Ziv-afilbercept(Zaltrap, Ziv) is a humanized fusion protein constructed by joining the vascular endothelial growth factor(VEGF) binding portions of human VEGF receptors 1 and 2 to the Fc portion of human immunoglobuli...Ziv-afilbercept(Zaltrap, Ziv) is a humanized fusion protein constructed by joining the vascular endothelial growth factor(VEGF) binding portions of human VEGF receptors 1 and 2 to the Fc portion of human immunoglobulin IgG 1. Recently, a randomized, open-label, phase Ⅲ study compared 5-fluorouracil, leucovorin, irinotecan(FOLFIRI)/Ziv with FOLFIRI/placebo in patients who had been previously treated with oxaliplatin based chemotherapy for metastatic colon cancer(mC RC). Patients who had received prior bevacizumab therapy were also eligible. This study showed that the addition of Ziv improved overall survival with median survival time of 13.5 mo vs 12.06 mo in ziv vs placebo arm. Ziv also improved progression free survival from 4.67 mo to 6.9 mo with a response rate of 19.8% in the Ziv/FOLFIRI group vs 11.1% in FOLFIRI alone group. This led to the approval of Ziv in combination with FOLFIRI in metastatic colon cancer patients treated with prior oxaliplatin regimens. The mostcommon side effects were diarrhea, stomatitis, fatigue, hypertension, weight loss, loss of appetite, abdominal pain, and headache. As the use of Ziv has become more widespread in oncology practices, familiarity with the toxicity profile of the drug and the use of practice guidelines for their treatment has become increasing important. This review will address the toxicities noted in trials using Ziv for the treatment of mC RC, and will provide recommendations for toxicity management.展开更多
Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. EDS type Ⅳ, or vascular EDS, is caused by loss-of-function mutations in the type Ⅲ pro-collagen ...Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. EDS type Ⅳ, or vascular EDS, is caused by loss-of-function mutations in the type Ⅲ pro-collagen gene (COL3A1 ). Common complications of EDS type IV include gastrointestinal bleeding and bowel perforations, posing diagnostic and therapeutic dilemmas for both surgeons and gastroenterologists. Here, we describe a complicated case of EDS type Ⅳ in a 35-year-old caucasian female who presented with overt gastro-intestinal bleeding. The patient had a prior history of spontaneous colonic perforation, and an uncomplicated upper endoscopy was performed. A careful ileoscopy was terminated early due to tachycardia and severe ab-dominal pain, and a subsequent computed tomography scan confirmed the diagnosis of ileal perforation. The patient was managed conservatively, and demonstrated daily improvement. At the time of hospital discharge, no further episodes of gastrointestinal blood loss had occurred. This case highlights the benefit of conservative management for EDS patients with gastrointestinal hemorrhage. It is recommended that surgical treatmentshould be reserved for patients who fail conservative treatment or in cases of hemodynamic instability. Finally, this case demonstrates the necessity for a higher threshold of operative or endoscopic interventions in EDS type Ⅳ patients.展开更多
We assessed incidence and outcomes of patients with ventilator-associated respiratory infections (VARI) due to tracheobronchitis (VAT) and pneumonia (VAP), including length of intensive care unit (ICU) stay and ventil...We assessed incidence and outcomes of patients with ventilator-associated respiratory infections (VARI) due to tracheobronchitis (VAT) and pneumonia (VAP), including length of intensive care unit (ICU) stay and ventilator days. We also examined pathogens, rate of progression from VAT to VAP, and impact of antibiotic therapy for VAT. Data analysis included 234 patients, 100 patients (43%) had at least moderate (+++) bacterial growth in their semi-quantitative endotracheal aspirate (SQ-ETA) cultures. VAT and VAP were each diagnosed in 34 (15%) patients. Staphylococcus aureus was the most common pathogen isolated and had the highest rate of progression from VAT to VAP. Seven (21%) of the 34 patients were diagnosed with VAT that later progressed to VAP in averaged 3 days. Patients diagnosed with VAT had significantly more ventilator days (9 vs 6, p p < 0.001) and hospital days (22 vs 17, p < 0.001). No significant difference was observed in the clinical outcomes of the 25 VAT patients with timely, appropriate antibiotics compared to the 9 VAT patients who did not receive timely appropriate antibiotics. VAT was a risk factor for increased ventilator days, longer length of ICU and hospital stay. The time window from VAT to VAP allowed physicians to identify the pathogens and sensitivity profile needed to treat VAT with appropriate antibiotics. Data from well-designed studies were needed to assess the impact of early, appropriate antibiotic therapy for VAT, the choice of antibiotics, as well as the duration and route of administration.展开更多
