Linfoma de células B primario de mama en una paciente con sida. Presentación de un caso y revisión de la literatura / Primary B-cell lymphoma of the breast in an AIDS patient. Case report and literature review

Los LNH constituyen la segunda neoplasia más frecuente en pacientes con VIH. Estas neoplasias están ligadas a la inmunodeficiencia, suelen ser de período de latencia prolongado y más frecuentes en hombres. Más del 95% de estas neoplasias son de fenotipo B, de alto grado de malignidad, extranodales y representan la causa de muerte en un 12% al 16% de los casos. El linfoma no Hodgkin primitivo de mama (LPM) es una entidad infrecuente, que representa el 2,2% de todos los linfomas extranodales y el 0,5% de todas las neoplasias malignas de la mama. Se presenta una mujer con sida y linfoma primario de mama. (AU)

NHL is the second most common neoplasm in patients with HIV. It is linked to immunodeficiency, tends to have a long latency period and is more common in men. More than 95% of these neoplasms are of phenotype B, high-grade, extranodal and are the cause of death in 12% to 16% of cases. Primitive non-Hodgkin lymphoma of the breast is a rare entity, accounting for 2.2% of all extranodal lymphomas and 0.5% of all breast malignancies. A woman with AIDS and primary breast lymphoma is presented. (AU)

Una inusual causa de estrechez de la vía aérea laringotraqueal / An unusual cause of laryngotracheal airway narrowing

La enfermedad relacionada con inmunoglobulina (Ig) G4 es una enfermedad de reciente conocimiento que puede comprometer cualquier órgano teniendo preferencias por ciertas regiones del cuerpo, donde la región de cabeza y cuello es uno de sus principales puntos afectados, pudiendo comprometer tanto la órbita, glándulas salivales, glándulas lagrimales, glándula tiroides, cavidades paranasales, hueso temporal, faringe y laringe. Este último órgano es infrecuentemente comprometido, solo existiendo 12 casos registrados en la literatura antes de la publicación de este escrito. Presentamos un caso de una mujer de 49 años con historia de disnea frente a esfuerzo, diagnosticándose una estenosis subglótica la cual fue manejada quirúrgicamente con una reconstrucción laringotraqueal. En el estudio histopatológico se evidenció histología compatible con enfermedad relacionada con IgG4, por lo que se inició tratamiento médico con corticotera- pia oral por un lapso de 2 meses en conjunto con inmunología. Paciente luego de 4 años de seguimiento, no ha presentado recaídas, manteniendo un lumen subglótico adecuado.

Immunoglobulin (Ig) G4-related disease is a medical condition of recent knowledge that can compromise any organ, having preferences for certain regions of the body, where the head and neck region is one of the main affected points, being able to affect orbit, salivary glands, lacrimal glands, thyroid gland, paranasal cavities, temporal bone, pharynx and larynx. The latter is infrequently compromised, with only 12 cases registered in the literature before the publication of this writing. We present a case of a 49-year-old woman with a history of exertional dyspnea, diagnosed with a sub- glottic stenosis which was managed surgically with laryngotracheal reconstruction. The histopathological study revealed histology compatible with IgG4-related disease, so medical treatment with oral corticosteroid therapy was started for a period of 2 months in conjunction with immunology. After 4 years of follow-up, the patient has not presented relapses, maintaining an adequate subglottic lumen.

Hemostasia en cirugía funcional endoscópica (CEF): Revisión de las recomendaciones de la literatura internacional / Hemostasis in functional endoscopic sinus surgeries (FESS): Review of the international literature recommendations

El manejo del sangrado en CEF es fundamental, ya que aumenta la tasa de complicaciones. El principal objetivo del manejo perioperatorio es lograr una buena hemostasia, es por esto que se realizó una revisión de las principales recomendaciones de la literatura internacional, que incluye medidas preoperatorias, intraoperatorias y postoperatorias.

Bleeding is an important factor in FESS since it increases the rate of complications. The main objective of perioperative management is to achieve good hemostasis. This is a review of the main recommendations of the international literature, that includes preoperative, intraoperative and postoperative measures.

