Use of CAR-T cells for the treatment of relapsed and refractory multiple myeloma: a systematic review / Uso de células CAR-T no tratamento de mieloma múltiplo recidivado e refratário: uma revisão sistemática

A systematic review of published articles based on randomized clinical trials was conducted to ascertain the efficacy or perspective of using CAR-T cell therapy for refractory multiple myeloma. The PubMed database was searched with the combination of terms "multiple myeloma", "refractory multiple myeloma", "CAR T-cell", and the PRISMA criteria were followed. Of the 78 articles found, only 5 were selected. The studies used different treatment protocols and four different types of CAR-T cells. All studies obtained interesting results in terms of increased progression-free survival and negative minimal residual disease responses. Some authors detected an expansion of CAR-T cells and noted dose-dependent relationship between treatment effectiveness and serum BCMA levels. Although the results were promising, a small number of patients still relapsed a few months after CAR-T cell infusion. Therefore, this new line of therapy should be further investigated, as it significantly increases progression-free survival and improves quality of life.

Uma revisão sistemática de artigos publicados com base em ensaios clínicos randomizados foi realizada para verificar a eficácia ou perspectiva do uso da terapia com células CAR-T para mieloma múltiplo refratário. Foi pesquisada a base de dados PubMed com a combinação dos termos "multiple myeloma", "refratory multiple myeloma", "CAR T-cell" e foram seguidos os critérios PRISMA. Dos 78 artigos encontrados, apenas 5 foram selecionados. Os estudos utilizaram diferentes protocolos de tratamento e quatro tipos diferentes de células CAR-T. Todos os estudos obtiveram resultados interessantes em termos de aumento da sobrevida livre de progressão e respostas negativas à doença residual mínima. Alguns autores detectaram uma expansão das células CAR-T e observaram uma relação dose-dependente entre a eficácia do tratamento e os níveis séricos de BCMA. Embora os resultados tenham sido promissores, um pequeno número de pacientes ainda apresentou recaída alguns meses após a infusão de células CAR-T. Portanto, esta nova linha de terapia deve ser mais investigada, pois aumenta significativamente a sobrevida livre de progressão e melhora a qualidade de vida.

Cervical Intraepithelial Neoplasia grade 2 biopsy: Do p16INK4a and Ki-67 biomarkers contribute to the decision to treat? A cross-sectional study

ABSTRACT BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies.

Factores pronósticos de metástasis ósea en pacientes con cáncer de próstata / Predictive factors for bone metastasis in patients with prostate cancer i: en

El adenocarcinoma de próstata es considerado una de las neoplasias más frecuentes en hombres mayores de 60 años, y su metástasis ósea constituye una de las complicaciones de peor pronóstico. Objetivo: Estimar los factores pronósticos de metástasis ósea en pacientes con cáncer de próstata. Métodos: Se realizó un estudio analítico de 73 pacientes con cáncer de próstata, asistidos en el Hospital Oncológico Conrado Benítez de Santiago de Cuba en el período 2018-2022. Entre las variables analizadas figuraron: edad, color de la piel, manifestaciones clínicas, tiempo de aparición de la metástasis ósea, grado de diferenciación celular, nivel de antígeno prostático específico y diagnóstico imagenológico. Resultados: En la serie predominó el grupo etario de 60-69 años (50,7 %) y el promedio de edad fue de 67 años; asimismo, prevalecieron los pacientes de piel negra, el dolor óseo como síntoma más frecuente y el diagnóstico imagenológico de metástasis ósea por tomografía axial computarizada (48,0 %). Se observó un aumento proporcional de los valores del antígeno prostático específico y de la puntuación de Gleason en relación con la aparición de metástasis. Conclusiones: Los factores pronósticos que permiten estimar la presencia de metástasis ósea en pacientes con cáncer de próstata son la edad avanzada, el color negro de la piel y los valores de antígeno prostático específico por encima de 20 ng/mL.

Prostate adenocarcinoma is considered one of the most frequent neoplasms in men over 60 years, and bone metastasis constitutes one of the complications with the worst prognosis. Objective: Estimate the predictive factors for bone metastasis in patients with prostate cancer. Methods: An analytic study of 73 patients with prostate cancer was carried out. They were assisted at Conrado Benítez Cancer Hospital in Santiago de Cuba during 2018-2022. The variables analyzed included: age, skin color, clinical manifestations, onset time of bone metastasis, degree of cellular differentiation, prostate-specific antigen level and imaging diagnosis. Results: In the series there was a prevalence of the 60-69 age group (50.7%) and the average age was 67 years; also, dark skinned patients, bone pain as more frequent symptom and imaging diagnosis of bone metastasis by computerized axial tomography prevailed (48.0%). A proportional increase of prostate-specific antigen values and Gleason punctuation was observed in relation to the metastasis onset. Conclusions: The predictive factors for estimating the presence of bone metastasis in patients with prostate cancer are the advanced age, black skin color and prostate-specific antigen values above 20 ng/mL.

