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BACKGROUND: KEYNOTE-522 demonstrated statistically significant improvements in pathological complete response (pCR) with neoadjuvant pembrolizumab plus chemotherapy and event-free survival (EFS) with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Prior studies have shown the prognostic value of the residual cancer burden (RCB) index to quantify the extent of residual disease after neoadjuvant chemotherapy. In this preplanned exploratory analysis, we assessed RCB distribution and EFS within RCB categories by treatment group. PATIENTS AND METHODS: A total of 1174 patients with stage T1c/N1-2 or T2-4/N0-2 TNBC were randomized 2 : 1 to pembrolizumab 200 mg or placebo every 3 weeks given with four cycles of paclitaxel + carboplatin, followed by four cycles of doxorubicin or epirubicin + cyclophosphamide. After surgery, patients received pembrolizumab or placebo for nine cycles or until recurrence or unacceptable toxicity. Primary endpoints are pCR and EFS. RCB is a prespecified exploratory endpoint. The association between EFS and RCB was assessed using a Cox regression model. RESULTS: Pembrolizumab shifted patients into lower RCB categories across the entire spectrum compared with placebo. There were more patients in the pembrolizumab group with RCB-0 (pCR), and fewer patients in the pembrolizumab group with RCB-1, RCB-2, and RCB-3. The corresponding hazard ratios (95% confidence intervals) for EFS were 0.70 (0.38-1.31), 0.92 (0.39-2.20), 0.52 (0.32-0.82), and 1.24 (0.69-2.23). The most common first EFS events were distant recurrences, with fewer in the pembrolizumab group across all RCB categories. Among patients with RCB-0/1, more than half [21/38 (55.3%)] of all events were central nervous system recurrences, with 13/22 (59.1%) in the pembrolizumab group and 8/16 (50.0%) in the placebo group. CONCLUSIONS: Addition of pembrolizumab to chemotherapy resulted in fewer EFS events in the RCB-0, RCB-1, and RCB-2 categories, with the greatest benefit in RCB-2. These findings demonstrate that pembrolizumab not only increased pCR rates, but also improved EFS among most patients who do not have a pCR.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasia Residual , Paclitaxel , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasia Residual/patologia , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Carboplatina/administração & dosagem , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Ciclofosfamida/efeitos adversos , Idoso , Adulto , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Epirubicina/uso terapêutico , Intervalo Livre de Progressão , Quimioterapia Adjuvante/métodos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Método Duplo-CegoRESUMO
@#In 2000, an equine Yamakagashi (Rhabdophis tigrinus) antivenom (Lot 0001) was testmanufactured as an unapproved drug for treatment of Yamakagashi bites. It was stocked on the premise of super-legal use from the viewpoint of emergency health crisis management. The antivenom showed a strong neutralizing ability against the hemorrhagic and coagulation activity of the Yamakagashi venom in its potency test. One vial of the antivenom can effectively neutralize at least about 4 mg of Yamakagashi venom. Its efficacy has also been confirmed in patients with severe cases of R. tigrinus bite that has been used in emergency. In 2020, this antivenom (Lot 0001) has reached 20 years after its production. To evaluate the integrity and potency of the antivenom, quality control, safety and potency tests had been conducted almost every year since 2012. Physical and chemical tests (property test, moisture content test, insoluble foreign matter test, osmotic pressure ratio test, pH test, protein content test, endotoxin test, sterility test) of the antivenom, showed no significant changes throughout the years, when compared to the results immediately after its production in 2000. All the parameters measured were also within the standard values. In animal safety tests (test for absence of toxicity and pyrogen), there was no change in the test results during the storage period and no abnormalities were observed. The potency test (anti-coagulant activity) after 20 years of the product, showed the same potency as those recorded immediately after production. Therefore, in all of the stability monitoring tests conducted so far, the product did not show any significant change compared to the results immediately after production. This confirms the stability of the product during the stockpiling period to the present, that is, 20 years after production.