Expression of IGLL1 Gene and Its Clinical Significance in Pediatric T-ALL / 中国实验血液学杂志

OBJECTIVE@#To detect the relative expression of IGLL1 (immunoglobulin lambda-like polypeptide 1) mRNA in bone marrow of children with T-cell acute lymphoblastic leukemia (T-ALL), and analyze its correlation with the clinical characteristics and prognosis of the patients, so as to clarify the clinical significance of IGLL1 in pediatric T-ALL patients.@*METHODS@#A total of 56 pediatric T-ALL patients hospitalized in Children's Hospital of Soochow University from June 2012 to December 2017 and treated with CCLG-ALL 2008 regimen were selected. Transcriptome sequencing technology was used to detect the transcription level of IGLL1 gene in children with T-ALL. According to 25% of the IGLL1 transcription level (cutoff value:448), the enrolled children were divided into IGLL1 low expression group (17 cases) and IGLL1 high expression group (39 cases). Combined with clinical data, the correlation between the expression level of IGLL1 and prognosis of the patients was analyzed.@*RESULTS@#The comparative analysis showed that the transcription level of IGLL1 was not correlated with the clinical characteristics of the patients, such as sex, age, bone marrow blast, white blood cell (WBC) count at initial diagnosis. The 5-year OS rate of patients with high IGLL1 expression was significantly higher than that of patients with low IGLL1 expression (76.9%±6.7% vs 47.1%±12.1%, P =0.018). Further comparison of relapse-free survival (RFS) rate between the two groups showed that the 5-year RFS rate of patients with high IGLL1 expression was higher than that of patients with low IGLL1 expression, but the difference between the two groups was not statistically significant (P =0.095). Multivariate COX analysis was conducted on common clinical prognostic factors (age, sex, WBC count at diagnosis, prednisone response on the 7th day, bone marrow response on the 15th day after treatment) and IGLL1 expression level, and the results showed that IGLL1 expression (P =0.012) and prednisone response (P =0.017) were independent risk factors for overall survival in pediatric T-ALL patients.@*CONCLUSION@#In pediatric T-ALL, the OS rate of children with high expression of IGLL1 gene was significantly higher than that of children with low expression of IGLL1 gene, and the expression level of IGLL1 gene was an independent factor affecting the survival of children with T-ALL, which suggests that IGLL1 is a marker of good clinical prognosis of children with T-ALL.

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution / 中华医学杂志(英文版)

BACKGROUND@#To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution.@*METHODS@#This retrospective study included 115 newly diagnosed patients with WR-DLBCL, of whom 68 patients received R-CHOP, and 47 patients received DA-EPOCH-R as their first-line treatment. The baseline features of the two groups were well balanced using a 1:1 propensity score matching method, and a total of 84 cases were obtained, including respective 42 cases in the R-CHOP and DA-EPOCH-R groups, for further survival and prognosis analysis. The primary objectives included progression-free survival (PFS) and overall survival (OS).@*RESULTS@#During a median follow-up of 45 months, there were nine (21.4%) deaths in the R-CHOP group and two (4.8%) in the DA-EPOCH-R group. Kaplan-Meier analysis showed statistically significant improvements in PFS and OS in patients with DA-EPOCH-R compared with those treated with R-CHOP (log-rank test, P  = 0.025 and P  = 0.035, respectively). The 2-year PFS and OS rates in the DA-EPOCH-R group were 90.1% (95% confidence interval [CI]: 81.4-99.8%) and 95.2% (95% CI: 89.0-100.0%), respectively, and 80.5% (95% CI: 69.3-93.6%) and 90.5% (95% CI: 52.8-99.8%) in the R-CHOP group. Patients without B symptoms and elevated lactate dehydrogenase levels had a higher PFS in the DA-EPOCH-R group, with P values of 0.038 (hazard ratio [HR]: 0.11; 95% CI: 0.01-0.88) and 0.042 (HR: 0.19; 95% CI: 0.04-0.94), respectively. There were no statistically significant differences in clinical responses and treatment-related toxicities between the two groups.@*CONCLUSION@#Compared with patients received R-CHOP, those treated by DA-EPOCH-R had superior PFS, OS, and controlled toxicity in patients with WR-DLBCL.