Estudio comparativo entre un test de antígeno y la prueba de la reacción en cadena de la polimerasa en tiempo real (RT-PCR) para el diagnóstico de infección por COVID-19 en pediatría / Comparative study between an antigen test and the reverse transcription-polymerase chain reaction (RT-PCR) test for the diagnosis of COVID-19 in pediatrics

Introducción. La pandemia por COVID-19 ha puesto de manifiesto la necesidad de pruebas diagnósticas rápidas. La prueba de referencia es la reacción en cadena de la polimerasa en tiempo real (RT-PCR). Requiere un equipo y personal capacitado, y su resultado puede llevar un tiempo de espera prolongado. El sistema BD Veritor® es el método rápido cromatográfico utilizado para la detección del antígeno del coronavirus de tipo 2 del síndrome respiratorio agudo grave, en individuos sintomáticos. El objetivo primario del siguiente trabajo es evaluar sensibilidad y especificidad del test de antígeno (TA) comparadas con la RT-PCR en población pediátrica. Población y métodos. Estudio prospectivo, de prueba diagnóstica. Se incluyó a todo menor de 17 años en los primeros 5 días de inicio de síntomas, que consultó desde julio de 2021 hasta febrero de 2022. Se calculó un mínimo de 300 muestras para lograr una precisión de ± 8,76 % y de ± 3,68 % para sensibilidad y especificidad respectivamente. Se analizaron en paralelo las muestras por ambas metodologías. Resultados. De 316 muestras pareadas, 33 fueron positivas por ambos métodos; 6 fueron positivas solo por RT-PCR. La especificidad del TA fue del 100 %; la sensibilidad, del 84,6 %, con un valor predictivo positivo y negativo del 100 % y del 98 % respectivamente. Conclusiones. El TA demostró ser útil en el diagnóstico de pacientes pediátricos con COVID-19 en los primeros 5 días de inicio de síntomas, aunque aquellos con TA negativo y alta sospecha clínica deberían confirmar su resultado con la RT-PCR.

Introduction. The COVID-19 pandemic has brought to light the need for rapid diagnostic tests. The gold standard test is reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR requires equipment and trained personnel, and results may take a long waiting time. The BD Veritor® System is a rapid chromatographic method used for the detection of severe acute respiratory syndrome coronavirus 2 antigen in symptomatic individuals. The primary objective of this study is to assess the sensitivity and specificity of the antigen test (AT) compared to the RT-PCR in the pediatric population. Population and methods. Prospective study with a diagnostic test. All children younger than 17 years in the first 5 days of symptom onset, who consulted between July 2021 and February 2022, were included. A minimum of 300 specimens was estimated to achieve an accuracy of ±8.76% and ±3.68% for sensitivity and specificity, respectively. Specimens were analyzed in parallel using both methodologies. Results. Of 316 paired samples, 33 were positive by both methods; 6 were positive only by RT-PCR. The specificity of the AT was 100%; sensitivity was 84.6%, with a positive and negative predictive value of 100% and 98%, respectively. Conclusions. The AT proved to be useful in the diagnosis of pediatric patients with COVID-19 in the first 5 days of symptom onset, although those with a negative AT and high clinical suspicion should confirm their result with a RT-PCR.

Revisiting ab initio carcinoembryonic antigen and CA19-9 tumor markers in colorectal carcinoma in association with anatomotopographic location and staging of disease

SUMMARY OBJECTIVE: This study purposed to evaluate preoperative two tumor markers, namely, carcinoembryonic antigen and carbohydrate antigen (CA)19-9, in colorectal cancer for anatomotopographic location with disease stage and to assess their utility for diagnostic staging purposes. METHODS: The study retrospectively incorporated patients who had undergone surgery for colorectal cancer at our department in 2015-2018 and in whom carcinoembryonic antigen and CA19-9 tumor markers had been preoperatively analyzed. The obtained data were then statistically processed using R-project. RESULTS: A total of 155 patients had been incorporated, of whom 96 (62%) were men and 59 (38%) were women. Rectum was the most common location (74 patients, 48%), and the least represented stage was IV (18, 12%). The marker carcinoembryonic antigen was obtained in all 155 cases, while CA19-9 was in 105. The median carcinoembryonic antigen was 3 (0.34-1104.25), and the median CA19-9 was 12 (0.18-840.00). A significance was recognized between median carcinoembryonic antigen and disease stage (p-value=0.016), with stages I, II, and III (medians 2, 3, and 2) different from stage IV (median 13), while no significance for CA19-9 was recognized (p-value=0.343). No significance between either marker and location (carcinoembryonic antigen: p=0.276; CA19-9: p=0.505) was detected. The testing was performed at a significance level of alpha=0.05. CONCLUSION: This study revealed a significance between the marker carcinoembryonic antigen, but not CA19-9, and the disease stage, while no relationship of either of these markers with tumor location was found. Herewith, the study confirmed that higher carcinoembryonic antigen values may suggest the finding of more advanced forms of colorectal cancer and thus a worse prognosis of this malignant phenomenon.

