Search

Introdução: A tricoleucemia (TL) ou leucemia de células pilosas (LCP) é uma doença linfoproliferativa que corresponde a cerca de 2% das leucemias linfoides, sendo caracterizada por sintomas relacionados à citopenias importantes e esplenomegalia. Sua prevalência é maior em homens (4:1) na faixa etária de 50-60 anos. O diagnóstico se baseia na avaliação morfológica de esfregaços de sangue periférico, na biópsia de medula óssea com imuno-histoquímica, assim como no aspirado da medula óssea com imunofenotipagem. O tratamento da TL é reservado para pacientes sintomáticos ou com citopenias significativas. São utilizados análogos da purina, como a Cladribina e a Pentostatina no tratamento de primeira linha e a esplenectomia, tratamento antigo, pode ainda ser considerada em pacientes com hiperesplenismo. O diagnóstico diferencial inclui outras neoplasias linfoproliferativas de células B, incluindo linfoma de zona marginal esplênico (LZME), linfoma folicular, leucemia linfocítica crônica entre outras doenças linfoproliferativas. A imuno-histoquímica (IH) e imunofenotipagem (IF) da medula em geral diferenciam as doenças acima. Objetivo: Relatar o caso de um paciente com doença linfoproliferativa de células B de difícil diagnóstico que foi definido após esplenectomia. Relato do caso: Homem, de 35 anos, encaminhado para investigação de adinamia, esplenomegalia há 8 meses e pancitopenia desde o início de 2020 com Hb 8,8 g/dL; L 2000/mm3 (Sg 1540/mm3 e Li 300/mm3) e P 27.000/mm3. Realizado, em outro serviço, mielograma sugestivo de neoplasia linfoide B e biópsia de medula óssea que evidenciou medula óssea hipocelular com possível infiltração linfoproliferativa crônica. Encaminhado ao nosso serviço em 05/21, sendo repetidos o mielograma (linfocitose) e a biópsia de medula óssea (celularidade de 70%, trama reticulínica grau II e linfocitose B difusa de pequenas células). IH com BCL2, CD10, CD20 positivos e DBA44 e anexina negativos. IF com linfócitos B anômalos monoclonais com fenótipo sugestivo de Hairy Cell (CD25 + / CD103 parcial). Pela piora da pancitopenia, possivelmente por hiperesplenismo e pela falta de diagnóstico definitivo, foi realizada esplenectomia que prontamente resolveu a pancitopenia e confirmou o diagnóstico de tricoleucemia. IH 10/21 com Anexina 60%, CD25 70%, PAX5 90%, BCL2+, CD10+ e CD20+. Atualmente, o paciente está assintomático sem citopenias. 06/23 (22 meses) Hb 15,2 g/dL L 8100/mm3 e P 314.000/mm3. Discussão e conclusão: A LCP é uma neoplasia linfoproliferativa crônica de células B. Em cerca de 80% dos casos é detectada a presença de mutacao somática do gene para a proteina-quinase BRAF, exame não disponível para o paciente relatado. O perfil IF demonstra positividade para CD11c, CD19, CD25, CD103 e CD123. A biópsia de medula óssea na LCP costuma apresentar fibrose leve e infiltrado celular difuso. O paciente em questão, apresentava positividade para CD25 e CD103 na IF, quadro clínico e presença de células com fenótipo sugestivo para células pilosas, mas não houve confirmação pela biópsia ou imunofenotipagem. Pela falta de confirmação diagnóstica e pelo hiperesplenismo optou-se pela esplenectomia que resultou no diagnóstico, resolveu a pancitopenia e pode manter uma remissão prolongada da tricoleucemia.