A case of duodenal ulcer as prominent manifestation of IgG4-related disease / 北京大学学报(医学版)

A case of IgG4-related disease presented with a duodenal ulcer to improve the understan-ding of IgG4-related diseases was reported. A 70-year-old male presented with cutaneous pruritus and abdominal pain for four years and blackened stools for two months. Four years ago, the patient went to hospital for cutaneous pruritus and abdominal pain. Serum IgG4 was 3.09 g/L (reference value 0-1.35 g/L), alanine aminotransferase 554 U/L (reference value 9-40 U/L), aspartate aminotransferase 288 U/L (reference value 5-40 U/L), total bilirubin 54.16 μmol/L (reference value 2-21 μmol/L), and direct bilirubin 29.64 μmol/L (reference value 1.7-8.1 μmol/L) were all elevated. The abdominal CT scan and magnetic resonance cholangiopancreatography indicated pancreatic swelling, common bile duct stenosis, and secondary obstructive dilation of the biliary system. The patient was diagnosed with IgG4-related disease and treated with prednisone at 40 mg daily. As jaundice and abdominal pain improved, prednisone was gradually reduced to medication discontinuation. Two months ago, the patient developed melena, whose blood routine test showed severe anemia, and gastrointestinal bleeding was diagnosed. The patient came to the emergency department of Beijing Hospital with no improvement after treatment in other hospitals. Gastroscopy revealed a 1.5 cm firm duodenal bulb ulcer. After treatment with omeprazole, the fecal occult blood was still positive. The PET-CT examination was performed, and it revealed no abnormality in the metabolic activity of the duodenal wall, and no neoplastic lesions were found. IgG4-related disease was considered, and the patient was admitted to the Department of Rheumatology and Immunology of Beijing Hospital for further diagnosis and treatment. The patient had a right submandibular gland mass resection history and diabetes mellitus. After the patient was admitted to the hospital, the blood test was reevaluated. The serum IgG4 was elevated at 5.44 g/L (reference value 0.03-2.01 g/L). Enhanced CT of the abdomen showed that the pancreas was mild swelling and was abnormally strengthened, with intrahepatic and extrahepatic bile duct dilation and soft tissue around the superior mesenteric vessels. We pathologically reevaluated and stained biopsy specimens of duodenal bulbs for IgG and IgG4. Immunohistochemical staining revealed remarkable infiltration of IgG4-positive plasma cells into duodenal tissue, the number of IgG4-positive cells was 20-30 cells per high-powered field, and the ratio of IgG4/IgG-positive plasma cells was more than 40%. The patient was treated with intravenous methylprednisolone at 40 mg daily dosage and cyclophosphamide, and then the duodenal ulcer was healed. IgG4 related disease is an immune-medicated rare disease characterized by chronic inflammation and fibrosis. It is a systemic disease that affects nearly every anatomic site of the body, usually involving multiple organs and diverse clinical manifestations. The digestive system manifestations of IgG4-related disease are mostly acute pancreatitis and cholangitis and rarely manifest as gastrointestinal ulcers. This case confirms that IgG4-related disease can present as a duodenal ulcer and is one of the rare causes of duodenal ulcers.

Clinicopathologic characteristics and prognostic analysis of testicular diffuse large B-cell lymphoma / 中华血液学杂志