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@#A traumatic iliacus hematoma is rare and usually occurs in patients after a fall involving a lower back injury. Although the hematoma may compress the femoral nerve causing femoral nerve palsy, the gold standard treatment for this condition has not been established. Here we report transcatheter arterial embolisation as a useful treatment strategy for a traumatic iliacus hematoma.
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Background: The glissonean pedicle approach was introduced by Couinaud and Takasaki in the early 1980s. The key of the glissonean pedicle approach is clamping the pedicle first, secondly confirming the territory, and finally dissecting the liver parenchyma. In this presentation, we introduced our recent refinements of glissonean pedicle approach for liver resection. “Approach to the glissonean pedicles at the hepatic hilus” Couinaud described three approaches to the hepatic hilus. 1) Intra-fascial access (Control method): The conventional dissection at the hilus or within the sheath is referred to as intrafascial access However, dissection performed under the hilar plate is dangerous and surgeons have to consider any variations of the hepatic artery and bile ducts. 2) Extra-fascial access (Glissonean pedicle approach): The glissonean pedicle is dissected from the liver parenchyma at the hepatic hilus before dissecting the liver parenchyma. This procedure prevents intrahepatic metastasis of HCC, which spreads along the portal vein and improves the overall survival after surgery. 3) Extra-fascial and transfissural access: If the main portal fissure or the left suprahepatic fissure is opened after dissecting the liver parenchyma, the surgeon can confirm the pedicles that arise from the hilar plate or the umbilical plate. “Operative techniques” 1) Preoperative 3D simulation of the precise anatomy of portal vein, hepatic artery and bile duct at hepatic hilus should be performed. 2) Right glissonean pedicle: The hilar plate is detached from the quadrate lobe. The assistant pulls the liver parenchyma cranially and the operator conversely pulls the hepatoduodenal ligament caudally. Mayo scissors are inserted along the liver parenchyma between the liver parenchyma and glissonean capsule (Fig.1). Then forceps are inserted in the same way and the right main pedicle is taped (Fig.2). The right anterior and posterior glissonean pedicles are taped as well. 3) Left glissonean pedicle: The hilar plate is detached from the liver parenchyma. Then, the Arantius duct is confirmed and the left pedicle is dissected along the left pedicle at the ventral side of the Arantius duct. “Pitfall of glissonean pedicle approach” The right pedicle should be dissected in the liver side as much as possible to prevent the injury of left hepatic duct. If possible, the right pedicle is recommended to be dissected at the level of the second branches separately (Fig.3). The right posterior hepatic duct sometimes branches from the left hepatic duct and the Arantius duct is confirmed and the left pedicle should be dissected along the left pedicle at the ventral side of the Arantius duct because the right posterior hepatic duct branches from the left hepatic duct at the dorsal side of Arantius’ duct. In addition, the intraoperative cholangiogram should be used in the case with the abnormal anatomy of bile duct. Conclusions: Any anatomical hepatectomy can be performed using “glissonean pedicle approach” which allows simple, safe and easy liver resection.