Objectives This study sought to evaluate the negative predictive value( NPV) of preoperative dobutamine stress echocardiography(DSE) in patients who fail to ac hieve target heart rate(HR) and assess the influence of r...Objectives This study sought to evaluate the negative predictive value( NPV) of preoperative dobutamine stress echocardiography(DSE) in patients who fail to ac hieve target heart rate(HR) and assess the influence of resting wall motion abno rmalities(WMAs) without demonstrable ischemia on perioperative events. Backgroun d The prognostic value of a negative-submaximal DSE study before noncardiac sur gery is unknown. Methods Consecutive patients (n=429) who underwent surgery over a three-year period, preceded by DSE, were included. We compared perioperative event rates among those without inducible ischemia according to whether or not 85%age-adjusted maximum HR was achieved, and whether WMAs were present at rest . Results Of 397 negative DSEs, peak HR was < 85%maximum predicted in 62 (16%) . Most were receiving beta-blockers (77%). The average dobutamine and atropine doses were 48 μg/kg/min and 1.2 mg, respectively. Average HR was 115 beats/min (74%maximum predicted). Perioperative myocardial infarctions occurred more fre quently in patients with positive tests (3 of 32 <<9.4%>> vs. 7 of 397 <<1.8%>>; p =0.03) , but with similar frequency among the negative-maximal and negative-su bmaximal groups(6 of 335, 1.8%vs. 1 of 62, 1.6%, respectively). Accordingly, t he NPV was 98%in both subgroups. Events occurred exclusively in patients with W MAs at rest: 7 of 100 (7%) versus 0 of 297 (0%) (p < 0.0001). Conclusions In p atients undergoing preoperative DSE, failure to achieve target HR is not uncommo n despite an aggressive DSE regimen. A negative DSE without resting WMAs has exc ellent NPV regardless of the HR achieved. Patients with resting WMAs appear to b e at increased risk for perioperative events even without provokable ischemia.展开更多
We describe a patient who developed seropositive myasthenia gravis 16 years after she was diagnosed with autoimmune premature ovarian failure with antibodies to the receptor for follicle stimulating hormone (FSH). Alt...We describe a patient who developed seropositive myasthenia gravis 16 years after she was diagnosed with autoimmune premature ovarian failure with antibodies to the receptor for follicle stimulating hormone (FSH). Although thymectomy led to improvement of her myasthenic symptoms, menses did not resume. Such combined seropositivity for antibodies to acetylcholine and ovarian hormone receptors in a patient with myasthenia gravis and premature ovarian failure may reflect common disease mechanisms, although the precise pathogenesis of these disorders remains ill defined.展开更多
PURPOSE: Recent studies have suggested that a subset of patients with Crohn’s colitis may have a favorable outcome after ileal pouch-anal anastomosis and have advocated elective ileal pouch anal anastomosis in select...PURPOSE: Recent studies have suggested that a subset of patients with Crohn’s colitis may have a favorable outcome after ileal pouch-anal anastomosis and have advocated elective ileal pouch anal anastomosis in selected patients with Crohn’s disease. We have not offered ileal pouch anal anastomosis to patients with known Crohn’s disease, but because of the overlap in clinical presentation of ulcerative colitis and inde terminate colitis, some patients receiving an ileal pouch-anal anastomosis are subsequently found to have Crohn’s disease. We review our experience with these patients to identify potential preoperative predictors of ultimate pouch failur e. METHODS: Patients with a final diagnosis of Crohns disease were identified from an ileal pouch anal anastomosis registry. These patients are followed pros pectively. Preoperative and postoperative clinical and pathologic characteristic s were evaluated as predictors of outcome. Median (range) values are listed. RES ULTS: Thirty two (18 females) patients (4.1 percent) with a final diagnosis of Crohn’s disease were identified from a registry of 790 ileal pouch anal anasto mosis patients (1980-2002). Patients underwent ileal pouch anal anastomosis in two stages (11 patients) or three stages (21 patients). The preoperative diagno sis was ulcerative colitis in 24 patients and indeterminate colitis in 8 patient s. Median follow up was 153 (range, 13-231) months. The median time from ileal pouch anal anastomosis to diagnosis of Crohns disease was 19 (range, 0-188) months. Complications occurred in 93 percent, including perineal abscess/fistul a (63 percent), pouchitis (50 percent), and anal stricture (38 percent). Pouch f ailure (excision or current diversion) occurred in nine patients (29 percent) at a median of 66 (range, 6-187) months. Two of these 9 patients had preoperative anal disease (not significant). Comparing patients with failed pouches (n=9) to patients with functioning pouches (n=23), post ileal pouch anal anastomosis p erineal abscess (67 vs. 26 percent, P=0.05) and pouch fistula (89 vs. 30 percent , P=0.01) were more commonly associated with pouch failure. Preoperative clinica l, endoscopie, and pathologic features were not predictive of pouch failure or p atient outcome. For those with a functional pouch, 50 percent have been or are c urrently on medication to treat active Crohns disease. This group had six bowe l movements in 24 (range, 3-10) hours, with leakage in 60 percent and pad usage in 45 percent. CONCLUSIONS: Patients who undergo ileal pouch anal anastomosis and are subsequently found to have Crohns disease experience significant morbi dity. Preoperative characteristics, including the presence of anal disease, were not predictive of subsequent pouch failure. We choose not to recommend the rout ine application of ileal pouch anal anastomosis in any subset of patients with known Crohns disease.展开更多