Evaluation of bowel wall flow by color Doppler ultrasound in the assessment of inflammatory bowel disease activity in pediatric patients / Avaliação do fluxo parietal pela ultrassonografia com Doppler em cores no diagnóstico de atividade na doença inflamatória intestinal em pacientes pediátricos

Abstract Objective: To assess inflammatory bowel disease (IBD) activity with Doppler ultrasound in pediatric patients, comparing the accuracy of the ultrasound findings with that of the concentrations of fecal calprotectin (FC). Materials and Methods: In a consecutive series, we evaluated 53 examinations of 44 pediatric patients seen between 2014 and 2020: 28 with Crohn's disease, 15 with ulcerative colitis, and one with IBD unclassified. The diagnosis of IBD was made in accordance with the Porto criteria. The alteration studied in the greatest detail was bowel wall flow, which was classified by the lead investigator and two pediatric radiologists, all of whom were blinded to the FC concentrations and the other ultrasound findings. Bowel wall flow was categorized as low if there were up to 2 Doppler ultrasound signals/cm2, moderate if there were 3-5 signals/cm2, and high if there were more than 5 signals/cm2. Results: The agreement among the radiologists was substantial (kappa = 0.73). In cases in which ultrasound showed low bowel wall flow, the median FC concentration was 92 µg/g (interquartile range, 33-661 µg/g), whereas it was 2,286 µg/g (interquartile range, 1,728-5,612 µg/g) in those in which ultrasound showed high bowel wall flow. In the sample as a whole, the sensitivity and specificity of ultrasound was 89.7% and 92.0%, respectively, for the detection of inflammatory activity; 95.5% and 90.9%, respectively, for the detection of Crohn's disease; and 81.3% and 100.0%, respectively, for the detection of ulcerative colitis. Conclusion: Ultrasound of the bowel wall showed a strong correlation with FC concentrations in the assessment of inflammatory activity in pediatric patients with IBD.

Resumo Objetivo: Avaliar a atividade da doença inflamatória intestinal (DII) por ultrassonografia (US) com Doppler em cores, comparada à concentração de calprotectina fecal (CF) em pacientes pediátricos. Materiais e Métodos: Em uma série consecutiva, no período entre 2014 e 2020, foram avaliados 53 exames de 44 pacientes pediátricos: 28 casos de doença de Crohn, 15 de colite ulcerativa e um de colite indeterminada. O diagnóstico da DII foi feito pelos critérios de Porto. O fluxo parietal foi a alteração estudada mais detalhadamente e classificada pelo pesquisador principal e por dois radiologistas pediátricos cegados aos valores de CF e de US Doppler. Baixo fluxo parietal foi definido pela captação de até 2 sinais de US Doppler/cm2, fluxo moderado entre 3 e 5 sinais/cm2 e alto fluxo mais de 5 sinais/cm2. Resultados: Houve concordância substancial entre os radiologistas (kappa = 0,73). Nos exames com baixo fluxo parietal a CF média foi 92 μg/g (intervalo interquartil: 33-661 μg/g) e nos exames com alto fluxo a CF média foi 2.286 μg/g (intervalo interquartil: 1.728-5.612 μg/g). Na amostra total, a US demonstrou sensibilidade de 89,7% e especificidade de 92,0% para detecção da atividade inflamatória, 95,5% e 90,9% na doença de Crohn e 81,3% e 100,0% na colite ulcerativa, respectivamente. Conclusão: Houve forte correlação entre a US da parede intestinal e os valores da concentração de CF na avaliação da atividade inflamatória na DII de pacientes pediátricos.

Rol actual del antígeno carcinoembrionario (CEA) en el manejo del cáncer de colon

El antígeno carcinoembrionario (CEA) es un marcador tumoral ampliamente empleado en el manejo del cáncer colorrectal, especialmente en el seguimiento de los pacientes resecados con intención curativa. El objetivo de esta revisión es actualizar el rol del CEA en el manejo de los pacientes intervenidos por un cáncer de colon estadios I-III considerando la mejor evidencia disponible. Dada la sensibilidad modesta en el tumor primario (40%), la cual sube al 60-80% en los casos de recidiva, se propone la medición precoz del marcador (alrededor del mes) de las resecciones R0, toda vez que el valor debiera estar normalizado, especialmente si estaba elevado en el preoperatorio. Una elevación sostenida o un alza > de 10 ng/ml en el control precoz es indicativo de enfermedad residual y/o a distancia, lo que implica un rastreo clínico intensivo. Aunque el CEA preoperatorio tiene un valor pronóstico categórico, el CEA postoperatorio precoz elevado parece tener un valor pronóstico de recidiva superior. Un seguimiento intensivo parece razonable en los pacientes con factores de riesgo de recidiva, lo que incluye la medición del CEA en forma seriada. El umbral óptimo del CEA es motivo de controversia, con una tendencia a bajar el nivel de corte considerado normal (< 5 ng/ml) en los últimos años), lo que podría mejorar el balance entre sensibilidad y especificidad del test. Nuevas técnicas como el ADN circulante en combinación con el CEA se han propuesto para mejorar la oportunidad del diagnóstico de una recidiva, actualmente en evaluación.

Carcinoembryonic antigen (CEA) is a tumor marker widely used in the management of colorectal cancer, especially in the follow-up of patients resected with curative intent. The objective of this review is to update the role of CEA in the management of patients operated on for stage I-III colon cancer considering the best available evidence. Given the modest sensitivity in the primary tumor (40%), which rises to 60-80% in cases of recurrence, early measurement of the marker (around a month) of R0 resections is proposed, since the value should be normalized, especially if it was elevated preoperatively. A sustained elevation or a rise > 10 ng/mL at early check-up is indicative of residual and/or distant disease, which implies intensive clinical follow-up. Although preoperative CEA has a strong prognostic value, elevated early postoperative CEA seems to have a higher prognostic value for recurrence. Intensive follow-up seems reasonable in patients with risk factors for recurrence, which includes serial CEA measurement. The optimal CEA threshold is controversial, with a tendency to lower the cut-off level considered normal (< 5 ng/ml) in recent years), which could improve the balance between test sensitivity and specificity. New techniques such as circulating DNA in combination with CEA have been proposed to improve the chance of diagnosing a recurrence, currently under evaluation.

