TIGIT is Frequently Expressed in the Tumor Microenvironment of Select Lymphomas: Implications for Targeted Therapy.

Immune checkpoint inhibitors against Programmed Cell Death Protein 1/Programmed Cell (PD-1/PD-L1) and CTLA-4/B7 axes have had limited success in hematologic malignancies, requiring the need to explore alternative targets such as T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/CD155 to improve durable clinical responses. We undertook this study to investigate the expression profile of TIGIT such that the potential efficacy of TIGIT blockade could be mapped among lymphoma subtypes. We validated an immunohistochemical assay for TIGIT and evaluated its expression in lymphoma and tumor microenvironment (TME) cells in 661 lymphoma/leukemia biopsies. Multiplex immunofluorescence was used for correlation with normal TME cell subsets. Tumor or TME TIGIT-positivity was defined as moderate to strong membrane staining in at least 10% of tumor or TME cells, respectively. TME TIGIT expression was correlated with overall survival and progression-free survival and comparison with PD-L1 expression. In most cases, lymphoma cells were TIGIT-negative except for angioimmunoblastic and peripheral T-cell lymphomas, which showed 91% and 47% positivity, respectively. A high proportion of small B-cell lymphoma and anaplastic large cell lymphoma cases had TIGIT-positive TME cells. Chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TIGIT-negative TME cells showed significantly shorter overall survival ( P =0.04). No other statistically significant differences were found. When TIGIT was expressed in TME cells, there were a comparable number of TIGIT-positive only and dual TIGIT/PD-L1 positive cases except for more TIGIT-positive only cases in CLL/SLL. TIGIT expression shows distinctive profiles among lymphoma subtypes. Chronic lymphocytic leukemia/small lymphocytic lymphoma and anaplastic large cell lymphoma demonstrated high TME TIGIT expression compared with PD-L1, with a high proportion of dual TIGIT and PD-L1-positivity. Our results are likely to contribute to the design and correlative study of therapeutic response in clinical trials targeting TIGIT alone or in combination with PD1/PDL1.

Anemochorous and zoochorous seeds of trees from the Brazilian savannas differ in fatty acid content and composition.

Fatty acids (FAs) stored as triacylglycerols (TAGs) are an important source of carbon and energy for germination and seedling development, particularly for plants with small wind-dispersed seeds, allowing greater efficiency in storing both energy and carbon. These plants should be under strong selection to produce seeds rich in FAs and with large amounts of saturated FAs. Their closely packed single-chain configuration allows greater packing, more carbon and energy per unit mass, and are less costly to produce. Efficient carbon storage would be less crucial for zoochorous species, which can reach much larger seed sizes (mass). We analysed the transesterified FA profile from seeds of 22 anemochorous and zoochorous tree species from the Cerrado savannas of Central Brazil. We tested if seed FA content covaried with seed mass and if anemochorous and zoochorous seeds differed in FA contents and distribution. Fatty acids were an important seed source of carbon and energy for most species. Fifteen different FAs were identified. Oleic, linoleic and linolenic tended to be the predominant unsaturated FAs. Oleic acid corresponded to more than 60 % of the total transesterified FAs in seeds of Kielmeyera coriacea, Qualea dichotoma and Triplaris americana. Linoleic acid corresponded to more than 50 % of total FA in Dalbergia miscolobium, Parkia platycephala and Ferdinandusa elliptica while linolenic acid was the dominant component in Inga cylindrica. Across species, palmitic and stearic were the dominant saturated FAs. The only exception was lauric acid (68 % of total FA) in seeds of Qualea grandiflora. On a log10 scale, as the seed increased in mass, accumulation of FAs tends to proceed at a faster rate in anemochorous species than in zoochorous species. They also became increasingly richer in saturated FAs. Zoochorous species had seed TAGs with higher proportion of polyunsaturated FAs.

Indolent NK-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract - a Report of two Cases of a new Provisional Entity on the World Health Organization Classification of Hematolymphoid Tumors.

Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract is a new provisional entity listed in the structure of the forthcoming fifth edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors. It was first named as "NK-cell enteropathy" and "Lymphomatoid gastropathy" by two independent series a decade ago. Molecular or cytogenetic studies have lent support to the clonal/neoplastic nature of this entity. Herein we add two of such cases that still challenge pathologists and were previously diagnosed as aggressive lymphomas of NK/T derivation.

Comparison of two immunohistochemical staining protocols for ALK demonstrates non-inferiority of a 5A4 clone-based protocol versus an ALK01 clone-based protocol for the diagnosis of ALK + anaplastic large cell lymphoma.

Detection of ALK rearrangement and/or expression of the ALK protein is an essential component in the evaluation of many neoplasms. Variability has been reported in the ability of different antibody clones to detect ALK expression. The ALK01 clone is commonly used to detect ALK expression in ALK-positive anaplastic large cell lymphoma (ALK + ALCL). However, this clone has been shown to lack sensitivity when used for solid tumors. The aim of this study was to determine if our high-sensitivity 5A4-based immunohistochemistry protocol is non-inferior to our ALK01-based protocol for the detection of ALK expression in ALK + ALCL. To compare the two protocols, we stained tissue microarrays of 126 hematolymphoid neoplasms and an additional 21 primary cutaneous ALK-negative anaplastic large cell lymphomas with both protocols. All 28 ALK + ALCL samples that were positive for the ALK01 antibody were also positive for the 5A4 clone. Three cases on the tissue microarray that were negative with the ALK01 antibody were clearly positive with the 5A4 antibody. We subsequently stained whole tissue sections of these three cases with the ALK01 antibody and found that these three cases were indeed positive with the ALK01 protocol, suggesting that the absence of staining on the tissue microarray samples was due to a combination of sampling error as well as a dimmer signal with the ALK01 protocol. Our study demonstrates that our 5A4-based protocol is non-inferior to the ALK01 antibody for the diagnosis of ALK-positive anaplastic large cell lymphoma, thus allowing our laboratory to discontinue the use of the ALK01-based protocol.

Environmental Monitoring for Enteroviruses in Maputo, Mozambique-2018.

Due to the possibility of wild poliovirus importation from endemic regions and the high circulation of vaccine-derived poliovirus type 2 in the African region, Mozambique implemented a surveillance program to monitor the circulation of enteroviruses in the environment. From January to November 2018, a period that immediately preceded the cVDPV outbreak in Africa, 63 wastewater samples were collected from different areas in Maputo city. A total of 25 samples (39.7%) were positive based on cell culture isolation. Non-polio enteroviruses were found in 24 samples (24/25; 96%), whereas 1 Sabin-related poliovirus was isolated. Neither wild nor vaccine-derived poliovirus was detected. High circulation of EVB species was detected. Environmental surveillance in the One Health approach, if effectively applied as support to acute flaccid paralysis, can be a powerful aid to the public health system to monitor poliovirus besides non-polio enteroviruses in polio-free areas.

Differences in the metabolic and functional mechanisms used to tolerate flooding in Guazuma ulmifolia (Lam.) from flood-prone Amazonian and dry Cerrado savanna populations.

Flood tolerance is crucial to the survival of tree species subject to long periods of flooding, such as those present in the Amazonian várzea. Tolerance can be mediated by adjustments of metabolism, physiology and morphology, reinforcing the need to investigate the physiological and biochemical mechanisms used by tropical tree species to survive this stress. Moreover, such mechanisms may vary between populations that are subjected to differences in the frequency of flooding events. Here, we aimed to identify the mechanisms used by two populations of the tropical tree Guazuma ulmifolia (Lam.) to tolerate flooding: an Amazonian population frequently exposed to flooding and a Cerrado population, adapted to a dry environment. Young plants were subjected to a flooding of the roots and lower stem for 32 days, followed by 17 days of recovery. Amazonian plants exhibited greater increases in shoot length and higher maximum photosynthetic rate (Amax) compared with non-flooded plants from 7 days of flooding onwards, whereas increased Amax occurred later in flooded Cerrado plants and was not accompanied by increased shoot length. Lactate accumulated in roots of Cerrado plants after 24 h flooding, together with transcripts coding for lactate dehydrogenase in roots of both Cerrado and Amazonian plants. After 7 days of flooding, lactate decreased and alcohol dehydrogenase activity increased transiently, together with concentrations of alanine, γ-aminobutyric acid and succinate, indicating activation of metabolic processes associated with low oxygen availability. Other amino acids also increased in flooded Cerrado plants, revealing more extensive metabolic changes than in Amazonian plants. Wetland and dryland populations of G. ulmifolia revealed the great capacity to tolerate flooding stress through a suite of alterations in photosynthetic gas exchange and metabolism. However, the integrated physiological, biochemical and molecular analyses realized here indicated that wetland plants acclimatized more efficiently with increased shoot elongation and more rapid restoration of normal metabolism.

