quantitative polymerase chain reaction, and tested phage neutralization in the presence of patient serum. We performed whole genome sequencing and antibiotic and phage susceptibility testing on 15 B. multivorans isolates. Finally, we extracted lipopolysaccharide (LPS) from two isolates and visualized their LPS using gel electrophoresis. RESULTS: Phage therapy was temporally followed by a temporary improvement in leukocytosis and hemodynamics, followed by worsening leukocytosis on day 5, deterioration on day 7, and death on day 8. We detected phage DNA in respiratory samples after 6 days of nebulized phage therapy. Bacterial DNA in respiratory samples decreased over time, and no serum neutralization was detected. Isolates collected between 2001 and 2020 were closely related but differed in their antibiotic and phage susceptibility profiles. Early isolates were not susceptible to the phage used for therapy, while later isolates, including two isolates collected during phage therapy, were susceptible. Susceptibility to the phage used for therapy was correlated with differences in O-antigen profiles of an early versus a late isolate. CONCLUSIONS: This case of clinical failure of nebulized phage therapy highlights the limitations, unknowns, and challenges of phage therapy for resistant infections.

Clinical outcomes of therapeutic leukapheresis in acute promyelocytic leukemia: A single-center retrospective cohort study.

BACKGROUND: In acute promyelocytic leukemia (APL), increased cell burden in the peripheral blood due to either the disease itself or early treatment with all-trans retinoic acid could cause hyperleukocytosis (HL) before induction chemotherapy. However, therapeutic leukapheresis has seldom been used because of concerns of subsequent coagulopathy after this invasive procedure. The aim of this study was to evaluate the effects of leukapheresis in APL, especially for efficacy and safety. METHODS: We retrospectively analyzed newly diagnosed patients with APL from January 2009 to March 2022. Among 323 patients, 85 had white blood cell count above 40 × 109/L before induction chemotherapy. Thirty-nine patients were initially treated with leukapheresis, whereas the other 46 were not. Clinical and laboratory parameters between these groups were compared. RESULTS: There was a trend toward favorable 30-day survival rate for the leukapheresis group compared with the non-leukapheresis group (76.9% and 67.4%; P = 0.24). The complications including subsequent intensive unit care (P = 0.23), severe hemorrhagic events (P = 0.13) showed no significant differences between the two groups. The patients were divided into subcohorts, and the survival rates of the leukapheresis and non-leukapheresis groups were 92.3% (95% confidence interval [CI], 77.8%-100.0%) versus 58.3% (95% CI, 38.6%-78.1%) (P = 0.03) in "sequential HL" and 76.7% (95% CI, 61.5%-91.8%) versus 54.8% (95% CI, 37.3%-72.4%) (P = 0.03) in "symptomatic HL," respectively. Moreover, in the "sequential HL" subcohort, the cumulative incidence of differentiation syndrome and following adverse events were significantly lower in the leukapheresis group. CONCLUSIONS: In APL with "sequential HL" or "symptomatic HL" from either the disease itself or the effect of all-trans retinoic acid, therapeutic leukapheresis could be applied to reduce leukemic cell burden without significant risks.

Benefits of dexamethasone on early outcomes in patients with acute myeloid leukemia with hyperleukocytosis: a propensity score matched analysis.

Hyperleukocytosis is associated with a significant early mortality rate in patients with acute myeloid leukemia (AML). To date, no controlled trial has ever evaluated a strategy to reduce this risk, and the initial management of these patients remains heterogeneous worldwide. The aim of the present study was to evaluate the influence of a short course of intravenous dexamethasone on the early outcomes of patients with hyperleukocytic AML with white blood cell (WBC) count above 50 × 109/L. Clinical and biological data of all consecutive patients (1997-2017) eligible for intensive chemotherapy from a single center were retrospectively collected. A total of 251 patients with a median age of 51 years and a median WBC count of 120 × 109/L were included, 95 of whom received dexamethasone. Patients treated with dexamethasone had higher WBC count and a more severe disease compared with those who did not, and they presented more often with leukostasis and hypoxemia, resulting in a more frequent need for life-sustaining therapies (p < 0.001). To account for these imbalances, patients were compared after adjusting for a propensity score, which included all variables with a prognostic influence in the overall cohort. In the matched cohort, dexamethasone was associated with lower early death (OR = 0.34, p = 0.0026) and induction failure rate (OR = 0.44, p = 0.02) and better overall survival (HR = 0.60, p = 0.011), with no impact on relapse risk (cHR = 0.73, p = 0.39). The overall survival benefit was confirmed among all tested subgroups. This study suggests that dexamethasone administration is safe and associated with a lower risk of induction mortality in patients with hyperleukocytic AML and deserves prospective evaluation.