Frequency of the DI*A, DI*B and Band 3 Memphis polymorphism among distinct groups in Brazil

ABSTRACT Introduction: The Band 3 is a red blood cell protein that carries the Dia and Dib antigens from the Diego blood system. The SLC4A1 gene encodes Band 3; Band 3 Memphis is a polymorphism of normal Band 3 and has two variants, but only the variant II carries the Dia antigen. Objectives: Describe the frequencies of the DI*A and DI*B alleles and the Band 3 Memphis among blood donors, sickle cell disease (SCD) patients and Amazonian Indians. Methods: A total of 427 blood samples were collected and separated into three groups: 206 unrelated blood donors, 90 patients with SCD and 131 Amazonian Indians. We performed DI*A/B, normal Band 3 and Band 3 Memphis genotyping, using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP). Results: The frequency of the DI*A/DI*A genotype was 0.5% in blood donors and it was not found in other groups. The frequency of the DI*A/DI*B was higher in Amazonian Indians (33.6%) and the frequency of the DI*B/DI*B was highest in blood donors (92.2%). All 105 individuals tested were positive for the presence of normal Band 3 and of these individuals, only 5/105 (4.8%) presented the Band 3 Memphis mutation. Conclusion: We observed a higher frequency of the DI*B allele in blood donors and a low frequency of the DI*A/DI*A genotype in all groups studied. The Band 3 Memphis was found in a higher frequency in the blood donor group. Our findings highlight the importance of analyzing different population groups to gain a better understanding of the genetic association of blood group antigens.

Intravascular papillary endothelial hyperplasia: Olanzapine-induced vascular proliferation?

Intravascular papillary endothelial hyperplasia (Masson's tumor) is a reactive vascular lesion of obscure etiopathogenesis, often seen in the head and neck. Its presentation as a scalp swelling, however, is extremely uncommon. We describe the first report in an adult, being treated for bipolar illness. A young male presented with a right frontotemporal scalp swelling since 3 weeks. He was also being treated for bipolar illness with olanzapine. Examination revealed a soft, non-pulsatile swelling. After inconclusive aspiration results, a complete excision was performed. Histopathology revealed proliferating endothelial cells arranged as papillary fronds confined to vessel lumina, devoid of atypia, accompanied by thrombosed vessels facilitating a diagnosis of Masson's tumor. The patient is free of recurrence five months after surgery. Further studies on a possible effect of olanzapine on vascular proliferation in experimental in vivo and in vitro models would definitely aid in elucidating clinical relevance, if any.

New cost-effective human leukocyte antigen testing algorithm for screening of human leukocyte antigen-matched related donor in thalassemia major patient pretransplant workup: A single-center study from resource-constrained settings

Introduction: India has a huge disease burden of thalassemia major with an estimated 40 million carriers and over a million thalassemia major patients. Very few patients are optimally treated, and the standard of care “hematopoietic stem cell transplant” (HSCT) is out of reach for most patients and their families. The cost of HSCT is significant, and a substantial proportion of it goes to human leukocyte antigen (HLA) testing of family members (HLA screening) in hope of getting a matched related donor (MRD) for HSCT. The aim of this study was to establish that a new proposed testing algorithm of HLA typing would be more cost-effective as compared to the conventional HLA screening within MRD families for possible HSCT. Material and Methods: Buccal swab samples of 177 thalassemia patients and their prospective family donors (232) were collected. Using a new HLA testing algorithm, samples were tested for HLA typing in a sequential manner (first HLA-B, then HLA-A, and finally HLA-DR) using the sequence-specific oligonucleotide probe method on the Luminex platform. Results: The new sequential HLA-A, HLA-B, and HLA-DRB1 testing algorithm showed a 49.1% reduction in cost compared to the conventional HLA testing algorithm. Furthermore, 40 patients (22.59%) were found to have HLA-MRD within the family among other samples that were tested. Conclusion: The new HLA testing algorithm proposed in the present study for identifying MRD for HSCT resulted in a substantial reduction in the cost of HSCT workup.