Use of tigecycline at a teaching hospital / Uso da tigeciclina em hospital de ensino

INTRODUCTION: Tigecycline is an antimicrobial agent, approved for the treatment of complicated skin and soft tissue infections, hospital-acquired and community-acquired pneumonia, intra-abdominal infections and anaerobic or atypical infections. OBJECTIVE: To describe the use of tigecycline in a teaching hospital and to compare data from patients who had their prescriptions audited by the hospital infection committee with those who did not have audited prescriptions. METHODS: Retrospective observational cohort study conducted at a teaching hospital from April 2012 to March 2014 including patients who received tigecycline. Demographic variables, comorbidities, microbiological findings, prescribed antibiotics and technical opinions issued by the Hospital Infection Control Service were collected. RESULTS: 71 patients were included, aged between 13 and 92 years, 63.4% were male and 56.3% were non-white. Tigecycline was the first antimicrobial choice in 19.7% (14/71) of the cases, while the use associated with other antibiotics was observed in 66.2% (45/71) of the prescriptions. mainly with meropenem (28.9%). Empirical use was performed in 69.0% of cases, after culture and the antibiogram in 31.0% and off label use in 81.7%. The microorganisms frequently identified by the culture tests were Enterococcus faecalis (17.6%), Pseudomonas aeruginosa (14.7%) and Klebsiella penumoniae (11.8%). CONCLUSION: The study demonstrated that empirical and off label use is common in clinical practice and few prescriptions were guided by the results of the culture and the antibiogram, demonstrating the need for prescribers to evaluate the benefits/ risks of using this antibiotic, risk of resistance, adverse effects and drug interactions, in addition to cost.

INTRODUÇÃO: A tigeciclina é agente antimicrobiano, aprovada para o tratamento de infecções complicadas na pele e tecidos moles, pneumonia hospitalar e adquirida na comunidade, infecções intra-abdominal e infecções anaeróbias ou atípicas. OBJETIVO: Descrever o uso da tigeciclina em hospital de ensino e comparar dados de pacientes que tiveram suas prescrições auditadas pela comissão de infecção hospitalar com os que não tiveram prescrições auditadas. MÉTODOS: Estudo de coorte retrospectivo observacional realizado em hospital de ensino de abril de 2012 a março de 2014 incluindo pacientes que receberam tigeciclina. Foram coletadas variáveis ​​demográficas, comorbidades, achados microbiológicos, antibióticos prescritos e pareceres técnicos emitidos pelo Serviço de Controle de Infecção Hospitalar. RESULTADOS: Foram incluídos 71 pacientes, com idade entre 13 e 92 anos, 63,4% eram do sexo masculino e 56,3% eram não brancos. A tigeciclina foi primeira escolha antimicrobiana em 19,7% (14/71) dos casos, enquanto o uso associado a outros antibióticos foi observado em 66,2% (45/71) das prescrições. principalmente com meropenem (28,9%). O uso empírico foi realizado em 69,0% dos casos, após cultura e o antibiograma em 31,0% e o uso off label em 81,7%. Os microrganismos frequentemente identificados pelos testes de cultura foram Enterococcus faecalis (17,6%), Pseudomonas aeruginosa (14,7%) e Klebsiella penumoniae (11,8%). CONCLUSÃO: O estudo demonstrou que o uso empírico e off label é comum na prática clínica e poucas prescrições foram orientadas pelos resultados da cultura e do antibiograma, demonstrando necessidade de prescritores avaliarem os benefícios/riscos do uso desse antibiótico, risco de resistência, efeitos adversos e interações medicamentosas, além do custo.