文摘Ziv-afilbercept(Zaltrap, Ziv) is a humanized fusion protein constructed by joining the vascular endothelial growth factor(VEGF) binding portions of human VEGF receptors 1 and 2 to the Fc portion of human immunoglobulin IgG 1. Recently, a randomized, open-label, phase Ⅲ study compared 5-fluorouracil, leucovorin, irinotecan(FOLFIRI)/Ziv with FOLFIRI/placebo in patients who had been previously treated with oxaliplatin based chemotherapy for metastatic colon cancer(mC RC). Patients who had received prior bevacizumab therapy were also eligible. This study showed that the addition of Ziv improved overall survival with median survival time of 13.5 mo vs 12.06 mo in ziv vs placebo arm. Ziv also improved progression free survival from 4.67 mo to 6.9 mo with a response rate of 19.8% in the Ziv/FOLFIRI group vs 11.1% in FOLFIRI alone group. This led to the approval of Ziv in combination with FOLFIRI in metastatic colon cancer patients treated with prior oxaliplatin regimens. The mostcommon side effects were diarrhea, stomatitis, fatigue, hypertension, weight loss, loss of appetite, abdominal pain, and headache. As the use of Ziv has become more widespread in oncology practices, familiarity with the toxicity profile of the drug and the use of practice guidelines for their treatment has become increasing important. This review will address the toxicities noted in trials using Ziv for the treatment of mC RC, and will provide recommendations for toxicity management.
文摘Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. EDS type Ⅳ, or vascular EDS, is caused by loss-of-function mutations in the type Ⅲ pro-collagen gene (COL3A1 ). Common complications of EDS type IV include gastrointestinal bleeding and bowel perforations, posing diagnostic and therapeutic dilemmas for both surgeons and gastroenterologists. Here, we describe a complicated case of EDS type Ⅳ in a 35-year-old caucasian female who presented with overt gastro-intestinal bleeding. The patient had a prior history of spontaneous colonic perforation, and an uncomplicated upper endoscopy was performed. A careful ileoscopy was terminated early due to tachycardia and severe ab-dominal pain, and a subsequent computed tomography scan confirmed the diagnosis of ileal perforation. The patient was managed conservatively, and demonstrated daily improvement. At the time of hospital discharge, no further episodes of gastrointestinal blood loss had occurred. This case highlights the benefit of conservative management for EDS patients with gastrointestinal hemorrhage. It is recommended that surgical treatmentshould be reserved for patients who fail conservative treatment or in cases of hemodynamic instability. Finally, this case demonstrates the necessity for a higher threshold of operative or endoscopic interventions in EDS type Ⅳ patients.
文摘We assessed incidence and outcomes of patients with ventilator-associated respiratory infections (VARI) due to tracheobronchitis (VAT) and pneumonia (VAP), including length of intensive care unit (ICU) stay and ventilator days. We also examined pathogens, rate of progression from VAT to VAP, and impact of antibiotic therapy for VAT. Data analysis included 234 patients, 100 patients (43%) had at least moderate (+++) bacterial growth in their semi-quantitative endotracheal aspirate (SQ-ETA) cultures. VAT and VAP were each diagnosed in 34 (15%) patients. Staphylococcus aureus was the most common pathogen isolated and had the highest rate of progression from VAT to VAP. Seven (21%) of the 34 patients were diagnosed with VAT that later progressed to VAP in averaged 3 days. Patients diagnosed with VAT had significantly more ventilator days (9 vs 6, p p < 0.001) and hospital days (22 vs 17, p < 0.001). No significant difference was observed in the clinical outcomes of the 25 VAT patients with timely, appropriate antibiotics compared to the 9 VAT patients who did not receive timely appropriate antibiotics. VAT was a risk factor for increased ventilator days, longer length of ICU and hospital stay. The time window from VAT to VAP allowed physicians to identify the pathogens and sensitivity profile needed to treat VAT with appropriate antibiotics. Data from well-designed studies were needed to assess the impact of early, appropriate antibiotic therapy for VAT, the choice of antibiotics, as well as the duration and route of administration.
