Neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma: The need for patient-centered research

Pancreatic ductal adenocarcinoma is an aggressive cancer with high recurrence rates following surgical resection.While adjuvant chemotherapy improves survival,a significant proportion of patients are unable to initiate or complete all intended therapy following pancreatectomy due to postoperative complications or poor performance status.The administration of chemotherapy prior to surgical resection is an alternative strategy that ensures its early and near universal delivery as well as improves margin-negative resection rates and potentially improves long-term survival outcomes.Neoadjuvant therapy is increasingly being recommended to patients with pancreatic ductal adenocarcinoma,however,patient-centered research on its use is lacking.In this review,we highlight opportunities to focus research efforts in the domains of patient preferences,patient-reported outcomes,patient experience,and survivorship.Novel research in these areas may identify relevant barriers and facilitators to the use of neoadjuvant therapy thereby increasing its utilization,improve shareddecision making for patients and providers,and optimize the experience of those undergoing neoadjuvant therapy.     

Role of cytokines in the progression of renal damage in IgA nephropathy

Summary: IgA nephropathy, or Berger's disease (IgAN), is a worldwide disease which is characterized by a slowly progressive loss of renal function accompanied by decreasing kidney size with the development of glomerulosclerosis and interstitial fibrosis. Immunologic and non-immunologic factors are implicated in the progression of renal damage, since they are potent inducers in stimulating glomerular, tubular and interstitial cells and non-resident cells to produce free oxygen radicals, cytokines, growth factors, chemokines, etc. Recent data from our laboratory and other groups, synthesized in this review, have demonstrated the remarkable involvement of these humoral factors in the progression of renal damage in IgAN patients. Therefore, prospective therapeutic approaches have been suggested in blocking the inflammatory mediators during the pathophysiologic sequelae of immune and non-immune mechanisms which may intervene in the outcome of the disease.     

KGF-transfected cells can stimulate growth and proliferation of human cultured keratinocytes in vitro

Objective: To establish two stably KGF-transfected, immortalized cell lines. Methods: HaCaT-keratinocytes and KMST-6-fibroblasts were transfected by liposome mediated gene transfer. Transfection effectivity, gene integration and configuration of the transgenic protein were investigated by ELISA, DANN-PCR and β-Gal-staining. Results: Most effective GF producing clones were tested by a colorimetric XTT-test. Conclusion: This is a significant acceleration of cell proliferation and mitosis of human keratinocytes in an Air Liquid Interface (ALI) test system.     

Solitary pulmonary nodules: CT assessment

Computed tomography (CT) was used to examine 634 solitary pulmonary nodules (SPNs). Each lesion was assessed as benign or indeterminate on the basis of CT criteria. Benign nodules made up 44% of all SPNs and 58% of the 431 that were 2 cm or less in diameter. All malignant SPNs were assessed as indeterminate, and adenocarcinoma (42%) was the most common primary malignancy. A total of 176 (63% of benign SPNs) were correctly assessed as benign by CT. Ninety SPNs assessed as diffusely calcified were not so identified by conventional tomography at outside institutions. An SPN can be reliably assessed by CT as benign if it exhibits high attenuation values, exceeding a critical level and distributed diffusely throughout a CT section through the center of the lesion and a well-defined edge. Although 38 of 283 (13.4%) primary lung cancers contained localized calcification, there was no significant overlap with the diffuse calcification of benign lesions. Central carcinoid tumors may contain focal ossification, but such lesions may be recognized by noting the proximity of larger bronchi. Assessment of SPNs by CT is most effective for lesions 2.0 cm or less in diameter. For larger lesions, the frequency of benign disease was decreased (14.3% of 203), as was the percentage of benign SPNs correctly assessed as benign by CT (37.9%).     

黑翠碱甲和黑翠碱乙的化学结构

从黑水翠雀(Delphinium potaninii W.T.Wang)根中分得2个新的牛扁碱型C₁₉-二萜生物碱(I和II),由光谱分析(¹HNMR,¹³CNMR和MS)和化学方法,确定碱I为黑翠碱甲(potanidineA)、碱II为黑翠碱乙(potanidineB)。     

Snake bites by the jararacucu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in Sao Paulo State, Brazil

The jararacucu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in Sao Paulo State, Brazil. We examined 29 cases of proven jararacucu bites recruited over a 20-year period in two Sao Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care- unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination.      

Loading-induced changes in synovial fluid affect cartilage metabolism

The purpose of this study was to determine whether changes in the synovial fluid (SF) induced by in vivo loading can induce an alteration in the metabolic activity of chondrocytes in vitro. Therefore, SF was collected from ponies after a period of box rest and after they had exercise for a week. Normal, unloaded articular cartilage explants were cultured in 20% solutions of these SFs for 4 days and chondrocyte activity was determined by glycosaminoglycan (GAG) turnover. In explants cultured in post-exercise SF, GAG synthesis was enhanced and GAG release was diminished when compared to cultures in pre-exercise SF. SF analysis showed that levels of insulin-like growth factors (IGF- I and IGF-II) tended to be higher in post-exercise SF, while no differences were found in metalloproteinase activity, hyaluronic acid and protein concentrations. This study showed that anabolic effects of joint loading on cartilage are, at least partially, mediated by alterations in the SF.      

Surface markers of human eosinophils

Peripheral blood eosinophils from patients with eosinophilia and from healthy subjects were studied for surface immunoglobulins, receptors for the Fc region of IgG, complement receptors, and spontaneous rosette formation with sheep and mouse erythrocytes. Eosinophils were found to have receptors for complement and for aggregated IgG, and to have the same two types of complement receptors as do lymphocytes and monocytes. Immune adherence type receptors were specific for C4 or C3b, while C3d receptors were specific for C3d but unreactive with C4. Eosinophils differed from fully mature neutrophils in that the former had C3d receptors and relatively weak immune adherence (C4 or C3b) receptors, while the later did not have the C3d receptors and had strong immune adherence receptors. Eosinophil phagocytosis of complement-receptor bound erythrocytes was dependent on the presence of IgG in the antibody coating the red blood cells; this requirement for IgG resembled that found in neutrophil phagocytosis. No surface Ig or spontaneous erythrocyte rosette formation was observed with eosinophils.