Epidemiological characteristics and adherence of a cohort of elderly people with HIV/AIDS in the Public Health System.

OBJECTIVE: To characterize the epidemiological profile of patients aged 50 years or older diagnosed as HIV/AIDS, in a Specialized Service of the Public Health System. METHODS: A retrospective cohort study using secondary data from medical records in the period 2014 to 2018. Sociodemographic and clinical characteristics, and features related to treatment adherence were organized in a database. Quantitative variables were expressed as mean (or median) ± standard deviation (or interquartile range), and categorical variables expressed as number and percentage of patients. The Kaplan-Meier method was applied to assess the probability of overall specific survival. RESULTS: Of the 241 initially eligible patients, 149 patients were evaluated, registering 19 deaths in the studied period. There was a predominance of males aged 50-59 years, with severe immunodeficiency upon admission (29.7%), and with a CD4+ T lymphocyte count below 200 cells in 62 (46.3%) of patients. Elderly people aged 61 or over were more adherent. There was an increase in the CD4+ T lymphocyte count by an average of 139.63 in the first 6 months, and 50.51 from the first 6 months to 12 months of follow-up, with an average increase in the first 12 months of 157.63 cells. Specific overall survival in the period was 85%. CONCLUSION: Patients older than 50 years had an immune response and no viral load detection in the 12-month period, deserving further studies to improve survival.

Epidemiological characteristics and adherence of a cohort of elderly people with HIV/AIDS in the Public Health System

ABSTRACT Objective To characterize the epidemiological profile of patients aged 50 years or older diagnosed as HIV/AIDS, in a Specialized Service of the Public Health System. Methods A retrospective cohort study using secondary data from medical records in the period 2014 to 2018. Sociodemographic and clinical characteristics, and features related to treatment adherence were organized in a database. Quantitative variables were expressed as mean (or median) ± standard deviation (or interquartile range), and categorical variables expressed as number and percentage of patients. The Kaplan-Meier method was applied to assess the probability of overall specific survival. Results Of the 241 initially eligible patients, 149 patients were evaluated, registering 19 deaths in the studied period. There was a predominance of males aged 50-59 years, with severe immunodeficiency upon admission (29.7%), and with a CD4+ T lymphocyte count below 200 cells in 62 (46.3%) of patients. Elderly people aged 61 or over were more adherent. There was an increase in the CD4+ T lymphocyte count by an average of 139.63 in the first 6 months, and 50.51 from the first 6 months to 12 months of follow-up, with an average increase in the first 12 months of 157.63 cells. Specific overall survival in the period was 85%. Conclusion Patients older than 50 years had an immune response and no viral load detection in the 12-month period, deserving further studies to improve survival.

Hepatotoxicity associated with the use of teriflunomide in a patient with multiple sclerosis: A case report.

RATIONALE: Teriflunomide is an inhibitor of pyrimidine synthesis available as a first-line treatment for relapsing-remitting multiple sclerosis. Drug-induced liver damage is a relevant problem in clinical practice, representing a frequent cause of treatment discontinuation. This case report describes the occurrence of liver injury, with a 33.7-fold increase in the upper limit of normality of the liver enzyme alanine aminotransferase during treatment with teriflunomide 14 mg. PATIENT CONCERN: A 44-year-old woman receiving teriflunomide 14 mg for the treatment of multiple sclerosis presented symptoms suggestive of liver dysfunction 54 days after starting treatment. The patient had no history of using disease-modifying therapy, neither previous liver disease nor other comorbidities. DIAGNOSTICS: The suggested diagnosis was drug-induced liver injury, classified as hepatocellular. Other possible hepatic and autoimmune etiologies were ruled out. INTERVENTIONS: Replacement of teriflunomide treatment with glatiramer acetate and follow-up of the disease. OUTCOMES: Signs and symptoms regressed after treatment with teriflunomide 14 mg was discontinued, with normalization of liver enzyme activity in ∼5 months. The causality assessment of the adverse drug reaction was determined by the Naranjo scaling system, resulting in probable, with a final score of 7. CONCLUSIONS: Teriflunomide-induced liver injury in patients with multiple sclerosis is a serious adverse reaction. The report of this case contributes to updating knowledge about the safety aspects of treatment with teriflunomide and planning of monitoring strategies and patient risk management.