Objective: To analyze the clinicopathologic characteristics and prognosis of testicular diffuse large B-cell lymphoma (DLBCL) . Methods: A retrospective analysis was performed on 68 patients with testicular DLBCL admitted to Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from October 2001 to April 2020. The gene mutation profile was evaluated by targeted sequencing (55 lymphoma-related genes) , and prognostic factors were analyzed. Results: A total of 68 patients were included, of whom 45 (66.2% ) had primary testicular DLBCL and 23 (33.8% ) had secondary testicular DLBCL. The proportion of secondary testicular DLBCL patients with Ann Arbor stage Ⅲ-Ⅳ (P<0.001) , elevated LDH (P<0.001) , ECOG score ≥ 2 points (P=0.005) , and IPI score 3-5 points (P<0.001) is higher than that of primary testicular DLBCL patients. Sixty-two (91% ) patients received rituximab in combination with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) -based first-line regimen, whereas 54 cases (79% ) underwent orchiectomy prior to chemotherapy. Patients with secondary testicular DLBCL had a lower estimated 5-year progression-free survival (PFS) rate (16.5% vs 68.1% , P<0.001) and 5-year overall survival (OS) rate (63.4% vs 74.9% , P=0.008) than those with primary testicular DLBCL, and their complete remission rate (57% vs 91% , P=0.003) was also lower than that of primary testicular DLBCL. The ECOG scores of ≥2 (PFS: P=0.018; OS: P<0.001) , Ann Arbor stages Ⅲ-Ⅳ (PFS: P<0.001; OS: P=0.018) , increased LDH levels (PFS: P=0.015; OS: P=0.006) , and multiple extra-nodal involvements (PFS: P<0.001; OS: P=0.013) were poor prognostic factors in testicular DLBCL. Targeted sequencing data in 20 patients with testicular DLBCL showed that the mutation frequencies of ≥20% were PIM1 (12 cases, 60% ) , MYD88 (11 cases, 55% ) , CD79B (9 cases, 45% ) , CREBBP (5 cases, 25% ) , KMT2D (5 cases, 25% ) , ATM (4 cases, 20% ) , and BTG2 (4 cases, 20% ) . The frequency of mutations in KMT2D in patients with secondary testicular DLBCL was higher than that in patients with primary testicular DLBCL (66.7% vs 7.1% , P=0.014) and was associated with a lower 5-year PFS rate in patients with testicular DLBCL (P=0.019) . Conclusion: Patients with secondary testicular DLBCL had worse PFS and OS than those with primary testicular DLBCL. The ECOG scores of ≥2, Ann Arbor stages Ⅲ-Ⅳ, increased LDH levels, and multiple extra-nodal involvements were poor prognostic factors in testicular DLBCL. PIM1, MYD88, CD79B, CREBBP, KMT2D, ATM, and BTG2 were commonly mutated genes in testicular DLBCL, and the prognosis of patients with KMT2D mutations was poor.

Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.

Correlation between Serum miR-34a Level and Thrombocytopenia after Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the relationship between serum miR-34a level and thrombocytopenia after chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#A total of 69 eligible DLBCL patients who received chemotherapy in our hospital from January 2018 to January 2020 were prospectively included as the research subjects, all patients received R-CHOP 21 regimen (rituximab + cyclophosphamide + adriamycin + vincristine + prednisone) for chemotherapy, 3 weeks was 1 cycle, and 2 cycles of chemotherapy were used. The patients were divided into a reduction group and a non reduction group according to whether there was thrombocytopenia after chemotherapy, the general data and laboratory indexes of the two groups were investigated and compared, the relationship between serum miR-34a before chemotherapy and thrombocytopenia after chemotherapy in patients was analyzed.@*RESULTS@#Among the 69 DLBCL patients, 36 patients developed thrombocytopenia after 2 cycles of R-CHOP 21 regimen for chemotherapy, the incidence was 52.17%; the level of serum IL-11 and the relative expression of miR-34a mRNA in the reduction group were significantly lower than the non reduction group (P<0.05), compared other data between groups, there was no statistical significant difference (P>0.05); after Logistic regression analysis, the results showed that the level of serum IL-11 and the relative expression of miR-34a mRNA were related to thrombocytopenia after chemotherapy in DLBCL patients, low expression of each index may be a risk factor of thrombocytopenia after chemotherapy in DLBCL patients (OR>1, P<0.05); ROC curve was drawn, and the results showed that the AUC of serum IL-11 level and miR-34a mRNA relative expression before chemotherapy alone and in combination predicted the risk of thrombocytopenia after chemotherapy in DLBCL patients were all >0.80, and the predictive value was ideal, when the cut-off value of serum IL-11 level before chemotherapy was 42.094 pg/ml, and the cut-off value of miR-34a mRNA relative expression was 3.894, the combined prediction value was the best.@*CONCLUSION@#The relative expression of miR-34a mRNA is associated with thrombocytopenia after chemotherapy in DLBCL patients, which may be a risk factor for thrombocytopenia in patients after chemotherapy, has certain value in predicting the risk of thrombocytopenia of patients after chemotherapy.