Clinicopathological correlation of various prostatic lesions with serum prostate-specific antigen level – A hospital-based cross-sectional study

Background: The prostate is a male reproductive accessory gland which gives rise to several pathological conditions. The present study aims to study the correlation of histopathology of prostatic diseases with the clinical profile of the patient coming to VSS Medical College (VSSMC), Burla for histopathological reporting of prostatic biopsies. Aim and Objectives: The objectives of this study were as follows: (1) To correlate serum prostate-specific antigen (PSA) level with various clinical and pathological lesions of the prostrate gland, in a Hospital-based sample of Western Odisha population. (2) As the male gender represents almost half of the entire population, to find out different clinicopathological lesions, percentage-wise, so as to know the frequency of occurrence of such lesions. Materials and Methods: Fifty-seven cases of prostatic diseases were recorded in the Department of Pathology, VSSMC, Burla for histopathological examination of prostatic tissue for 2 years from September 2017 to August 2019. All the samples were fixed in 5 ? sections with 10% neutral buffered formalin. Then Hematoxylin and Eosin stain (H and E stain) was used for staining. Appropriate clinical data comprising signs and symptoms, laboratory findings, and serum PSA levels were recorded. Results: The present study, in the beginning, consisted of 64 patients, out of which seven patients were excluded by exclusion criteria, and finally, 57 cases were analyzed. The most prevalent age group for all prostatic diseases was 61–70 years with a mean of 67 years. The majority of the cases (73.67%) were benign mostly benign prostatic hyperplasia (BPH). Prostatic intraepithelial neoplasia (PIN) was 12.29% and malignant cases (all adenocarcinoma) were also 12.29%. All patients showed prostatomegaly. About 50% of cases suggestive of malignancy by digital rectal examination (DRE) were confirmed to be carcinoma by histopathological study. Serum creatinine level was raised in 16.27% of benign and 21.42% of premalignant and malignant conditions. Serum PSA level below 4 ng/mL were all benign and above 10 ng/mL were majority malignant conditions. However, at level 4–10 ng/mL, BPH and PIN cases were overlapped with cases of carcinoma. Conclusion: Benign prostatic hyperplasia is the most commonly encountered prostatic lesion. Serum PSA level <4 ng/mL is associated with benign conditions and more than 10 ng/mL is associated more with carcinomas. Although, investigations such as DRE and serum PSA estimation aid in diagnosis, a definitive diagnosis of benign and malignant lesions of prostate can be made by histopathological study of prostatic biopsies.

Inmunolocalización de citoqueratina 14, 19 y Ki-67 en el epitelio de pacientes con agrandamiento gingival

R E S U M E N En pacientes con ortodoncia aparecen eventos patológicos no deseados como agrandamiento gingival inducido por tratamiento de ortodoncia (AGTO) o hipertrofia gingival. El objetivo del estudio es identificar la distribución inmunohistoquímica de citoqueratina CK-14, CK-19 y Ki-67 en epitelio gingival de pacientes con AGTO. Se seleccionaron I3 pacientes divididos en: grupo control (n=6), conformado por individuos periodontalmente sanos no portadores de aparatología ortodóntica y grupo test (n=7), integrado por pacientes con AGTO. Los marcadores CK-14, CK-19 y Ki-67 fueron identificados mediante inmunohistoquímica con anticuerpos monoclonales y observados en un microscopio óptico Leica DM 500. En los pacientes del grupo test el tejido epitelial se mostró hipertrófico con pérdida en la continuidad de la membrana basal. La CK-14 y CK-19 fue positiva en el epitelio de todos los sujetos evaluados, con una expresión positiva de alta intensidad en células de la lámina basal del grupo test. El promedio de células positivas para Ki-67 en el grupo test fue de 56%. En conclusión, la CK-14, CK-19 y Ki-67 son marcadores con elevada inmunoreactividad en tejido gingival de pacientes con AGTO portadores de ortodoncia.

During orthodontic treatment, unwanted pathological events such as gingival overgrowth induced by orthodontic treatment or gingival hypertrophy may appear The objective of this study is to identify immunohistochemical distribution of cytokeratin CK-14, CK-19 and Ki-67 in the gingival epithelium of patients with gingival overgrowth induced by orthodontic treatment. Thirteen patients were selected divided into: control group (n = 6), conformed of periodontally healthy individuals without orthodontic appliances and the test group (n = 7), conformed of patients with gingival overgrowth induced by orthodontic treatment. The biomarkers CK-14, CK-19 and Ki-67 were identified by immunohistochemistry with monoclonal antibodies and observed in a Leica DM 500 optical microscope. Hypertrophic epithelial tissue with loss of continuity of the basement membrane was found in the test group patients. CK-14 and CK-19 were positive in the epithelial tissue of all the subjects evaluated, with a high intensity positive expression in the cells of the basal lamina of the test group. The average number of cells positive for Ki-67 in test group was 56%. In conclusion, CK-14, CK-19 and Ki-67 are biomarkers with high immunoreactivity in the gingival tissue of patients with gingival overgrowth induced by orthodontic treatment.

Durante o tratamento ortodôntico, eventos patológicos indesejados como o crescimento gengival induzido pelo tratamento ortodôntico (CGTO) ou hipertrofia gengival podem aparecer: O objetivo deste estudo é identificar a distribuição imuno-histoquímica das citoqueratinas CK -14, CK-19 e Ki-67 no epitélio gengival de pacientes com CGTO. Foram selecionados 13 pacientes divididos em: grupo controle (n=6), conformado por indivíduos periodontalmente saudáveis sem aparelhos ortodônticos e o grupo teste (n=7), conformado por pacientes com CGTO. Os biomarcadores CK-14, CK-19 e Ki-67 foram identificados por imuno-histoquímica com anticorpos monoclonais e observados em microscópio óptico Leica DM 500. Tecido epitelial hipertrófico com perda de continuidade da membrana basal foi encontrado nos pacientes do grupo teste. CK-14 e CK-19 foram positivos no tecido epitelial de todos os sujeitos avaliados, com expressão positiva de alta intensidade nas células da lâmina basal do grupo teste. O número médio de células positivas para Ki-67 no grupo teste foi de 56%. Em conclusão, CK-14, CK-19 e Ki-67 são biomarcadores com alta imunorreatividade no tecido gengival de pacientes com CGTO.

