BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We sear...BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.展开更多
AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to i...AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.展开更多
AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cerv...AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.展开更多
Objective To determine the effects of combined administration of furosemide and kanamycin on inner ear structures and the auditory nerve in rats. Methods The rats in the treatment group received intravenous injections...Objective To determine the effects of combined administration of furosemide and kanamycin on inner ear structures and the auditory nerve in rats. Methods The rats in the treatment group received intravenous injections of combined furosemide and kanamycin sulfate, and the rats in the normal control group received no treatment. The auditory brainstem response (ABR) test was carried out 7 days after drug administration to determine the effects of drug administration on hearing. Cochlear slice and cochlear wholcmount were prepared after 7 days of drug treatment. Results After 7 days of drug administration, ABR thresholds were significantly higher in the treatment group than in the control group and neurofilaments were significantly reduced, although the number of spiral ganglia showed no decrease and there were no signs of supporting cell injury. Conclusions Combined administration of furosemide and kanamyein sulfate has an apparent synergistic ototoxic effect. Although spiral ganglion damage may not be apparent within a short time period of drug administration, damage to auditory nerve fibers is obvious.展开更多
Heart failure(HF)is a condition of cardiac dysfunction and fluid overload.Neurohormonal activation via the reninangiotensin-aldosterone system and the sympathetic nervous system are the pathophysiological cornerstones...Heart failure(HF)is a condition of cardiac dysfunction and fluid overload.Neurohormonal activation via the reninangiotensin-aldosterone system and the sympathetic nervous system are the pathophysiological cornerstones.[1]Furthermore,HF is a disorder widely associated with grave adverse outcomes and poor prognosis.[2]A loop diuretic is the fundamental drug used to prevent multiorgan failure and improve symptoms in these patients.[3]展开更多
Patients with renal disease are at risk of fluid overload which escalates as the disease progresses. In the present study, we evaluated the efficacy of sequential combination diuretic-therapy (SCDT) in management of m...Patients with renal disease are at risk of fluid overload which escalates as the disease progresses. In the present study, we evaluated the efficacy of sequential combination diuretic-therapy (SCDT) in management of massive fluid overload in Furosemide-refractory renal patients. The added diuretics were Spironolactone 25 mg daily for 3 days, to those without risk of hyperkalemia, followed by Hydrochlorothiazide 25 mg/Metolazone 5 mg daily for 3 more days. Excluded patients were those with 1) acute renal disease, 2) echocardiographic evidence of: a) left ventricular ejection fraction < 40%, b) significant stenotic or incompetent valvular disease, c) ASD or VSD, d) significant pericardial disease, and 3) significant limb venous disease or on drugs likely to cause limb-oedema. To assess the extent of fluid overload;clinical examination was complemented with radiological imaging as well as echocardiographic measurement of systolic pulmonary arterial pressure (sPAP). SCDT led to significant symptomatic, clinical, and radiological improvement of fluid overload without significant side effects. The latter were limited to hyperkalemia and hyponatremia which improved with dietary compliance. Moreover, hyperkalemia improved after subsequent addition of Thiazide/Metolazone. SCDT led to significant (p < 0.001) increase in fractional excretion of sodium and decrease in body weight and sPAP. In conclusion;SCDT is a safe and efficacious measure to control fluid overload in patients with renal diseases.展开更多
AIM: To evaluate the daily high-dose induction therapy with interferon-α2b (IFN-α2b) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on ...AIM: To evaluate the daily high-dose induction therapy with interferon-α2b (IFN-α2b) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS: Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin (1 000-1 200 mg/d) for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 (IFN-α2b 3MU/TIW+1000-1200 mg ribavirin/daily). RESULTS: The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response (EVR) was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response (EOT) and d0% obtained a sustained viral response (SVR). Patients with no response had a significantly lower response rate than those with a former relapse (SVR 30% vs 53%; P=0.049). Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype (SVR 28% vs7d%; P=0.001). As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION: Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.展开更多
