Abdominal and pelvic actinomycosis due to longstanding intrauterine device: a slow and devastating infection

Actinomycosis is a chronic or subacute bacterial infection characterized by large abscess formation, caused mainly by the gram-positive non-acid-fast, anaerobic, or microaerophilic/capnophilic, obligate parasites bacteria from the Actinomyces genus. Although pelvic inflammatory disease is an entity associated with the longstanding use of intrauterine devices (IUDs), actinomycosis is not one of the most frequent infections associated with IUDs. We present the case of a 43-year-old female patient who was referred to the emergency facility because of a 20-day history of abdominal pain with signs of peritoneal irritation. Imaging exams revealed collections confined to the pelvis, plus the presence of an IUD and evidence of sepsis, which was consistent with diffuse peritonitis. An exploratory laparotomy was undertaken, and a ruptured left tubal abscess was found along with peritonitis, and a huge amount of purulent secretion in the pelvis and abdominal cavity. Extensive lavage of the cavities with saline, a left salpingo-oophorectomy, and drainage of the cavities were performed. The histopathological examination of the surgical specimen revealed an acute salpingitis with abscesses containing sulfur granules. Therefore, the diagnosis of abdominal and pelvic actinomycosis was made. The postoperative outcome was troublesome and complicated with a colocutaneous fistula, which drained through the surgical wound. A second surgical approach was needed, requiring another extensive lavage and drainage of the recto-uterine pouch, plus the performance of a colostomy. Broad-spectrum antibiotics added to ampicillin were the first antimicrobial regimen followed by 4 weeks of amoxicillin during the outpatient follow-up. The patient satisfactorily recovered and is already scheduled for the intestinal transit reconstitutio

Hemophagocytic lymphohistiocytosis of indeterminate cause: a fatal adult case

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon life-threatening disorder characterized by wide spread non-neoplastic proliferation and inappropriate activation of mature macrophages resulting in hypercytokinemia.This uncontrollable and ineffective systemic immune response causes fever, hepatosplenomegaly, cytopenias and subsequently multiorgan failure. The authors report a case of a 41-year-old male patient with a 30-day history of weight loss, fever, icterus, hepatomegaly, and cytopenias. The diagnosticworkup disclosed hypertriglyceridemia, hypofibrinogenemia, and elevated ferritin. Bone marrow examination and clinical course raised the suspicion of HLH and treatment was started with high-dose corticosteroids and immune globulin. The patient underwent multi-organ failure and expired after 58 days ofhospitalization. The autopsy finding included massive bone marrow infiltration by non-neoplastic histiocytes, many of them showing hemophagocytosis, which immunohistochemical study revealed diffuse CD68-positive histiocytes, which were negative for S100 protein. Hemophagocytosis was also observedin the lungs, lymph nodes and liver. The immediate cause of death was attributed to a massive intestinal bleeding due to extensive ischemic necrosis at the duodenum/jejunal transition area.nul

Embelin potentiates venetoclax-induced apoptosis in acute myeloid leukemia cells

Acute myeloid leukemia (AML) belongs to a group of hematological cancer whose relapse cases are often associated with chemoresistance that impairs treatment success and contributes to a poor outcome. For this reason, there is an urgent need for the development of new therapeutic strategies. Herein, we explore the combination of venetoclax, a BCL2 inhibitor, and embelin, an XIAP inhibitor, in the AML cell lines. Combinatory treatment of venetoclax and embelin potentiated cytotoxic effects of these drugs, demonstrating that both in combination present lower IC50 values than single treatment of either venetoclax or embelin alone in both cell lines analyzed. The combinatory treatment further increased the apoptosis-inducing properties of both compounds. Computer simulations suggest that embelin binds to both BIR2 and BIR3 domains of XIAP, reinforcing this inhibitory apoptosis protein as an embelin target. Although all AML cell lines presented similar basal levels of XIAP, the combinatory treatment effectively inhibited XIAP expression in OCI-AML3 cells. In conclusion, the inhibition of both apoptosis inhibitory players, BCL2 and XIAP, by venetoclax and embelin, respectively, potentiated their cytotoxic effects in AML cell lines.The authors want to express their acknowledgements to Prof. Dr. Eduardo Magalhaes Rego (University of Sao Paulo, Ribeirao Preto, Brazil) for providing leukemia cell lines. We are also grateful for the embelin HPLC analysis by Prof. Marcelo Jose Pena Ferreira (IB-USP). This work was supported by Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazil, under processes 2019/23864-7, 2018/ 06522-2, 2017/09022–8, and 2015/17177–6. This study was financed in part by the Coordenaçao de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.Postprint (author's final draft