Introduction: Mass screening for SARS-CoV-2 using nasopharyngeal swabs (NPS) is costly, uncomfortable for patients, and increases the chance of virus exposure to health care workers. Therefore, this study focused on determining if self-collected unpreserved saliva can be an effective alternative to NPS collection in COVID-19 surveillance., Materials and Methods: In this study, patients being tested for SARS-CoV-2 using NPS were asked to provide a saliva sample to compare their results. NPS samples were evaluated for SARS-CoV-2 using BioFire® FilmArray® Torch® or Cepheid® GeneXpert® systems while saliva samples were evaluated using an in-house developed reverse transcriptase polymerase chain reaction (RT-PCR) which targeted the Envelope (E) and Nucleocapsid (N) genes., Results: Detection of SARS-CoV-2 using self-collected saliva was found to be only slightly less accurate (<5%) than testing using NPS. In addition, initial saliva RT-PCR identified 27 positive subjects, 18 of which provided amplicons sufficient for confirmatory sequencing. The sequencing data showed a genetic shift in the virus within our population sometime between 22 June and July 8, 2021 from Alpha to Delta variant., Conclusions: The saliva sample collection method identifies the E gene in SARS COVID-2 samples which provides an alternative specimen source to the NPS. This identifies the S gene and ORF1ab. Saliva collection is more convenient to the patient, yields comparable results to NPS collection, and potentially increases Covid-19 surveillance., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Context.—: Metastatic mucinous tumors present a diagnostic challenge for pathologists as tumor histomorphology is often nonspecific and optimal immunoprofiles are still under investigation., Objective.—: To present a head-to-head comparison of special AT-rich sequence-binding protein 2 (SATB2) and caudal type homeobox 2 (CDX2) expression in a diverse array of primary mucinous tumors., Design.—: SATB2 and CDX2 immunohistochemical stains were performed on whole sections from 44 mucinous colorectal carcinomas and 175 noncolorectal mucinous tumors. A nuclear scoring system measuring intensity (0-3+) and percentage staining (0 = <5%, 1 = 5%-49%, 2 = ≥50%) was implemented, producing an additive histologic score (H-score)., Results.—: SATB2 demonstrated acceptable accuracy at low to moderate expression levels (H-scores of 1-4). With these H-score cutoffs, overall accuracy was greater than 90%. In contrast, CDX2's accuracy rivaled that of SATB2 only at an H-score of 5 (89.0%), as its specificity suffered at lower expression levels (<70.0% at H-scores of 1-4). Using a moderate H-score cutoff of 3 or higher, significant differences for both sensitivity and specificity were identified between SATB2 and CDX2 ( P = .01 for sensitivity and P < .001 for specificity), though these stains were near equivalent when each was interpreted as positive at its respective optimal H-score (SATB2 ≥ 3 and CDX2 = 5)., Conclusions.—: SATB2 is a more accurate marker of colorectal origin across a variety of expression levels compared with CDX2 when applied to mucinous tumors from a host of primary sites. However, these stains are near equivalent when each is interpreted at its optimal expression level.

Special AT-rich sequence-binding protein 2 (SATB2) is an accurate marker for conventional colorectal carcinoma (CRC), although its sensitivity and specificity in mucinous tumors from the colon and other sites remains unknown. The objective of this study is to evaluate the accuracy of SATB2 expression detected by immunohistochemical assay, as a marker of primary CRC in mucinous adenocarcinomas. SATB2 immunohistochemical stains were performed on whole sections from 63 conventional CRCs (controls), 47 mucinous CRCs (mCRC), and 182 noncolorectal mucinous tumors. SATB2 intensity was scored as 1 to 3 based on the estrogen receptor/progesterone receptor grading system, and the percent positive cells was scored in broad categories as follows: 0 (negative)≤5%, 1=5% to 49%, 2≥50%. An optimal sensitivity/specificity pairing (83% and 95%, respectively) was achieved in the mCRCs when the additive intensity and percent score was ≥3 (ie, intensity score+percent score=total score). Defining this total score (histologic score/"H score") as a "positive" result, the sensitivity of SATB2 for conventional CRC was 98% (62/63) versus 83% (39/47) for mCRCs (P=0.02); whereas 5% (9/182) of all noncolorectal mucinous tumors were considered positive. SATB2 especially demonstrated reduced specificity when applied to mucinous gastroesophageal and breast carcinomas, which showed significant expression in 27% and 9% of cases, respectively. In summary, SATB2 is a less sensitive marker of colorectal origin in mCRC compared with conventional CRC and shows significantly reduced specificity in mucinous gastroesophageal and breast primaries.