BACKGROUND Mannitol is a hyperosmolar agent and the combination of mannitol and furosemide is a widely used treatment for intracranial pressure control.Considering the hypertonic properties of mannitol to move water o...BACKGROUND Mannitol is a hyperosmolar agent and the combination of mannitol and furosemide is a widely used treatment for intracranial pressure control.Considering the hypertonic properties of mannitol to move water out of intracellular spaces,we hypothesized that mannitol combined with furosemide could relieve focal tissue swelling in refractory lymphedema.CASE SUMMARY A 90-year-old female had been diagnosed with intracranial hemorrhage and received a combination of mannitol and furosemide for intracranial pressure control.Independent of the intracranial hemorrhage,she had refractory lymphedema of the left lower extremity since 1998.Remarkably,after receiving the mannitol and furosemide,the patient’s lower extremity lymphedema improved dramatically.After the mannitol and furosemide were discontinued,the lymphedema worsened in spite of complete decongestive therapy(CDT)and intermittent pneumatic compression treatment(IPC).To identify the presumed effect of mannitol and furosemide on the lymphedema,these agents were resumed,and the lymphedema improved again.CONCLUSION The present case raises the possibility that a combination of mannitol and furosemide might be considered another effective therapeutic option for refractory lymphedema when CDT and IPC are ineffective.展开更多
Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to eva...Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.展开更多
Purpose: To evaluate the anxiety and pain levels of cervical cancer patients undergoing intracavitary multifraction high-dose rate (HDR) brachytherapy, as part of a process to develop guidelines for quality patient-ce...Purpose: To evaluate the anxiety and pain levels of cervical cancer patients undergoing intracavitary multifraction high-dose rate (HDR) brachytherapy, as part of a process to develop guidelines for quality patient-centered care. Methods: Cervical cancer patients (n = 31) undergoingmultiple fraction HDR brachytherapy treatment at the National Institute of Oncology in Rabat (Morocco) completed ratings of pain and anxiety intensity using 11-point verbal analog scales, at 6 key time points over 2 brachytherapy insertion procedures and 4 brachytherapy fractions. Women were evaluated for psychological status at baseline before starting the brachytherapy process using the Hospital Anxiety and Depression Scale (HADS). Scores were grouped as follows: 0 - 7 = normal, 8 - 10 = borderline, 11 - 21 = abnormal. Factors that could affect anxiety levels such as education level, relationship status, number of pregnancies and prior surgical history were documented. Results: Between July and August 2020, 31 women with a median age of 49.6 years were evaluated (range: 27 - 70). The HADS score identified depression in 5 patients (16.1%) and anxiety in 12 patients (38.7%). Throughout both treatment procedures, anticipatory anxiety was reported, with a maximum intensity in the operating room during spinal anesthesia (3.23 ± 1.7) and during applicator insertion (2.97 ± 2.4). Moderate-to-severe anxiety scores were reported in 25.8% and 22.6% of patients respectively. Level of education showed a significant correlation with anxiety scores (p = 0.027). Pain increased significantly during the procedure (p ± 1.4) and applicator removal (4.74 ± 1.5) turned out to be the most painful parts of the procedure. No correlation was found between pain and anxiety levels. Conclusion: Intracavitary multifraction high-dose rate brachytherapy is associated with mild to moderate levels of pain and anxiety, although a subset of patients reported more severe symptoms and may require additional medical and psychological support, with particular emphasis on bed-rest duration and applicator removal. The development of effective interventions (both pharmacological and non-pharmacological) is needed to improve women’s experiences of brachytherapy for locally advanced cervical cancer.展开更多
Treatment-resistant schizophrenia has an extremely negative impact on mental health and social life. If clozapine, the gold standard treatment, fails, there are very few options left. The literature suggests that high...Treatment-resistant schizophrenia has an extremely negative impact on mental health and social life. If clozapine, the gold standard treatment, fails, there are very few options left. The literature suggests that high-dose olanzapine (20 - 60 mg/day) is a possible alternative. We report two cases in which very high doses of olanzapine were administered, with significant clinical improvements above 60 mg/day. Clinical, metabolic and cardiac tolerance was good. This report highlights the usefulness of very-high-dose olanzapine in treatment-resistant schizophrenia. The main hypotheses concerning the psychopharmacological mechanisms of very-high-dose olanzapine are discussed.展开更多