IgG4-related Disease: a diagnostic challenge.

Immunoglobulin IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with a characteristic histopathological appearance that can affect almost any organ. The clinical features result from a focal or diffuse appearance of a tumor-like swelling of the affected organs, identified by physical and/or imaging examination. Herein, we report the case of a 38-year-old male complaining of a worsening chronic right lumbar pain associated with legs and scrotum edema. He also had itchy and erythematous cutaneous lesions on the abdominal wall over the last 8 months, and complained of a diffuse and mild to moderate abdominal discomfort. On examination, the liver was firmly enlarged and tender. His legs had 2+ symmetrical pitting edema extending from his feet to just above the knees. An abdominal computed tomography scan showed a large mass (10 x 8 x 4cm) involving the abdominal infrarenal aorta and the iliac arteries, and compressing the inferior vena cava, with dilated iliac veins, raising the possibility of lymphoproliferative disease. During the initial investigation, the laboratory workup revealed anemia, without other marked changes. A laparoscopic-guided biopsy of the peri-aortic mass was undertaken. The histological report associated with IgG4 immunoglobulin measurement rendered the diagnosis of IgG4-RD. The patient had a favorable outcome after the use of glucocorticoids with the abdominal mass remission.

Medication discrepancies in transition of care of hospitalised children in Brazil: a multicentric study.

OBJECTIVE: To determine the incidence of medication discrepancies in transition points of care of hospitalised children. DESIGN: A prospective observational multicentre study was carried out between February and August 2019. Data collection consisted of the following steps: sociodemographic data collection, clinical interview with the patient's caregiver, review of patient prescriptions and evaluation of medical records. Medication discrepancies were classified as intentional (documented or undocumented) and unintentional. In addition, discrepancies identified were categorised according to the medication discrepancy taxonomy. Unintentional discrepancies were assessed for potential clinical harm to the patient. SETTING: Paediatric clinics of four teaching hospitals in Brazil. PATIENTS: Children aged 1 month-12 years. FINDINGS: A total of 248 children were included, 77.0% (n=191) patients had at least one intentional discrepancy; 20.2% (n=50) patients had at least one unintended discrepancy and 15.3% (n=38) patients had at least one intentional discrepancy and an unintentional one. The reason for the intentional discrepancy was not documented in 49.6% (n=476) of the cases. The most frequent unintentional discrepancy was medication omission (54.1%; n=66). Low potential to cause discomfort was found in 53 (43.4%) unintentional discrepancies, while 55 (45.1%) had the potential to cause moderate discomfort and 14 (11.5%) could potentially cause severe discomfort. CONCLUSIONS: Although most medication discrepancies were intentional, the majority of these were not documented by the healthcare professionals. Unintentional discrepancies were often related to medication omission and had a potential risk of causing harm to hospitalised children.

Reconstrução microcirúrgica de mandíbula com retalho osteocutâneo de fíbula, com auxílio de modelo 3D, em paciente vítima de trauma: relato de caso / Mandible microsurgical reconstruction with osteocutaneous fibular flap, with the assistance of a 3D model, in a trauma patient: case report

Trata-se de um relato de caso de reconstrução microcirúrgica de mandíbula com retalho osteocutâneo de fíbula em um paciente de 16 anos, vítima de agressão com projétil de arma de fogo e trauma contuso em face, acarretando em fratura cominutiva de mandíbula, com perda de elementos dentários e lesões extensas de partes moles. Após tratamento da fase aguda, optou-se pela reconstrução microcirúrgica com retalho livre de fíbula, devido à extensão do defeito mandibular e possibilidade de reabilitação dentária. O uso de modelos tridimensionais da mandíbula e fíbula foram excepcionalmente úteis para tornar possível o melhor planejamento cirúrgico das áreas de osteotomia, com diminuição do tempo de isquemia do retalho da cirurgia.