The Relationship Between Carcinoembryonic Antigen and Epicardial Adipose Tissue

Abstract Background: Inflammation, which is associated with an unhealthy lifestyle, plays a critical role in the development of both cardiometabolic diseases (CMD) and cancer. Carcinoembryonic antigen (CEA) is a tumor marker which also has proinflammatory properties. Recent studies have reported CEA to be associated with atherosclerosis, metabolic syndrome, and visceral adiposity. Epicardial adipose tissue (EAT) can exhibit highly inflammatory and pathogenic properties, and is a known risk factor for CMD. However, its relationship with CEA is still unknown. Objectives: This study aimed to investigate the possible association of CEA with EAT. Methods: A total of 134 Caucasian (males = 56, females = 78) individuals, aged (22-83 years), who were admitted for routine health control, were enrolled in this cross-sectional study. CEA was measured with chemiluminescent microparticle immunoassay (CMIA). EAT was measured by transthoracic echocardiography, and the visceral fat rating (VFR) was assessed by a body composition analyzing machine. The p-value <0.05 was considered statistically significant. Results: CEA levels were categorized as tertiles: T1, 0.5-1.04; T2, 1.06-1.69; and T3, ≥1.7 ng/ml. The mean age, weight, VFR, EAT, and fasting glucose, as well as the median of systolic blood pressure (SBP), creatinine, and AST increased with the increasing CEA tertiles. CEA was significantly associated with EAT (r = 0.55, P<0.001) and VFR (r = 0.36, P<0.001). Multivariate linear regression analysis confirmed that gender, age, and EAT were the significant independent variables associated with CEA. Conclusion: Individuals with increased EAT have higher levels of CEA, suggesting that this biomarker is most likely produced by EAT; however, additional investigations are required to improve the present work.

Use of Schirmer strips and conjunctival swabs for virus detection on the ocular surface of adults: a scoping review / Fitas de Schirmer e swab conjunctival para detecção de vírus na superfície ocular de adultos: scoping review

ABSTRACT Schirmer strips and conjunctival swabs are used in ophthalmology for the collection of tears and fluids. One of the biggest challenges during the COVID-19 pandemic has been accurate diagnosis and, in some cases, ocular manifestations are among the first symptoms. In this context, this study aimed to collect evidence to support the use of Schirmer strips and conjunctival swabs as a method of sample collection for viral analysis. A literature search was conducted following the Scoping Review protocol defined by The Joanna Briggs Institute. Studies were analyzed regarding virus research, collection methods, and sample analysis. The findings support that viruses can be detected on the ocular surface through analysis of Schirmer strips and conjunctival swabs. However, additional studies with larger samples and time data are necessary to confirm these conclusions.

RESUMO A fita de Schirmer e o swab conjunctival são utilizados na oftalmologia como métodos de coleta para lágrimas e fluidos. Durante a pandemia da COVID-19, um dos desafios foi o diagnóstico correto e se sabe que, em alguns casos, as manifestações oculares podem ser um dos primeiros sintomas. Nesse contexto, este estudo tem como objetivo levantar evidência que destaque o uso de fitas de Schirmer e de swabs conjuntivais como método de coleta para análise viral. Conduziu-se uma revisão de literatura seguindo o protocolo para Scoping Review definido pelo Joanna Briggs Institute. Os pesquisadores analisaram os estudos em busca do vírus pesquisado, os métodos de coleta e os métodos de análise. Vírus podem ser detectados na superfície ocular através da análise de fitas de Schirmer e de swabs conjuntivais, entretanto novos estudos com populações maiores e com definições claras de tempo são necessários para conclusões mais assertivas no tema.

Evaluation of cell adhesion molecules (LFA-1 and L-selectin) in ankylosing spondylitis patients after treatment with ?-D-mannuronic acid (M2000)

Background & objectives: To examine ?-D-mannuronic acid (M2000) effects on L-selectin shedding and leucocyte function-associated antigen-1 (LFA-1) expression as mechanisms of action of this drug in patients with ankylosing spondylitis (AS). Methods: To investigate the molecular consequences of ?-D-mannuronic acid on L-selectin shedding, flow cytometry method was used. Furthermore, the effect of it on LFA-1 gene expression was analyzed by using quantitative real time (qRT)-PCR technique. Results: The LFA-1 expression in patients with AS was higher than controls (P=0.046). The LFA-1 expression after 12 wk therapy with ?-D-mannuronic acid was meaningfully decreased (P=0.01). After 12 wk treatment with ?-D-mannuronic acid, the frequency of CD62L-expressing CD4+ T cells in patients with AS, was not considerably altered, compared to the patients before therapy (P=0.5). Furthermore, after 12 wk therapy with ?-D-mannuronic acid, L-selectin expression levels on CD4+ T-cells in patients with AS, were not remarkably changed, compared to the expression levels of these in patients before treatment (P=0.2). Interpretation & conclusions: The results of this study for the first time showed that ?-D-mannuronic acid can affect events of adhesion cascade in patients with AS. Moreover, ?-D-mannuronic acid presented as an acceptable benefit to AS patients and could aid in the process of disease management