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During routine investigations, we are surprised to find that therapy for bone metastases is sometimes delayed for a considerable period of time. To determine the extent of this delay and its causes, we reviewed the medical records of symptomatic patients seen at our hospital who had been recently diagnosed as having bone metastases for the last four years. The treatment delay was defined as the interval between presentation with symptoms and definitive treatment for bone metastases. The diagnostic delay was defined as the interval between presentation with symptoms and diagnosis of bone metastases. The results of diagnostic radiological examinations were also reviewed for errors. The study population included 76 males and 34 females with a median age of 66 years. Most bone metastases were diagnosed radiologically. Over 75 percent of patients were treated with radiotherapy. The treatment delay ranged from 2 to 307 days, with a mean of 53.3 days. In 490 radiological studies reviewed, we identified 166 (33.9 percent) errors concerning 62 (56.4 percent) patients. The diagnostic delay was significantly longer for patients with radiological errors than for patients without radiological errors (P < 0.001), and much of it was due to radiological errors. In conclusion, the treatment delay in patients with symptomatic bone metastases was much longer than expected, and much of it was caused by radiological errors. Considerable efforts should therefore be made to more carefully examine the radiological studies in order to ensure prompt treatment of bone metastases
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Humanos , Adulto , Idoso , Pessoa de Meia-Idade , Feminino , Masculino , Neoplasias Ósseas , Erros de Diagnóstico , Idoso de 80 Anos ou mais , Neoplasias Ósseas , Estatísticas não Paramétricas , Fatores de TempoRESUMO
No 50§ Congresso Brasileiro de Dermatologia, realizado em setembro de 1995 em Belém, Pará, foi constituído um grupo de trabalho cujo tema de discussäo foi iatrogenias em dermatologia. Como o tema é muito extenso, foram selecionados pelo coordenador do grupo três assuntos considerados de maior interesse: 1. Iatrogenia no tratamento medicamentoso da acne; 2. Iatrogenia e corticosteróides sistemicos e tópicos; e 3. Iatrogenia em certos procedimentos cosmiátricos. Os relatores fizeram ampla revisäo bibliográfica que foi previamente entregue aos participantes do grupo para discussäo. Durante o congresso os temas foram apresentados pelos relatores e, após, discutidos com o grupo. Neste trabalho será apresentada uma sinopse da discussäo desse grupo.
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Humanos , Acne Vulgar , Corticosteroides/efeitos adversos , Antagonistas de Androgênios , Antibacterianos/uso terapêutico , Cosméticos/efeitos adversos , Doença Iatrogênica/epidemiologia , Isotretinoína , Tetraciclinas/efeitos adversos , Acne Vulgar/induzido quimicamente , RetinoidesRESUMO
Cloning genes for glycosylphosphatydilinositol (GPI)-anchor biosynthesis is important to further understand its mechanisms and regulation. We have been using expression cloning methods in which a cDNA library was transfected into GPI-anchor-deficient mutant cells. The transfectants which restored surface expression of GPI-anchored proteins were isolated and the plasmids were rescued. In this way we previously cloned cDNAs of genes for complementation classes A and F, and named them PIG-A and PIG-F, respectively. In the present study we have cloned the gene for class B, termed PIG-B. In each case we used different methods. For cloning PIG-A cDNA we used a cDNA library made with an Epstein-Barr-virus-based vector and human class A mutant JY5 which expresses EBNA-1 protein. The EBNA-1 protein allows stable replication of oriP-containing plasmids in the episomal form. For cloning PIG-F cDNA we chose a transient expression method and cotransfected a human T-cell cDNA library made with a vector bearing an origin of replication of polyoma virus with a plasmid bearing polyoma virus large T into the class F murine thymona mutant. This cotransfection strategy was unsuccessful for cloning PIG-B due to low transfection efficiency of the class B thymoma mutant SIA-b. Thus, we first established large T-expressing SIA-b cells and then transfected them with cDNA library. PIG-B cDNA restored the surface expression of Thy-1 on SIA-b cells and also synthesis of mature type GPI-anchor precursors in these cells. The cDNA consists of 1929 bp and codes for a putative new protein of 554 amino acid residues
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Humanos , Replicação do DNA , Fosfatidilinositóis/genética , Glicolipídeos/genética , Replicação Viral , Sequência de Aminoácidos , Clonagem Molecular , DNA/biossíntese , Fosfatidilinositóis/biossíntese , Biblioteca Gênica , Glicolipídeos/biossíntese , Hemoglobinúria Paroxística/genética , Herpesvirus Humano 4/fisiologia , MutaçãoRESUMO
Vinte e cinco doentes de psoriase foram tratados com halcinonida creme a 0,1% utilizando curativos plasticos oclusivos apenas a noite, observando-se 84% de bons resultados