This is a case report of the mandible microsurgical reconstruction with osteocutaneous fibular flap in a 16-year-old patient. A victim of an assault with a firearm projectile and blunt trauma to the face, resulting in a comminuted mandible fracture, loss of dental elements, and extensive soft tissue injuries. After treatment of the acute phase, we chose microsurgical reconstruction with a free fibula flap due to the mandibular defect's extension and the possibility of dental rehabilitation. The use of three-dimensional models of the mandible and fibula was exceptionally helpful in making the best surgical planning of the osteotomy areas, decreasing the surgery flap's ischemia time.

Association of clinical epidemiological factors to polypharmacy among patients with multiple sclerosis: real-life data / Associação de fatores clínicos epidemiológicos à polifarmácia em pacientes com esclerose múltipla: dados da vida real

INTRODUCTION: Treatment for multiple sclerosis should focus on relapse prevention and treatment, as well as symptom and disease progression control, which require the use of multiple medications. OBJECTIVE: To evaluate the association of polypharmacy and related clinical, epidemiological factors in multiple sclerosis patient cohorts. METHODS: It was conducted a prospective study of multiple sclerosis patients that held a prescription of disease-modifying drugs between January and December 2017. The medications were analyzed and classified as either long-term or as-needed medications for therapeutic objective and prescription status purposes. RESULTS: During 2017, 124 patients were attended, 106 were eligible for the study, and 81 agreed to participate. The average age was 40.95±11.69 years. The disease duration varied between 6 months and 30 years, with a median of 7 years. More than half of the multiple sclerosis patients suffered from comorbidities (54.32%), and 76.54% were categorized as polypharmacy. The comparison of polypharmacy between the groups yielded significant differences for comorbidities and employment status and regarding age between patients with polypharmacy and patients without polypharmacy of long-term medications. CONCLUSION: The age of the patient and the presence of comorbidities are important factors related to polypharmacy.

INTRODUÇÃO: O tratamento da esclerose múltipla deve ser concentrado na prevenção e tratamento de recaídas, bem como no controle da progressão dos sintomas e doenças, o que requer o uso de vários medicamentos. OBJETIVO: Avaliar a associação de polifarmácia a fatores epidemiológicos clínicos em uma coorte de pacientes com esclerose múltipla. MÉTODOS: Foi realizado um estudo prospectivo de pacientes com esclerose múltipla que possuíam prescrição de medicamentos modificadores da doença entre janeiro e dezembro de 2017. Os medicamentos foram analisados e classificados como medicamentos de longo prazo ou conforme necessário para fins terapêuticos de objetivo e status de prescrição. RESULTADOS: Durante 2017 foram atendidos 124 pacientes, destes 106 pacientes foram elegíveis para o estudo e 81 concordaram em participar. A idade média foi de 40,95±11,69 anos. A duração da doença variou entre 6 meses e 30 anos, com mediana de 7 anos. Mais da metade dos pacientes com esclerose múltipla apresentava comorbidades (54,32%) e 76,54% foram classificados com polifarmácia. A comparação da polifarmácia entre os grupos demonstrou diferenças significativas para comorbidades, e situação de trabalho, e em relação à idade entre pacientes com polifarmácia e pacientes sem polifarmácia com medicamentos de longa duração. CONCLUSÃO: A idade do paciente e a presença de comorbidades são fatores importantes relacionados à polifarmácia.

Genetic Subtypes of Systemic Anaplastic Large Cell Lymphoma Show Distinct Differences in PD-L1 Expression and Regulatory and Cytotoxic T Cells in the Tumor Microenvironment.