Evaluation of prostate-specific antigen and total serum acid phosphatase in prostatic carcinoma

Background: The importance of prostatic carcinoma and its detection has increased manifold over the last few decades. Total serum acid phosphatase (ACP) was the world’s first emerged clinically useful tumor marker in the 1940s and 1950s in patients with prostatic diseases. With the introduction of the prostatic specific antigen (PSA) test in the 1980s, which performed significantly better in screening and treatment programs bringing disfavor to the advent of ACP. Aims and Objectives: To determine serum PSA and total serum ACP in patients with prostatic cancer and benign prostatic diseases, followed by evaluation of these tumor markers. Materials and Methods: This study was conducted on 30 patients with histologically proven cases of prostatic carcinoma and compared against 30 patients as control with benign prostatic pathology, residing in Punjab who were admitted and treated with symptoms complex of prostatism or retention urine or other urinary complaints as the primary symptoms. PSA and ACP in serum were determined using ELISA test kit and King and Kind method, respectively. Results: The mean level of serum PSA was 81.19 ± 49.02 for cancer prostate and 4.975 for benign prostatic diseases, while the mean level of serum ACP was 5.22 ± 1.70 and 2.52 ± 2.27, respectively, for the cancer prostate and benign prostatic diseases showing statistically difference between study and control groups was highly significant as P < 0.0001. Conclusion: Statistical analysis and results of the present study indicated that although serum ACP has better specificity to PSA, yet later is a very sensitive tumor marker in prostate diseases for screening, diagnosis, and post-treatment follow-up.

Agrandamiento gingival asociado al tratamiento de ortodoncia: análisis histológico e inmunohistoquímico de dos casos clínicos

El agrandamiento gingival asociado al tratamiento de ortodoncia (AGTO) es el crecimiento no controlado de la encía. Aquí reportamos dos casos clínicos de pacientes masculinos sistèmicamente sanos con AGTO generalizado, con asociación a la biopelícula dental y sin esta. En ambos pacientes se identificó un tejido epitelial hiperplásico con abundantes células positivas para Ki-67 y tejido conectivo rico en fibras de colágeno distribuidas aleatoriamente. Futuros estudios serán útiles para dilucidar las diferencias fisiopatológicas del AGTO con relación con el biofilm dental y sin esta.

Orthodontic treatment-induce gingival overgrowth (OTGO) is uncontrolled growth of the gingiva. Here, we report two clinical cases of systemically healthy male patients with generalized GH undergoing orthodontic treatment, with and without association with dental biofilm. In both patients, hyperplastic epithelial tissue was identified with abundant Ki-67 positive cells and connective tissue rich in randomly distributed collagen fibers. Future studies will be useful to elucidate the pathophysiological differences of OTGO with and without relation to dental biofilm.

Detection of Schistosma heamatobiumamong Orphanage Children Attending Jarma UK Orphanage Home and Bakin Gulbi Primary School Sokoto

Urinary schistosomiasis or Bilharzia caused by fluke worm Schistosoma haematobium(S. haematobium) is one of the seventeen (17) neglected tropical diseases associated with serious health problems and morbidities. It affects over 200 million people globally with an estimated death rate of more than 200, 000 annually and very common in Sub-Saharan African countries. The aim of the study was to determine the prevalence and associated risk factors of S. haematobiumand provide epidemiological data in part of Nigeria. This cross-sectional study was carried out on 202 consenting participants, using both maleand female attending Jarma Uk Orphanage home and Bakin Gulbi primary school. Detection and evaluation were done using Gold Standard Microscopy and commercially available Rapid Detection Test strips. Statistical analysis was carried out using a statisticalpackage (SPSS version 26). A prevalence of 34(16.8%) among 202 from gold standard microscopy and 13(6.4%) circulating cathodic antigen (CCA) were obtained. High infection risk was observed among participant on swimming as a recreational activity 32(15.8%)at p<0.046 A gender prevalence of 26 (12.87%) and 8 (3.96%) at p<0.067 from male and female respectively were obtained. Female at the age group 11-15 had 27 (13.36%), and those with agriculture as recreational activity had the least infection risk 2(0.99%). This study showed that CCA has a less sensitivity and specificity than gold standard microscopy.

The relationship between uric acid levels and graft function in renal transplant patients who discontinued steroid therapy / Relación entre niveles de ácido úrico y función del injerto en pacientes de trasplante renal que interrumpieron la terapia con esteroides