Rituximab-Based Regimens for Treatment of Primary Gastric Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze clinical response of the Rituximab-based chemotherapy and prognostic features in patients with primary gastric diffuse large B-cell lymphoma (PGDLBCL).@*METHODS@#From June 2008 to December 2020, the data of 53 PGDLBCL patients were analyzed retrospectively.@*RESULTS@#The median age was 46(25-77) years old in 53 patients including 35 males and 18 females. Stomachache is the most common symptom. The diagnosis were confirmed in 47 patients by endoscopic biopsy and 6 patients by surgery. Twenty-six patients had Ⅰ/Ⅱ1 stage (Lugano staging system) disease and 27 cases had II2/IV stage disease. All patients were treated with chemotherapy, including RCHOP (25/53) and R-DA-EPOCH (28/53). Complete remission rate was 79.2%（42/53）. The 3-year and 5-year overall survival (OS) rates were 77.4% and 69.8%. Univariate analysis showed that lactate dehydrogenase(LDH), Lugano stage and lesion size affected OS. Multivariate Cox regression analysis revealed that IPI score and Lugano stage were independent prognosis risk factors affecting OS. The patients in the R-DA-EPOCH group presented better survival outcomes than those in the RCHOP group with late stage (P5-year OS=0.035).@*CONCLUSION@#Rituximab in combination with chemotherapy is the backbone of therapy for PGDLBCL. IPI score and Lugano stage are independent prognosis risk factors affecting OS of PGDLBCL. R-DA-EPOCH can be superior to R-CHOP as a first-line regimen in PGDLBCL patients with late stage.

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases / 北京大学学报(医学版)

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma / 中华肿瘤杂志

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

Clinical analysis of 5 cases of systemic juvenile idiopathic arthritis with coronary artery dilatation / 中华儿科杂志

Objective: To investigate the clinical characteristics of systemic juvenile idiopathic arthritis combined with coronary artery dilatation. Methods: A retrospective analysis was performed on the clinical data, including clinical manifestations, blood routine, inflammatory factors, echocardiography, vascular ultrasound and CT angiography, treatment and outcomes, etc, of 5 cases with systemic juvenile idiopathic arthritis combined with coronary artery dilation admitted to Department of Rheumatology in the affiliated Children's Hospital of Capital Institute of Pediatrics from May 2019 to June 2021. Results: There were 2 males and 3 females among 5 cases. The onset age ranged from 7 months to 4 years 7 months.The diagnostic time ranged from 1.5 months to 3.0 months.Four cases were diagnosed as atypical Kawasaki disease. Three cases showed unilateral coronary artery dilation.Two cases showed bilateral coronary artery dilation.Four cases developed multiple organ injuries.Three cases developed macrophage activation syndrome.Three cases developed lung injury.Two cases developed pericardial effusion.One case developed pulmonary hypertension.As for treatment, 3 cases treated with methylprednisolone pulse therapy and methotrexate combined with cyclosporine, improved after the final application of biological agents, and have stopped prednisone. The other 2 cases were treated with adequate oral prednisone and gradually reduced, and methotrexate was added at the same time, 1 case relapsed in the process of reduction. No other vascular involvement was found in 5 cases. Coronary artery dilation recovered completely after 1 to 3 months of treatment. Conclusions: Systemic juvenile idiopathic arthritis combined with coronary artery dilatation has the clinical characteristics of small onset age, long diagnostic time, prone to multiple organ injuries. Corticosteroids and conventional immunosuppressive agents are not sensitive, and biological agents should be used as soon as possible.The prognosis of coronary artery dilation is good after timely treatment.