Diffuse large B-cell lymphoma presenting in the leukemic phase

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma comprising a heterogeneous group of disorders with variable histological and clinical behavior. Although other lymphomas may present in the leukemic phase more frequently, this appearance is unusually observed among DLBCL cases. Diagnosing lymphoma is not always easy, and the patient’s clinical status quite often may hamper invasive procedures for diagnosis pushing the clinician to look for alternatives to reach the nearest possible accurate diagnosis. The authors report the case of a middle-aged man who presented the history of malaise, weight loss, and low-grade fever. The peripheral blood count showed leukocytosis with the presence of blasts and thrombocytopenia. The cytological morphology and immunophenotyping of the peripheral blood and bone marrow aspirate, as well as the bone marrow biopsy accompanied by a thorough immunohistochemical analysis, rendered the diagnosis of DLBCL in the leukemic phase. The patient was prescribed R-CHOP with a favorable outcome. Intra-abdominal lymph node biopsy was avoided because of the patient’s critical medical condition. The authors highlight this rare form of presentation of DLBCL as well as the combination of peripheral blood, bone marrow aspirate, and bone marrow biopsy for reaching the diagnosis in cases were a lymph node sample is unavailable for the diagnostic work-u

Tributo ao centenário da Síndrome de Waterhouse-Friderichsen: relato de caso

The Waterhouse-Friderichsen Syndrome was first reported by Rupert Waterhouse exactly 100 years ago on March 4th, 1911. It is an acute infectious disease that generally progress to a lethal outcome despite the adoption of all available resources of an intensive therapy unit. We describe an illustrativecase of meningococcal meningitis C. This report details the clinical, pathological and therapeutic features of a patient of 3 years and 4 months who had a fulminating evolution, despite adherence to updated recommendations for the treatment of pediatric septic shock. We stress the little change in clinicaland pathological aspects of Waterhouse-Friderichsen Syndrome during the last 100 years, despite tremendous advances in therapy and technology of the pediatric intensive care.A síndrome de Waterhouse-Friderichsen teve o relato pioneiro de Rupert Waterhouse há exatamente 100 anos em 4 de março de 1911. É uma síndrome infecciosa aguda de evolução catastrófica que requer a utilização de todos os recursos disponíveis de terapia intensiva e geralmente evolui para o êxito letal.Nós descrevemos um caso ilustrativo de meningite meningocócica C que ilustra aspectos clínicos, terapêuticos e anatomopatológicos de uma criança de 3 anos e 4 meses atendida em um Hospital Universitário com evolução fatal, apesar da aderência às recomendações vigentes atualizadas para o tratamento do choque séptico pediátrico. Salientamos a pouca mudança no aspecto clínico e anatomopatológicoda síndrome de Waterhouse-Friderichsen nos últimos 100 anos, apesar da enorme evolução terapêutica e tecnológica que acompanha a terapia intensiva pediátrica