ABSTRACT Introduction: High uric acid levels are commonly encountered in kidney transplant recipients, and can be associated with allograft dysfunction. Our study aims to examine the relationship between UA levels and graft function in patients discontinuing steroids. Methods: In this single-center-retrospective study, 56 patients discontinued steroid therapy from among 678 RT patients transplanted from living donors between 1999-2020 were included. The mean age of the study group was 45.8±8.8 years. Causes of steroid discontinuation, creatinine levels concurrent with uric acid levels before and after steroid discontinuation (mean 3.9 ± 2.1 years), acute rejection numbers, demographics, durations of dialysis and transplantation, medications, laboratory data, human leukocyte antigen (HLA) mismatch numbers, blood-pressure (BP), body mass index, delayed acute rejection (DAR) numbers (3 months post-transplantation) were all recorded. Results: Creatinine and uric acid levels were seen to have increased after steroid discontinuation, there was a significant relationship between them (p<0.001). Statistically significant correlation was found between increased creatinine levels after steroid discontinuation and graft survival with higher HLA mismatch; 39 (69.6%) patients with mismatch ≥2, and 17 patients with mismatch <2 (30.4%) (p=0.049) . No significant relationship was found between DAR numbers before and after steroid discontinuation, and creatinine levels after steroid discontinuation. Conclusion: Per model obtained as a result of multivariate linear analysis, hyperuricemia and HLA mismatch numbers (p= 0.048 and p= 0.044, respectively) are independent predictive factors for graft dysfunction in patients discontinuing steroids. Accordingly, negative effects of modeling should be kept in mind for long-term graft survival in patients who plan to continue with steroid-sparing regimens.

RESUMEN Introducción: Con frecuencia se registran niveles elevados de ácido úrico en receptores de trasplantes renales que pueden estar asociados a disfunción de aloinjerto. El presente estudio tiene por objeto examinar la relación entre los niveles de AU y la función del injerto en pacientes que interrumpieron la terapia con esteroides. Métodos: En este estudio retrospectivo en un solo centro participaron 56 pacientes con interrupción de la terapia con esteroides de un total de 678 pacientes con TR receptores de trasplante de donantes vivos en el período 1999-2020. La edad promedio de la población de estudio fue de 45,8 ± 8,8 años. En el estudio se registraron causas de la interrupción de la terapia con esteroides, niveles de creatinina concurrentes con niveles de ácido úrico antes y después de la interrupción de la terapia con esteroides (promedio de 3,9 ± 2,1 años), números de rechazo agudo, datos demográficos, duraciones del período de diálisis y trasplante, medicación (uso de inmunosupresores, antihipertensivos), datos de laboratorio, números de desajuste del antígeno leucocitario humano (HLA), presión arterial (PA), índice de masa corporal, números de rechazo agudo retardado (DAR) (3 meses después del trasplante). Resultados: Se observó que los niveles de creatinina y ácido úrico aumentaron tras interrumpir la administración de esteroides, con una relación significativa entre ambos (p<0,001). Se identificó una correlación estadísticamente significativa entre el aumento en los niveles de creatinina tras la interrupción de la terapia de esteroides y la supervivencia del injerto con un mayor desajuste de HLA: 39 pacientes (el 69,6%) con desajuste ≥2 y 17 (el 30,4%) pacientes con desajuste <2 (p=0,049). No se encontró una relación significativa entre el número de DAR antes y después de la interrupción del tratamiento con esteroides, así como en los niveles de creatinina tras la interrupción de la terapia con esteroides. Conclusión: De acuerdo con el modelo obtenido como resultado del análisis lineal multivariable, la hiperuricemia y los números de desajuste de HLA (p=0,048 y p=0,044, respectivamente) constituyen factores predictivos independientes para la disfunción del injerto en pacientes que interrumpen la terapia con esteroides. En consecuencia, se deben tener en cuenta los efectos negativos del modelado para la supervivencia del injerto a largo plazo en pacientes que planean proseguir con regímenes con reducción de la administración esteroides.

SARS-CoV-2 antigen detection in deceased bodies: implications for infection prevention

Background & objectives: High transmissibility of the SARS-CoV-2 has significant implications on healthcare workers’ safety, preservation, handling, transportation and disposal of the deceased bodies. The objective of this study was to detect SARS-CoV-2 antigen in nasopharyngeal samples and its implications in handling and care of COVID-19 deceased bodies. Methods: A study was conducted at a dedicated COVID-19 centre on deceased individuals from April to December 2020. Rapid antigen test (RAT) and reverse transcription (RT)-PCR was compared on all the SARS-CoV-2 positive cadavers recruited in the study. Results: A total of 115 deceased individuals were included in the study. Of these, 79 (68.7%) were male and 36 (31.3%) were female and majority were in the age group of 51-60 yr [31 (27%)]. SARS-CoV-2 antigen test was positive in 32 (27.8%) and negative in 83 (72.1%) individuals. The mean time interval between deaths to the sample collection was 13.2 h with interquartile range of eight to 20 h. Reverse transcription (RT)-PCR was used as the reference test and 24 (20.9%) cases were true positive; 93.6 per cent [95% confidence interval (CI) 88.8-98.4%] sensitivity, 45.2 per cent (95% CI 35.5-55%) specificity, 60.2 per cent (95% CI 50.6-69.8%) positive predictive value and 88.8 per cent (95% CI 82.7-95%) negative predictive value of antigen test was computed. Interpretation & conclusions: SARS-CoV-2 antigen test was positive beyond 19 h in COVID-19 deceased individuals. Antigen test was found to be highly sensitive in the deceased. Patients, suspected of having died due to COVID-19, can be screened by this method. As infectiousness of the virus in the deceased bodies cannot be directly concluded from either the antigen or RT-PCR test, yet possible transmission cannot be completely ruled out. Strict infection control measures need to be followed during the handling and clearance of COVID-19 cadavers.