Clinical characteristics and prognostic features of 63 HIV-associated diffuse large B-cell lymphoma: a single-center real-world study in China / 中华血液学杂志

Objective: This study aimed to look into the clinical characteristics and prognosis of patients with human immunodeficiency virus (HIV) -associated diffuse large B-cell lymphoma (DLBCL) . Methods: Retrospective review of the clinical data of 63 HIV-infected patients with DLBCL diagnosed at Chongqing University Cancer Hospital between July 2008 and August 2021. The Kaplan-Meier method was used to calculate survival curves, and the log-rank test method was used to compare survival between groups. The Cox proportional hazards model was used for multivariate analysis. Results: In 63 patients with HIV-associated DLBCL, 57 (90.5% ) were men, and the median age was 49 (23-87) years. The most common pathological subtype was the germinal center B-cell-like lymphoma (74.6% ) ; 46.0% (29/63) were combined with extranodal lesions. Seventeen of 63 (27.0% ) patients had large masses (≥7.5 cm) . Twenty of 63 (31.7% ) patients had B symptoms. The median CD4(+) T cell count was 203 (4-1022) ×10(6)/L. A total of 49% (25/51) patients had CD4(+) cell count <200×10(6)/L, 56.9% (33/58) had high (3-5) International Prognostic Index (IPI) scores, and 43.1% (25/58) had low (0-2) IPI scores. Further, 78% (46/59) were diagnosed with Ann Arbor Stage Ⅲ/Ⅳ, and 25.4% (16/63) didn't receive chemotherapy. A total of 22.2% (14/63) of patients received less than four cycles of chemotherapy, and 52.4% (33/63) received four or more cycles of chemotherapy. Among patients undergoing chemotherapy, 61.7% (29/47) received R-CHOP-like regimens, and 38.3% (18/47) used CHOP-like regimens. The 1-, 2-, 3-, and 5-year overall survival (OS) rates were 65.0% , 53.8% , 47.1% , and 43.5% , respectively. Univariate analysis revealed that age ≥ 60 years (P=0.012) , Eastern Cooperative Oncology Gruop Performance Status (ECOG-PS) score 2-4 points (P=0.043) , IPI score 3-5 points (P=0.001) , β(2)-MG elevation (≥5.5 mg/L) (P=0.007) , and systemic chemotherapy cycles less than four times (P<0.001) were the negative prognostic factors affecting the OS of patients. The Cox multivariate analysis depicted that age ≥60 years (HR=2.272, 95% CI 1.110-4.651, P=0.025) , IPI score 3-5 points (HR=3.562, 95% CI 1.794-7.074, P<0.001) , ECOG-PS score 2-4 points (HR=2.675, 95% CI 1.162-6.153, P=0.021) , and number of cycles of chemotherapy<4 (HR=0.290, 95% CI 0.176-0.479, P<0.001) were independent risk factors for adverse prognosis of OS. Conclusion: HIV-associated DLBCL is the most common HIV-related tumor, is most commonly seen in men, and has a high 1-year mortality rate. Chemotherapy combined with antiretroviral therapy can improve patient prognosis.

Proteinosis alveolar pulmonar: reporte de caso en paciente con linfoma no hodgkin mesentérico / Pulmonary alveolar proteinosis: report of a case in patient with history of mesenteric non-hodgkin lymphoma