Prednisone is the most common first-line treatment for adult primary immune thrombocytopenia (ITP). However, the best initial therapeutic approach is still a matter of debate. Prior studies have shown that high-dose d...Prednisone is the most common first-line treatment for adult primary immune thrombocytopenia (ITP). However, the best initial therapeutic approach is still a matter of debate. Prior studies have shown that high-dose dexamethasone (HD-DXM) produces a high sustained efficacy not achieved by conventional prednisone therapy. However, the definition of response widely differs between individual reports, and this heterogeneity makes comparison of the efficacy difficult. The aim of our study was to compare the therapeutic outcomes of a conventional dose of prednisone with HD-DXM for adult ITP patients as initial therapy. Thirty patients treated with prednisone and 22 patients treated HD-DXM were retrospectively analyzed. No significant differences between the HD-DXM and prednisone groups were observed for the rates of complete response (68% vs. 70%) and response (18% vs. 17%). However, 1 year probability of sustained response was significantly greater in the HD-DXM group than in the prednisone group (78% vs. 38%;P = 0.008). No adverse events necessitating discontinuation of treatment were observed in either group. Our retrospective analysis showed that initial treatment with HD-DXM produced longer response duration compared to a conventional dose of prednisone. Randomized clinical trials are warranted to establish the optimal initial steroid therapy for adult ITP.展开更多
Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was f...Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking [1] [2]. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases [3]. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies;other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.展开更多
BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events...BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events,including rare but serious neurological complications such as Guillain-Barrésyndrome(GBS).GBS is a potentially life-threatening autoimmune disorder characterized by muscle weakness and paralysis.We present a unique case of pembrolizumab-induced GBS to highlight the importance of recognizing this complication and managing it promptly in patients receiving immune checkpoint inhibitors.CASE SUMMARY A 69-year-old woman with a medical history of hypertension,anxiety,depression,and stage IIIB triple-negative breast cancer treated with pembrolizumab,carboplatin,and paclitaxel,presented to the emergency department with a 1-month history of tingling,lower extremity weakness,and shooting pain.Symptoms progressed to global weakness,ascending paralysis,and double vision.Neurological examination revealed significant lower extremity weakness and sensory deficits.Magnetic resonance imaging of the lumbar spine and cerebrospinal fluid analysis confirmed GBS.Initial treatment with intravenous immunoglobulin led to relapse,requiring additional intravenous immunoglobulin and high-dose glucocorticoids.The patient’s condition improved,pembrolizumab therapy was permanently discontinued,and she was discharged to a rehabilitation facility.CONCLUSION Pembrolizumab can induce GBS,necessitating early recognition,prompt diagnosis,and multidisciplinary management to prevent serious complications.展开更多
基金supported by grants from the National Natural Science Foundation of China (82370378 and 82070388)Taishan Scholar Program of Shandong Province (tsqn202211310)National Natural Science Foundation of Shandong Province (ZR2020MH035)。
文摘BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion therapy.METHODS:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy.The primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately included.Compared with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 months.However,no difference was observed in all-cause mortality at 30 d or 1 year.Additionally,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary reperfusion.In terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) activity.CONCLUSION:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose GIK.Moreover,with a higher incidence of complications such as phlebitis,hyperglycemia,and hypoglycemia.Furthermore,there were no observed survival benefits associated with high-dose GIK.More trials with long-term follow-up are still needed.
基金Supported by First Affiliated Hospital,Guangxi Medical University
文摘AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.