Long-lasting leukocytosis in patients with schizophrenia treated with clozapine after electroconvulsive therapy : ECT stabilizes white blood cell count.

INTRODUCTION: The present study was conducted to investigate the possible hematologic impact of long-term electroconvulsive therapy (ECT) in patients with drug-resistant schizophrenia and receiving clozapine therapy. SUBJECTS AND METHODS: In this retrospective study, clinical charts of 57 hospitalized patients with schizophrenia who required clozapine therapy because of active psychotic symptoms resistant to other antipsychotics were examined. For 18 who underwent ECT, the first assessment was conducted at the end of that therapy (average two months after start, 7.68 sessions) and the second two months later. As for the 39 patients who did not undergo ECT, the first and second assessment points were at two and four months, respectively, after a randomly chosen time point. RESULTS: Multiple regression analysis revealed that modified ECT (m-ECT) (ß = 0.346, p = 0.005), gender (males showed greater increase) (ß = 0.273, p = 0.023), and disease duration (longer associated with greater increase) (ß = 0.258, p = 0.033) were correlated with a change in white blood cell (WBC) count (ΔR2 = 0.277, p < 0.001) at the first assessment point. At the second assessment point, multiple regression analysis showed that m-ECT (ß = 0.262, p = 0.039), gender (males showed greater increase) (ß = 0.264, p = 0.036), and disease duration (longer associated with greater increase) (ß = 0.234, p = 0.068) were again correlated with changed WBC count (ΔR2 = 0.203, p < 0.007). DISCUSSION: An increase in leukocytes may have a protective influence against the adverse myelosuppressive effects of clozapine. However, a simple mobilization of leukocytes from bone marrow to peripheral circulation may not enhance the immune system, leading to only a masking of the effects of a potential immuno-insufficient state in the treated patient. In either case, should leukocytosis be induced and then remain for an extended period, hematologists, as well as psychiatrists involved in electroconvulsive intervention for clozapine-treated patients, must keep this factor in mind.

Nontuberculous Mycobacterial Infections Associated With Left Ventricular Assist Devices in 3 Patients.

Durable left ventricular assist devices (LVADs) provide circulatory support in patients with end-stage heart failure; however, complications include infection of the driveline exit site. Nontuberculous mycobacterial infections are rare in patients with LVADs, but they should be considered in those who have undergone device exchanges and have bacterial infections with driveline exit-site discharge but no fever or leukocytosis. We reviewed the charts of patients who had an LVAD implanted at our institution from January 2009 through December 2019, to identify those with a device-related nontuberculous mycobacterial infection. Collected data included patient demographics, premorbid conditions, infection type, previous device complications, treatment, and outcomes. We identified infections in 3 patients (mean age, 41 yr): Mycobacterium abscessus in 2 and M. chimaera in 1. All had a HeartMate II device and had undergone device exchanges for pump thrombosis or for driveline fault or infections. All presented with driveline exit-site discharge without fever or leukocytosis. The mean time between initial device implantation and diagnosis of a nontuberculous mycobacterial infection was 55 months. All 3 patients were treated with antibiotics and underwent localized surgical débridement; one underwent an additional device exchange. The M. abscessus infections disseminated, and both patients died; the patient with M. chimaera infection continued to take suppressive antibiotics. Nontuberculous mycobacterial infections are associated with high morbidity and mortality rates, warranting prompt diagnosis and treatment.

Effect of interleukin-1 blockade with anakinra on leukocyte count in patients with ST-segment elevation acute myocardial infarction.