Objetivos: Exponer en base a un caso clínico una revisión de literatura reciente sobre Proteinosis alveolar pulmonar (PAP). Presentación del caso: Revisión de ficha clínica electrónica de paciente de sexo masculino de 76 años con antecedente de linfoma no Hodgkin (LNH) mesentérico, estirpe B de tipo folicular, quien acude en forma reiterada a servicios de urgencia por cuadro de dos meses de evolución de fiebre, compromiso del estado general y tos. Al examen físico destaca crépitos en hemitórax derecho. Se realizó Tomografía computada (TC) de tórax que mostró opacidades pulmonares en vidrio esmerilado periféricas, con engrosamiento septal liso y algunas bandas retráctiles subpleurales. Se manejó ambulatoriamente con Azitromicina por una semana. Sin respuesta, evoluciona con baja de peso y diaforesis nocturna. Nueva TC de tórax en enero 2021, muestra nuevos focos de "empedrado" periféricos extensos, descrito como "crazy paving", focos de vidrio esmerilado difusos extensos, sin condensación y con resolución de bandas retráctiles. Estudio infeccioso negativo. Se realiza lavado broncoalveolar (LBA) con estudio histológico de líquido que muestra proceso inflamatorio crónico con abundantes macrófagos y material proteináceo. Discusión: Tras el descarte de patología infecciosa, se orientó el estudio hacia otras causas de enfermedad parenquimatosa pulmonar. Así, resulta fundamental la descripción correcta del patrón imagenológico tomográfico y el LBA que resultaron compatibles con PAP. Conclusión: La PAP es una patología infrecuente, pero una historia clínica adecuada, el planteamiento de diagnósticos diferenciales de neumonía de lenta resolución, asociado el reconocimiento del patrón radiológico característico y el estudio histológico con LBA permiten realizar un diagnóstico certero, con gran implicancia terapéutica.

Objective: To present a review of recent literature on pulmonary alveolar proteinosis (PAP) based on a clinical case. Presentation of the case: Review of electronic clinical record of a 76 years-old masculine patient with history of mesenteric Non-Hodgkin Lymphoma (NHL) follicular-type lineage B, who repeatedly attended the emergency services due to a two-month history of symptoms of fever, compromised general condition and cough. Physical examination revealed crepitus in the right hemithorax. Chest computed tomography (CT) was performed, which showed peripheral ground-glass pulmonary opacities, with smooth septal thickening and some subpleural retractile bands. He was managed on an outpatient basis with Azithromycin for one week. No response; evolves with weight loss and night diaphoresis. New chest CT in January 2021, shows new extensive peripheral "cobblestone" foci, described as "crazy paving", extensive diffuse ground glass foci, without condensation and with resolution of retractile bands. Negative infectious study. Bronchoalveolar lavage (BAL) was performed with a histological study of the fluid showing a chronic inflammatory process with abundant macrophages and proteinaceous material. Discussion: After ruling out infectious pathology, the study was oriented towards other causes of pulmonary parenchymal disease. Thus, the correct description of the tomographic imaging pattern and the BAL that were compatible with PAP are essential. Conclusion: PAP is an infrequent pathology, but an adequate clinical history, the approach to differential diagnoses of slowly resolving pneumonia, associated with the recognition of the characteristic radiological pattern and the histological study with BAL allow an accurate diagnosis to be made, with great therapeutic implications.

Síndrome inflamatorio multisistémico postinfección por SARS-CoV-2: a propósito de un caso clínico / Post SARS-CoV-2 multisystem inflammatory syndrome: a clinical case / Síndrome inflamatória pós-infecção por SARS-CoV-2: relato de caso

En Uruguay, la pandemia por SARS-CoV-2 ha generado menos afectación en pacientes de la edad pediátrica, aumentando el número de casos positivos en este grupo etario de forma proporcional al aumento de la circulación del virus. La forma de presentación es generalmente asintomática o con síntomas respiratorios leves a moderados. El síndrome inflamatorio multisistémico postinfección por SARS-CoV-2 (SIM-C) ha sido descrito como una de las principales complicaciones postinfección. Se describe el primer caso de un paciente con SIM-C en la ciudad de Paysandú, Uruguay. Se trata de un escolar de 6 años que cursó una infección por SARS-CoV-2 un mes previo. Se presenta con un cuadro febril de 4 días de evolución asociado a lesiones de piel e inyección conjuntival y odinofagia, con parámetros inflamatorios elevados y afectación cardiológica. Se traslada a CTI local con buena evolución posterior. El alto índice de sospecha de SIM-C mejora el diagnóstico y en consecuencia la morbimortalidad de la enfermedad.