Anaplastic large cell lymphomas (ALCL) encompass several subgroups that differ in their clinical presentation, genetic features, and prognosis. We characterized the genetic subgroups of 74 patients with ALCL and correlated programmed death ligand 1 (PD-L1) protein expression and compared the densities and ratios of FOXP3+ T regulatory cells and CD8+ tumor-infiltrating lymphocytes (TILs) in tumor cells and the immune microenvironment. The subgroups included anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and ALK-negative (ALK-) ALCL and DUSP22-rearranged and nonrearranged ALK- ALCL. None of our cases represented the TP63-rearrangement ALK- ALCL subgroup. Our results showed that ALK+ ALCL had a higher expression of PD-L1 in the tumor cells, in contrast to ALK- ALCL, which expressed high PD-L1 in tumor-associated macrophages (TAMs). DUSP22-rearranged ALK- ALCL lacked PD-L1 expression in the tumor cells and instead expressed PD-L1 only in TAMs. There was a significant positive correlation of PD-L1 expression between tumor and TAMs in ALK+ ALCL with a negative correlation in ALK- ALCL. Systemic ALCL subgroups had similar densities of CD8+ tumor-infiltrating lymphocytes and FOXP3 T regulatory cells, but differences were observed in the ratio of CD8/FOXP3. Our results suggest that alterations in tumor microenvironment and immune responses exist among systemic ALCL subgroups and these features may account for different clinical behavior and prognosis.

Clinicopathologic and microenvironmental analysis of primary cutaneous CD30-positive lymphoproliferative disorders: a 26 year experience from an academic medical center in Brazil.

BACKGROUND: Primary cutaneous CD30+ lymphoproliferative disorders (pc-CD30-LPD) are a group of clonal T cell lymphoproliferative disorders that despite very similar tumor histology follow different and characteristic clinical courses, suggesting a homeostatic role of the tumor microenvironment. Little is known about tumor microenvironment and there is almost no literature about PD-L1 expression in pc-CD30-LPD. METHODS: This retrospective study presents a fully clinicopathologically characterized series of pc-CD30-LPDs from an academic medical center in Brazil, including 8 lymphomatoid papulomatosis (LyP), 9 primary cutaneous anaplastic large cell lymphoma (pcALCL) and 4 borderline lesions. All the cases were scored for FOXP3+ regulatory T-cells (Treg) and CD8+ cytotoxic tumor infiltrating lymphocytes (TIL) densities, as well as PD-L1 expression in tumor cells and tissue associated macrophages. The CD8+/FOXP3+ ratio was also evaluated. RESULTS: Among the 21 cases of pc-CD30-LPD, PD-L1 expression is frequent in both tumor cells and tissue associated macrophages in pc-CD30-LPD across categories, suggesting that the PD-L1 axis may be a common feature of pc-CD30-LPDs. While reactive T cell infiltrates vary widely from case to case, a common feature across pc-CD30-LPDs is higher density of CD8 than FOXP3 + T cells. The distribution of T cells within the lesions however differed between LyP and pcALCL: we found that LyP lesions tend to be permeated by CD8+ and FOXP3+ T cells, whereas pcALCL tend to be surrounded by a rim of CD8+ TIL and FOXP3+ Tregs with relatively lower density infiltrates in the center of the lesion. CONCLUSIONS: LyP has a trend to have denser immune cells throughout the lesion, with higher FOXP3+ Treg and CD8+ TIL in the center than the edge comparing with pcALCL. PD-L1+ is frequent in tumor cells and tissue associated macrophages in pc-CD30-LPD. The differential distribution of CD8+ and FOXP3+ TILs in LyP as compared to pcALCL could provide a clue to the relapsing/remitting course of LyP as compared to the less frequent spontaneous regression of pcALCL.