Leukocytosis is a common finding in patients with ST elevation myocardial infarction (STEMI) and portends a poor prognosis. Interleukin 1-ß regulates leukopoiesis and pre-clinical studies suggest that anakinra (recombinant human interleukin-1 [IL-1] receptor antagonist) suppresses leukocytosis in myocardial infarction. However, the effect of IL-1 blockade with anakinra on leukocyte count in patients with STEMI is unknown. We reviewed the white blood cell (WBC) and differential count of 99 patients enrolled in a clinical trial of anakinra (n = 64) versus placebo (n = 35) for 14 days after STEMI. A complete blood cell count with differential count were obtained at admission, and after 72 h, 14 days and 3 months. After 72 h from treatment, anakinra compared to placebo led to a statistically significant greater percent reduction in total WBC count (- 35% [- 48 to - 24] vs. - 21% [- 34 to - 10], P = 0.008), absolute neutrophil count (- 48% [- 60 to - 22] vs. - 27% [- 46 to - 5], P = 0.004) and to an increase in absolute eosinophil count (+ 50% [0 to + 100] vs. 0% [- 50 to + 62], P = 0.022). These changes persisted while on treatment at 14 days and were no longer apparent at 3 months after treatment discontinuation. We found that in patients with STEMI IL-1 blockade with anakinra accelerates resolution of leukocytosis and neutrophilia. This modulation may represent one of the mechanisms by which IL-1 blockade improves clinical outcomes.

Prognostic impact of neutrophilia and lymphopenia on survival in anal cancer treated with definitive concurrent chemoradiotherapy: a retrospective multicenter study.

PURPOSE: This study evaluated the prognostic value of leukocyte, lymphocyte, and neutrophil counts in anal cancer patients undergoing concurrent chemoradiotherapy (CCRT). METHODS: Multi-institutional retrospective data review included 148 non-metastatic anal cancer patients treated with definitive CCRT with 5-fluorouracil plus mitomycin C between the year 2001 and 2019. The median radiation dose to the primary tumor was 54 Gy with a median pelvic dose of 45 Gy. Median follow-up duration was 56 months, and complete blood cell counts were analyzed from baseline to 1 year after the completion of radiotherapy. RESULTS: Although most patients showed a normal number of blood cells before treatment, 6.1% and 4.1% of patients showed leukocytosis (> 10,000/µl) and neutrophilia (> 7500/µl), respectively. After the initiation of treatment, seven patients (4.7%) displayed grade 4 lymphopenia (< 200/µl) at 1 month. Patients with initial leukocytosis showed inferior progression- and locoregional progression-free survival, and neutrophilia was a prognostic factor in all survival outcomes. Grade 4 lymphopenia at 1 month was also significantly associated with overall, progression-, and distant metastasis-free survival. On multivariate analyses, baseline neutrophilia was associated with 56.8-, 22.6-, 10.7-, and 23.0-fold increased risks of death, disease relapse, locoregional progression, and distant metastasis, respectively. Furthermore, lymphocytes < 200/µl at 1 month was linked to 6.8-, 5.4-, and 6.3-fold increased risks for death, disease relapse, and distant metastasis, respectively. CONCLUSION: The number of leukocytes, lymphocytes, and neutrophils readily acquired from routine blood tests before and during treatment could be an independent prognostic factor of survival in patients with anal cancer.

Leukocytosis Associated with Clozapine Treatment: A Case Series and Systematic Review of the Literature.

BACKGROUND AND OBJECTIVES: Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia. Despite its superior efficacy profile as compared with other antipsychotics, clozapine remains underutilized. Clozapine monitoring systems clearly describe the proposed management of clozapine-induced neutropenia; however, no specific mention is made of how to interpret neutrophilic leukocytosis, despite that being a relatively frequent finding. Prescribers unfamiliar with this molecule may misjudge its clinical significance, potentially leading to untimely treatment interruption. Here, we systematically review the literature on the risk of neutrophilic leukocytosis during clozapine treatment, and describe eight additional cases among our patient cohort. MATERIALS AND METHODS: We performed a systematic review of the literature on PubMed and Embase using the PRISMA 2020 guidelines, and selected all original reports describing either (1) the prevalence of neutrophilic leukocytosis during clozapine treatment, or (2) the clinical significance of neutrophilic leukocytosis. We described eight additional cases of neutrophilic leukocytosis during clozapine treatment while attending an outpatient psychiatric clinic. RESULTS: Our research ultimately yielded the selection of 13 articles included in this systematic review. The case series highlighted the presence of stable and clinically unremarkable neutrophilia during a follow-up ranging from one to ten years. CONCLUSIONS: Existing evidence indicates that leukocytosis associated with clozapine treatment can be considered as an asymptomatic and benign condition, suggesting that no change in clozapine treatment is needed upon its detection.

Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo.

Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein α-subunits resulting in increased cAMP signaling. Here, a role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is demonstrated. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing intracellular PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.

Abscés cervical profund associat a col·locació de mascareta laríngia / Absceso cervical profundo asociado a la colocación de mascarilla laríngea / Deep neck abscess associated to the placement of a laryngeal mask

INTRODUCCIÓ: Els abscessos parafaringi I retrofaringi són infeccions profundes del coll que solen associar-se a l'antecedent d'infecció de vies respiratòries altes. Ocasionalment poden ser causats per traumatismes com els que comporten algunes manipulacions mèdiques, per exemple, la col·locació de mascareta laríngia, molt utilitzada en cirurgia pediàtrica. CAS CLÍNIC: Es presenta el cas d'una nena de 6 anys amb torticoli de 8 dies d'evolució I febre de 24 hores, sense cap altra simptomatologia. La pacient havia estat intervinguda quirúrgicament sota anestèsia general amb col·locació de mascareta laríngia 36 hores abans de l'inici del quadre, sense incidències. En l'exploració, destaca una contractura cervical bilateral amb flexió del cap a la dreta, I a l'analítica es troba leucocitosi amb predomini de neutròfils I augment de la proteïna C reactiva. Es fa una ressonància magnètica cervical en què s'observa un abscés d'extensió parafaríngia I retrofaríngia, I s'indica una punció percutània ecoguiada de l'àrea abscessificada, que resulta positiva per a S. pyogenes. S'ingressa la pacient amb antibioteràpia endovenosa I s'aconsegueix la millora clínica I radiològica de l'abscés. COMENTARIS: Els abscessos cervicals profunds s'han de considerar davant de simptomatologia obstructiva I inflamatòria de la via aèria I el tracte digestiu superior, I símptomes locals o dolor al moviment cervical. El diagnòstic es basa en les troballes radiològiques, analítiques I microbiològiques, I cal instaurar antibioteràpia endovenosa empírica amb cobertura per a estafilococs, estreptococs I anaerobis. Tot I que aquests abscessos en la majoria de casos són secundaris a l'extensió d'infeccions del tracte respiratori superior, hi ha altres causes que cal considerar

INTRODUCCIÓN: Los abscesos retrofaríngeo y parafaríngeo son infecciones profundas del cuello que suelen asociarse al antecedente de infección de vías respiratorias altas. Ocasionalmente pueden ser causados por traumatismos como los que resultan de algunos procedimientos médicos, por ejemplo, la colocación de la mascarilla laríngea, muy utilizada en cirugía pediátrica. CASO CLÍNICO: Se presenta el caso de una niña de 6 años con tortícolis de 8 días de evolución y fiebre de 24 horas, sin otra sintomatología. La paciente había sido intervenida quirúrgicamente bajo anestesia general con colocación de mascarilla laríngea 36 horas antes del inicio del cuadro, sin incidencias. A la exploración, destaca una contractura cervical bilateral con flexión de la cabeza hacia la derecha, y en la analítica se encuentra leucocitosis con predominio neutrofílico y ligero aumento de proteína C reactiva. Se realiza una resonancia magnética cervical donde se observa un absceso de extensión parafaríngea y retrofaríngea, y se practica una punción percutánea ecoguiada de la zona abscesificada, que resulta positiva para S. pyogenes. La paciente ingresa con antibioterapia endovenosa y se consigue mejoría clínica y radiológica del absceso. COMENTARIO: Los abscesos cervicales profundos deben considerarse ante sintomatología obstructiva e inflamatoria de la vía aérea y del tracto digestivo superior, y síntomas locales o dolor al movimiento del cuello. El diagnóstico se basa en los hallazgos radiológicos, analíticos y microbiológicos y se debe instaurar antibioterapia endovenosa empírica con cobertura para estafilococos, estreptococos y anaerobios. Aunque en la mayoría de casos estos abscesos son secundarios a la extensión de infecciones del tracto respiratorio superior, existen otras causas que deben considerarse