基金Supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.2017R1D1A1B03035047the National Research Foundation of Korea Grant funded by the Korean Government,No.NRF-2017M2A2A4A03083634
文摘AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.
基金supported by grants from the Major State Basic Research Development Program of China(973 Program)(#2011CBA01000)National Hi-Tech Research and Development Program of China(863 Program)(#2007AA02Z150)to SMY+1 种基金the National Natural Science Foundation of China(NSFC)(#30871398,30730040,30628030)to SMYNational Eleventh Scientific Program(2008BAI50B08,2007BAI18B12,2007BAI18B14)to SMY
文摘Objective To determine the effects of combined administration of furosemide and kanamycin on inner ear structures and the auditory nerve in rats. Methods The rats in the treatment group received intravenous injections of combined furosemide and kanamycin sulfate, and the rats in the normal control group received no treatment. The auditory brainstem response (ABR) test was carried out 7 days after drug administration to determine the effects of drug administration on hearing. Cochlear slice and cochlear wholcmount were prepared after 7 days of drug treatment. Results After 7 days of drug administration, ABR thresholds were significantly higher in the treatment group than in the control group and neurofilaments were significantly reduced, although the number of spiral ganglia showed no decrease and there were no signs of supporting cell injury. Conclusions Combined administration of furosemide and kanamyein sulfate has an apparent synergistic ototoxic effect. Although spiral ganglion damage may not be apparent within a short time period of drug administration, damage to auditory nerve fibers is obvious.
基金the Swedish Heart-Lung Foundation and the Swedish SUS Funds。
文摘Heart failure(HF)is a condition of cardiac dysfunction and fluid overload.Neurohormonal activation via the reninangiotensin-aldosterone system and the sympathetic nervous system are the pathophysiological cornerstones.[1]Furthermore,HF is a disorder widely associated with grave adverse outcomes and poor prognosis.[2]A loop diuretic is the fundamental drug used to prevent multiorgan failure and improve symptoms in these patients.[3]
文摘Patients with renal disease are at risk of fluid overload which escalates as the disease progresses. In the present study, we evaluated the efficacy of sequential combination diuretic-therapy (SCDT) in management of massive fluid overload in Furosemide-refractory renal patients. The added diuretics were Spironolactone 25 mg daily for 3 days, to those without risk of hyperkalemia, followed by Hydrochlorothiazide 25 mg/Metolazone 5 mg daily for 3 more days. Excluded patients were those with 1) acute renal disease, 2) echocardiographic evidence of: a) left ventricular ejection fraction < 40%, b) significant stenotic or incompetent valvular disease, c) ASD or VSD, d) significant pericardial disease, and 3) significant limb venous disease or on drugs likely to cause limb-oedema. To assess the extent of fluid overload;clinical examination was complemented with radiological imaging as well as echocardiographic measurement of systolic pulmonary arterial pressure (sPAP). SCDT led to significant symptomatic, clinical, and radiological improvement of fluid overload without significant side effects. The latter were limited to hyperkalemia and hyponatremia which improved with dietary compliance. Moreover, hyperkalemia improved after subsequent addition of Thiazide/Metolazone. SCDT led to significant (p < 0.001) increase in fractional excretion of sodium and decrease in body weight and sPAP. In conclusion;SCDT is a safe and efficacious measure to control fluid overload in patients with renal diseases.
文摘AIM: To evaluate the daily high-dose induction therapy with interferon-α2b (IFN-α2b) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-totreat patient group. METHODS: Seventy patients were enrolled in this study. Treatment was started with 10 NU IFN-α2b daily for 3 wk, followed by IFN-α2b 5 NU/TIW in combination with ribavirin (1 000-1 200 mg/d) for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 (IFN-α2b 3MU/TIW+1000-1200 mg ribavirin/daily). RESULTS: The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response (EVR) was achieved in 60% of patients. Fifty percent of all patients achieved an end-oftreatment response (EOT) and d0% obtained a sustained viral response (SVR). Patients with no response had a significantly lower response rate than those with a former relapse (SVR 30% vs 53%; P=0.049). Furthermore, lower response rates were observed in patients infected with genotype la/b than in patients with non-1-genotype (SVR 28% vs7d%; P=0.001). As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION: Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.