HDR syndrome is a rare autosomal dominant disorder caused by mutations in the GATA3 gene and characterized by hypoparathyroidism, sensorineural deafness and renal abnormalities. Here we report a Brazilian family, from which the proband, his mother and his grandfather were diagnosed with bilateral sensorineural hearing loss. Molecular screening of the GJB2, GJB6 and MTRNR1 genes in the proband showed no alterations; however, whole exome sequencing detected a heterozygous mutation, c.1099C > T (p.Arg367*), in the GATA3 gene. Segregation analyses showed that the mother also had the mutation, but not the grandparents, hence indicating a different hearing impairment type for the grandfather. Paternity test of the mother of the proband confirmed that she has a de novo mutation. Furthermore, HDR syndrome was confirmed with new clinical evaluations showing right kidney agenesis in the proband. This is the first study reporting only deafness and renal abnormalities as symptoms of the p.Arg367* mutation in the GATA3 gene, and also the sixth HDR syndrome case in the world, and the first on the American continent. Together with other reported cases, this study highlights the variability of HDR syndrome symptoms in individuals with the p.Arg367* mutation, emphasizing the importance of molecular analyses for correct diagnosis.

The functional characterisation of thousands of Trypanosoma cruzi genes remains a challenge. Reverse genetics approaches compatible with high-throughput cloning strategies can provide the tool needed to tackle this challenge. We previously published the pTcGW platform, composed by plasmid vectors carrying different options of N-terminal fusion tags based on Gateway® technology. Here, we present an improved 1.1 version of pTcGW vectors, which is characterised by a fully flexible structure allowing an easy customisation of each element of the vectors in a single cloning step. Additionally, both N and C-terminal fusions are available with new tag options for protein complexes purification. Three of the newly created vectors were successfully used to determine the cellular localisation of four T. cruzi proteins. The 1.1 version of pTcGW platform can be used in a variety of assays, such as protein overexpression, identification of protein-protein interaction and protein localisation. This powerful and versatile tool allows adding valuable functional information to T. cruzigenes and is freely available for scientific community.

In this randomized, multicenter, observer-blind study, the efficacy, safety and tolerability of amoxycillin/clavulanate and cefaclor were compared in children with a clinical diagnosis of acute otitis media. Patients aged between 1 and 12 years received either amoxycillin/clavulanate (250 mg/62 mg t.i.d., or 125 mg/31 mg t.i.d. if aged under 6 years) or cefaclor (250 mg t.i.d., or 125 mg t.i.d. if aged under 6 years) for 7 days. The amoxycillin/clavulanate regimen was based on a dose of 20/5 mg/kg/day (representing 20 mg amoxycillin plus 5 mg clavulanic acid) in three divided doses. Patients were followed-up at the end of therapy and on days 10-12 and 38-40. At the end of the study (days 38-40), clinical success rates were 91.4% for amoxycillin/clavulanate and 78.6% for cefaclor. The difference was statistically significant (p = 0.008). After the 7 days of treatment, 3 patients (2.9%) in the amoxycillin/clavulanate group had clinical failure, compared with 18 patients (16.1%) in the cefaclor group (p < 0.001). Both treatments were well tolerated and there were no statistically significant differences between the groups in adverse event profiles. The incidence of diarrhea was low (7.0% amoxycillin/clavulanate, 8.4% cefaclor) and was generally of mild or moderate intensity. The study demonstrated that amoxycillin/clavulanate was significantly more effective clinically than cefaclor in the treatment of acute otitis media in children.

OBJECTIVE: Otitis media is the most frequently diagnosed infection in the pediatric office. Ninety per cent of the children present at least one episode of otitis media before the fifth birthday. We reviewed the literature in order to update information regarding the current definitions of acute otitis media, recurrent otitis media and otitis media with effusion, analyzing the predisposing factors, microbiology, clinical manifestations, diagnostic criteria and methods of treatment for these entities, and the relationship between otitis media and language development and learning disabilities.DATA SOURCE: Bibliographic review of an eighteen- year period (1980-1998) using Index Medicus and Medline.RESULTS AND CONCLUSIONS: More than 25 million diagnoses per year of middle ear infections are made in the United States, being responsible for rising costs of treatment. The role of many predisposing factors is presently well recognized and we should be capable of defining interventions related to some of them as is the case of early institution of day-care, short duration of breast feeding and difficulties in the identification and treatment of gastroesophageal reflux. Changes in the microbiology of the middle ear infections and the emergence of multiresistant bacteria leads to modifications in antibiotic therapy and the duration of its use. Antibacterial agents should be prescribed only in the presence of a well-defined diagnosis and chemoprophylaxis should be avoided. Recurrent otitis media and otitis media with effusion in infants may be associated to speech disorders and learning disabilities. The development of a conjugated vaccine against S. pneumoniae and the experiments with a vaccine against non-typeable H. influenzae represent a big step in the prevention of infections of the middle ear for the near future.