Summary: In Uruguay, the SARS-CoV-2 pandemic has affected the pediatric population less and the number of positive cases in this age group has increased proportionally to the rise of the virus circulation. The presentation is generally asymptomatic or with mild to moderate respiratory symptoms. Post-Infection Multisystem Inflammatory Syndrome by SARS-CoV-2 (MIS-C) has been described as one of the main post-infection complications. We describe the first case of a patient with MIS-C in the city of Paysandú, Uruguay. It is a 6-year-old schoolboy who had had a SARS-CoV-2 infection a month earlier. He showed a 4-day history of fever associated with skin lesions and conjunctival injection and odynophagia, with high inflammatory parameters and cardiac involvement. He was transferred to a local ICU and had a good subsequent evolution. The high index of suspicion of MIS-C improves the diagnosis and consequently the morbidity and mortality rates of the disease.

No Uruguai, a pandemia de SARS-CoV-2 gerou menos afetação em pacientes pediátricos, e o número de casos positivos nessa faixa etária aumentou proporcionalmente ao aumento da circulação do vírus. A forma de apresentação é geralmente assintomática ou com sintomas respiratórios leves a moderados. A Síndrome Inflamatória Multissistêmica Pós-Infecção por SARS-CoV-2 (MIS-C) tem sido descrita como uma das principais complicações pós-infecção. Descreve-se o primeiro caso de paciente com MIS-C na cidade de Paysandú, Uruguai. Ele é um estudante de 6 anos de idade que tinha tido uma infecção por SARS-CoV-2 um mês antes. Apresentou história de febre de 4 dias associada a lesões cutâneas e hiperemia conjuntival e odinofagia, com parâmetros inflamatórios elevados e envolvimento cardiológico. Foi transferido para uma UTI local com boa evolução posterior. O alto índice de suspeita de MIS-C melhora o diagnóstico e, consequentemente, a morbimortalidade da doença.

IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

Central nervous system international prognostic index impacts overall survival in diffuse large b-cell lymphoma treated with r-chop in a third level cancer center from Mexico: a survey of 642 patients

Background: Central nervous system international prognosis index (CNS-IPI) is validated in European and the USA cancer databases. However, no validation has been done in Mexican population. Objective: The objective of the study was to assess the impact of the CNS-IPI on central nervous system (CNS) relapse and survival in Mexican patients with diffuse large B-cell lymphoma (DLBCL). Methods: In this retrospective analysis, clinical, biochemical, and histological variables and the CNS-IPI were analyzed. Results: Six hundred and forty-two patients with DBLCL were included in the study. The mean ± SD age was 56.8 ± 14.9 years. Most had an ECOG of 0-1: 75% (n = 484) had absence of B-symptoms and advanced disease (clinical stage: III-IV, n = 433, 67.4%). According to the CNS-IPI, almost one-half were in the low-risk category. According to the CNS-IPI, CNS relapse rate was 1.36% (95% CI: 83.2-92.8), 3.1% (95% CI: 132.4-162.8), and 7.4% (95% CI 61-91) for patients in the low-, intermediate-, and high-risk categories, respectively. The median overall survival in the high-risk group (CNS-IPI) was 22 months, and it has not been achieved after 80 months of follow-up for the other groups. Conclusions: CNS-IPI was associated with survival; therefore, we propose its use as a prognostic tool for prospective validation.

Primary myocardial diffuse large B cell lymphoma: report of one case / Linfoma difuso de células grandes miocárdico primario: informe de un caso

ABSTRACT Primary myocardial involvement of Diffuse Large B-Cell lymphoma is extremely rare, accounting for 0.5 % of all lymphomas. We report a 65-year-old male, presenting with an acute cardiac tamponade, which was drained. A pericardial window with myocardial biopsy was carried out, disclosing a diffuse large B cell lymphoma. He received 6 cycles of rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP), without response. Finally, a palliative chemotherapy with gemcitabine plus oxaliplatin was prescribed.

El linfoma difuso de células grandes B, primario del miocardio es muy raro. Presentamos un varón de 65 años que se presentó con un taponamiento cardíaco agudo que fue drenado. La biopsia miocárdica un mostró linfoma difuso de células grandes B, primario de miocardio. El paciente recibió 6 ciclos de quimioterapia con rituximab, ciclofosfamida, vincristina y prednisona sin respuesta. Finalmente se optó por una quimioterapia paliativa con gemcitabina y oxaliplatino.