Cobertura de lesões em pé e terço inferior da perna com retalho fasciocutâneo reverso da panturrilha (Carriquiry) / Coverage of the lower third of the limb and foot injuries using reverse sural fasciocutaneous flap described by Carriquiry

Introdução: Lesões no terço distal dos membros inferiores, com exposição de ossos, articulações, tendões e vasos sanguíneos, não são passíveis do uso de enxertos de pele. Isto ocorre porque o leito vascular é exíguo e pela pobre granulação das feridas, podendo apenas ser corrigidas com retalhos musculares, miocutâneos, fasciocutâneos ou transferência microcirúrgica. Métodos: O retalho em seu limite inferior é demarcado a partir de 5 cm acima dos maléolos. Superiormente, é marcado num comprimento suficiente para cobertura total da lesão. Realizada incisão em demarcação prévia, e elevados pele e tecido subcutâneo juntamente com a fáscia muscular. O nervo sural é preservado em seu leito original. A elevação do retalho se dá até o ponto inferior marcado (o pedículo). Neste ponto, o retalho é transposto numa angulação suficiente para alcançar a lesão. Resultados: Oito casos foram operados utilizando o retalho descrito. Todos apresentavam exposição de ossos e tendões em região distal da perna, dorso do pé ou ambos, nos quais foram utilizados o retalho fasciocutâneo reverso da perna com a técnica proposta por Carriquiry. Os casos apresentaram resultados estético e funcional satisfatórios. Conclusão: O retalho utilizado se presta à correção de lesões do terço inferior da perna e do pé. É relativamente fácil de ser confeccionado, com bom suprimento vascular, e não há perda funcional do leito doador.

Introduction: Skin grafts are not effective to cover lesions in the distal third of the lower limbs that expose the bones, joints, tendons, and blood vessels due to a limited vascular bed and poor granulation of the wounds. These lesions can only be corrected with microsurgical transfer or muscle, myocutaneous, or fasciocutaneous flaps. Methods: The lower border of the flap was marked 5 cm above the malleolus. The upper border was marked after providing sufficient length for complete coverage of the lesion. The incision was performed at the marked upper border, and the skin and subcutaneous tissue were elevated together with muscle fascia. The sural nerve was preserved in its original bed. The flap was lifted to the marked lower border (the pedicle). At this point, the flap was transposed at a sufficient angle to cover the lesion. Results: Eight cases of surgery were conducted using the flap described above. All cases had exposed bones and tendons in the distal region of the limb, back of the foot, or both, in which the reverse sural fasciocutaneous flap with the technique proposed by Carriquiry was used. The cases showed satisfactory esthetic and functional results. Conclusion: The used flap can correct lesions of the lower third of the limbs and foot. It is relatively easy to make, with good vascular supply, and there is no functional loss of the donor area.

Retalho retroauricular ilhado para reconstrução parcial de orelha: relato de casos / Retroauricular island flap for partial ear reconstruction: case reports

Defeitos parciais de orelha podem ser tratados de diversas formas, dentre elas o fechamento primário, cicatrização por segunda intenção ou retalhos. Diversas opções técnicas foram descritas para a sua reconstrução de modo a manter o contorno natural da orelha, sem sacrificar tecido sadio ou alterar sua estética e função. Apresentamos neste artigo dois casos atendidos no Instituto do Câncer do Hospital de Base de São José do Rio Preto de reconstrução de defeitos condrocutâneos de orelha após ressecção de carcinoma basocelular em região central da orelha, com a confecção de retalho retroauricular ilhado transposto através de uma janela cartilaginosa e com o pedículo desepidermizado. Área doadora com fechamento primário. Tal procedimento constitui técnica segura, pois a região retroauricular é ricamente vascularizada, é de fácil execução, em único estágio e com resultado estético e funcional satisfatório.

Partial ear defects can be treated in several ways, including primary closure, healing by secondary intention, or flaps. Several surgical options have been described for reconstruction in order to maintain the natural contour of the ear, without sacrificing healthy tissues or changing the aesthetics and function. In this article, we present two cases of reconstruction of chondrocutaneous defects of the ear after resection of basal cell carcinoma in the central region of the ear, with the production of a retroauricular island flap transposed through a cartilaginous window with the de-epidermized pedicle. The donor area healed following a primary closure. This procedure can be performed in a single stage, yields satisfactory aesthetic and functional results, and is safe because the retroauricular region is richly vascularized.