文摘Objectives This study sought to evaluate the negative predictive value( NPV) of preoperative dobutamine stress echocardiography(DSE) in patients who fail to ac hieve target heart rate(HR) and assess the influence of resting wall motion abno rmalities(WMAs) without demonstrable ischemia on perioperative events. Backgroun d The prognostic value of a negative-submaximal DSE study before noncardiac sur gery is unknown. Methods Consecutive patients (n=429) who underwent surgery over a three-year period, preceded by DSE, were included. We compared perioperative event rates among those without inducible ischemia according to whether or not 85%age-adjusted maximum HR was achieved, and whether WMAs were present at rest . Results Of 397 negative DSEs, peak HR was < 85%maximum predicted in 62 (16%) . Most were receiving beta-blockers (77%). The average dobutamine and atropine doses were 48 μg/kg/min and 1.2 mg, respectively. Average HR was 115 beats/min (74%maximum predicted). Perioperative myocardial infarctions occurred more fre quently in patients with positive tests (3 of 32 <<9.4%>> vs. 7 of 397 <<1.8%>>; p =0.03) , but with similar frequency among the negative-maximal and negative-su bmaximal groups(6 of 335, 1.8%vs. 1 of 62, 1.6%, respectively). Accordingly, t he NPV was 98%in both subgroups. Events occurred exclusively in patients with W MAs at rest: 7 of 100 (7%) versus 0 of 297 (0%) (p < 0.0001). Conclusions In p atients undergoing preoperative DSE, failure to achieve target HR is not uncommo n despite an aggressive DSE regimen. A negative DSE without resting WMAs has exc ellent NPV regardless of the HR achieved. Patients with resting WMAs appear to b e at increased risk for perioperative events even without provokable ischemia.
文摘We describe a patient who developed seropositive myasthenia gravis 16 years after she was diagnosed with autoimmune premature ovarian failure with antibodies to the receptor for follicle stimulating hormone (FSH). Although thymectomy led to improvement of her myasthenic symptoms, menses did not resume. Such combined seropositivity for antibodies to acetylcholine and ovarian hormone receptors in a patient with myasthenia gravis and premature ovarian failure may reflect common disease mechanisms, although the precise pathogenesis of these disorders remains ill defined.
文摘PURPOSE: Recent studies have suggested that a subset of patients with Crohn’s colitis may have a favorable outcome after ileal pouch-anal anastomosis and have advocated elective ileal pouch anal anastomosis in selected patients with Crohn’s disease. We have not offered ileal pouch anal anastomosis to patients with known Crohn’s disease, but because of the overlap in clinical presentation of ulcerative colitis and inde terminate colitis, some patients receiving an ileal pouch-anal anastomosis are subsequently found to have Crohn’s disease. We review our experience with these patients to identify potential preoperative predictors of ultimate pouch failur e. METHODS: Patients with a final diagnosis of Crohns disease were identified from an ileal pouch anal anastomosis registry. These patients are followed pros pectively. Preoperative and postoperative clinical and pathologic characteristic s were evaluated as predictors of outcome. Median (range) values are listed. RES ULTS: Thirty two (18 females) patients (4.1 percent) with a final diagnosis of Crohn’s disease were identified from a registry of 790 ileal pouch anal anasto mosis patients (1980-2002). Patients underwent ileal pouch anal anastomosis in two stages (11 patients) or three stages (21 patients). The preoperative diagno sis was ulcerative colitis in 24 patients and indeterminate colitis in 8 patient s. Median follow up was 153 (range, 13-231) months. The median time from ileal pouch anal anastomosis to diagnosis of Crohns disease was 19 (range, 0-188) months. Complications occurred in 93 percent, including perineal abscess/fistul a (63 percent), pouchitis (50 percent), and anal stricture (38 percent). Pouch f ailure (excision or current diversion) occurred in nine patients (29 percent) at a median of 66 (range, 6-187) months. Two of these 9 patients had preoperative anal disease (not significant). Comparing patients with failed pouches (n=9) to patients with functioning pouches (n=23), post ileal pouch anal anastomosis p erineal abscess (67 vs. 26 percent, P=0.05) and pouch fistula (89 vs. 30 percent , P=0.01) were more commonly associated with pouch failure. Preoperative clinica l, endoscopie, and pathologic features were not predictive of pouch failure or p atient outcome. For those with a functional pouch, 50 percent have been or are c urrently on medication to treat active Crohns disease. This group had six bowe l movements in 24 (range, 3-10) hours, with leakage in 60 percent and pad usage in 45 percent. CONCLUSIONS: Patients who undergo ileal pouch anal anastomosis and are subsequently found to have Crohns disease experience significant morbi dity. Preoperative characteristics, including the presence of anal disease, were not predictive of subsequent pouch failure. We choose not to recommend the rout ine application of ileal pouch anal anastomosis in any subset of patients with known Crohns disease.