Acute erythroid leukemia: autopsy report of a rare disease

Acute erythroid leukemia (AEL) is a rare subtype of acute myeloid leukemia(AML), characterized by predominant erythroid proliferation. The 2008 WorldHealth Organization (WHO) classification of AML defined two AEL subtypes:erythroleukaemia (EL), in which erythroid precursors account for 50% or moreof all nucleated bone marrow cells and myeloblasts account for 20% or more ofthe nonerythroid cell population; and pure erythroid leukemia (PEL), in whicherythroid precursors account for 80% or more of all nucleated bone marrowcells. We report the case of an elderly female patient with wasting syndromeand pancytopenia without evidence of blasts in peripheral blood. A diagnosisof PEL was established on the basis of bone marrow biopsy findings. Thepatient died on postadmission day 20, and an autopsy was performed. Wereclassified the disease as EL on the basis of the autopsy findings, whichincluded myeloblasts accounting for more than 20% of the nonerythroid cellsin the bone marrow, as well as leukemic infiltration and myeloid metaplasia insolid organs, such as the liver, spleen, kidneys, adrenal glands, and abdominallymph nodes. A rare disease, AEL accounts for less than 5% of all AMLs and ispractically a diagnosis of exclusion. Autopsy reports of AEL are extremely rarein the literature. We demonstrate that in the case reported here, leukemia cellstended to infiltrate solid organs with myeloid metaplasia. Our findings alsoshow that a larger neoplastic bone marrow sample is crucial to the correctdiagnosis of EL, which is based on morphological and quantitative criteria

Detection and characterization of Bacillus cereus isolated from the dialysis fluid

In this study, B. cereus was detected in dialysis fluids within international parameters (ultrapure – maximum limit of 0.1 CFU/mL for heterotrophic bacteria count) by analyzing the pellet obtained through the centrifugation method. We also investigated the ability of the B. cereus isolate to form a biofilm at different temperatures, the production of virulence factors, and the susceptibility to commercial antimicrobial agents. This study demonstrated a high ability of B. cereus to persist in the hemodialysis system, which can be explained by its broad ability to produce a biofilm at 25 °C, its relevant production of virulence factors, such as β-hemolysin, lecithinase and cereulide, and its important resistance pattern to antimicrobial drugs. In conclusion, these new findings expand the understanding that this microorganism should not be neglected and new methods for tracking it should be considered

Accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C

OBJECTIVES: Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. METHODS: We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. RESULTS: A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION: Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4

Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient’s 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profil

Application of polyetheretherketone (PEEK) posts: evaluation of fracture resistance and stress distribution in the root: in vitro and finite element analyses

Abstract To evaluate the feasibility of using a milled polyetheretherketone (PEEK) post and core in endodontically treated teeth with or without a ferrule. Sixty bovine tooth roots were endodontically treated followed by cementation of intraradicular retainers (IR), according to each experimental group: a) non-ferrule glass fiber post (f0FP); b) 2-mm-ferrule glass fiber post (f2FP); c) non-ferrule resized glass fiber post (f0PR); d) 2-mm-ferrule resized glass fiber post (f2PR); e) non-ferrule PEEK post and core (f0PPC); and f) 2-mm-ferrule PEEK post and core (f2PPC). Metal crowns were made and cemented. A periodontal ligament was simulated using polyether. A force was applied to the palatine portion of each sample at 45°, until fracture. Fracture resistance data were submitted to two-way ANOVA and Tukey’s test (α = 0.05). Three-dimensional digital models were developed to calculate the tensions formed in the root using finite element analysis. Models of glass fiber posts and PEEK posts and cores were evaluated with or without a ferrule. The results were analyzed by the Mohr-Coulomb criterion. The type of IR was not influenced by fracture strength (p = 0.243). There were significant statistical differences among the remaining factors. Ferrule groups had greater fracture resistance, and the failure mode of teeth with a ferrule was more catastrophic than the non-ferrule group. A ferrule increases fracture resistance and influences failure mode; the PEEK post and core did not modify the biomechanics of endodontically treated teeth, and resembled the glass fiber post results. The crack initiation point differed between the ferrule and non-ferrule groups