INTRODUCTION: Retropharyngeal and parapharyngeal abscesses are deep neck infections that are usually associated with superior airway infections in children. However, they could also be caused by injuries secondary to medical procedures such as the placement of laryngeal masks, which are frequently used in pediatric surgery. CASE REPORT: A 6-year-old female presented to the emergency room with an 8-day history of torticollis and 24 hours of fever with no other associated symptomatology. She had undergone surgery under general anesthesia using a laryngeal mask 36 hours prior, without immediate complications. In the physical examination, the patient had bilateral cervical contracture with right bending. The blood examination showed leukocytosis with predominance of neutrophils and increase of C-reactive protein. Magnetic resonance imaging showed an abscess with parapharyngeal and retropharyngeal extension, and a percutaneous ultrasound-guided puncture of the abscessed area was performed, which resulted positive for S. pyogenes. The patient received intravenous antibiotic therapy and achieved clinical and radiological resolution of the abscess. COMMENTS: Deep neck abscesses should be considered in children with obstructive and inflammatory symptomatology of the airway and upper digestive tract and also local symptoms as neck pain. Diagnosis is based on radiological, analytical and microbiological findings and empirical intravenous antibiotics, with coverage for staphylococcus, streptococcus and anaerobics. Although in most cases these abscesses are secondary to the spread of upper respiratory tract infections, other causes should be considered

Infection of arteriovenous fistula for hemodialysis: An uncommon etiology / Infección de fístula arteriovenosa protésica para hemodiálisis de causa inusual

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The Effect of TLR4 Blockade on Some Indicators of Systemic Inflammatory Response to Proteus mirabilis LPS in Rats.

The effects of TLR4 blocker on blood cell morphology, concentrations proinflammatory cytokines, and functional state of the liver and kidneys were studied in outbred male rats (n=60) after intravenous injection of 20 mg/kg LPS isolated from opportunistic Proteus mirabilis strain ATCC 51393. TLR4 blocker TLR4-IN-C34 was injected intravenously in a dose of 1 mg/kg/day over 3 days. Systemic inflammatory reaction induced by LPS was characterized by elevation of serum TNFα, IL-1ß, IL-6, erythrocyte sedimentation rate, leukocytosis, and thrombocytosis. Increased activity of hepatocyte enzymes (ALT, alkaline phosphatase, and lactate dehydrogenase), retention of nitrogen metabolites (urea and creatinine), elevated content of protein oxidation products, and enhanced protein catabolism were also observed. Administration of TLR4 blocker reduced parameters of inflammatory reaction and prevented the development of hypercatabolic syndrome; endotoxicosis and kidney function indicators approached the normal levels.

Delayed Granulocyte Colony-Stimulating Factor (G-CSF) Administration after Chemotherapy Reduces Total G-CSF Doses without Affecting Neutrophil Recovery in a Randomized Clinical Study in Children with Solid Tumors.

The use of G-CSF after myelotoxic chemotherapy accelerates neutrophil recovery reducing the risk of febrile neutropenia. Current guidelines recommend initiating G-CSF 24 hours after myelotoxic chemotherapy. However, the optimal timing of post-chemotherapy G-CSF administration has not been elucidated. Our previous work in murine models demonstrated that the reappearance of myeloid progenitors does not occur in bone marrow until 3-4 days after completion of chemotherapy suggesting that delayed G-CSF administration may be equally efficacious compared to current practice. We conducted a prospective, randomized, crossover study to compare the absolute neutrophil count (ANC) recovery after chemotherapy and a delayed G-CSF administration to a standard G-CSF administration schedule with early G-CSF start. A total of 21 children with solid tumors who received 2 identical cycles of myelotoxic chemotherapy were randomized to start receiving G-CSF either 24 hours after completion of chemotherapy or on the day that their ANC dropped below 1,000/mm3. There was no significant difference in the time to neutrophil recovery (ANC > 1,000/mm3 post nadir) between the two G-CSF administration schedules: 16.0 ± 0.5 days in the standard group compared to 16.7 ± 0.4 days in the delayed group (p = 0.36). The total number of G-CSF doses given, however, was significantly less in the delayed group: 6.7 ± 0.6 compared to 10.5 ± 0.6 doses in the standard group (p < 0.0001). Our data show that a delayed administration of post chemotherapy G-CSF resulted in a significant reduction in the number of G-CSF injections without compromising the G-CSF effects on neutrophil recovery.