文摘BACKGROUND Mannitol is a hyperosmolar agent and the combination of mannitol and furosemide is a widely used treatment for intracranial pressure control.Considering the hypertonic properties of mannitol to move water out of intracellular spaces,we hypothesized that mannitol combined with furosemide could relieve focal tissue swelling in refractory lymphedema.CASE SUMMARY A 90-year-old female had been diagnosed with intracranial hemorrhage and received a combination of mannitol and furosemide for intracranial pressure control.Independent of the intracranial hemorrhage,she had refractory lymphedema of the left lower extremity since 1998.Remarkably,after receiving the mannitol and furosemide,the patient’s lower extremity lymphedema improved dramatically.After the mannitol and furosemide were discontinued,the lymphedema worsened in spite of complete decongestive therapy(CDT)and intermittent pneumatic compression treatment(IPC).To identify the presumed effect of mannitol and furosemide on the lymphedema,these agents were resumed,and the lymphedema improved again.CONCLUSION The present case raises the possibility that a combination of mannitol and furosemide might be considered another effective therapeutic option for refractory lymphedema when CDT and IPC are ineffective.
基金supported by the National Natural Science Foundation of China(No.81700147 and No.82070172).
文摘Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.
文摘Purpose: To evaluate the anxiety and pain levels of cervical cancer patients undergoing intracavitary multifraction high-dose rate (HDR) brachytherapy, as part of a process to develop guidelines for quality patient-centered care. Methods: Cervical cancer patients (n = 31) undergoingmultiple fraction HDR brachytherapy treatment at the National Institute of Oncology in Rabat (Morocco) completed ratings of pain and anxiety intensity using 11-point verbal analog scales, at 6 key time points over 2 brachytherapy insertion procedures and 4 brachytherapy fractions. Women were evaluated for psychological status at baseline before starting the brachytherapy process using the Hospital Anxiety and Depression Scale (HADS). Scores were grouped as follows: 0 - 7 = normal, 8 - 10 = borderline, 11 - 21 = abnormal. Factors that could affect anxiety levels such as education level, relationship status, number of pregnancies and prior surgical history were documented. Results: Between July and August 2020, 31 women with a median age of 49.6 years were evaluated (range: 27 - 70). The HADS score identified depression in 5 patients (16.1%) and anxiety in 12 patients (38.7%). Throughout both treatment procedures, anticipatory anxiety was reported, with a maximum intensity in the operating room during spinal anesthesia (3.23 ± 1.7) and during applicator insertion (2.97 ± 2.4). Moderate-to-severe anxiety scores were reported in 25.8% and 22.6% of patients respectively. Level of education showed a significant correlation with anxiety scores (p = 0.027). Pain increased significantly during the procedure (p ± 1.4) and applicator removal (4.74 ± 1.5) turned out to be the most painful parts of the procedure. No correlation was found between pain and anxiety levels. Conclusion: Intracavitary multifraction high-dose rate brachytherapy is associated with mild to moderate levels of pain and anxiety, although a subset of patients reported more severe symptoms and may require additional medical and psychological support, with particular emphasis on bed-rest duration and applicator removal. The development of effective interventions (both pharmacological and non-pharmacological) is needed to improve women’s experiences of brachytherapy for locally advanced cervical cancer.
文摘Treatment-resistant schizophrenia has an extremely negative impact on mental health and social life. If clozapine, the gold standard treatment, fails, there are very few options left. The literature suggests that high-dose olanzapine (20 - 60 mg/day) is a possible alternative. We report two cases in which very high doses of olanzapine were administered, with significant clinical improvements above 60 mg/day. Clinical, metabolic and cardiac tolerance was good. This report highlights the usefulness of very-high-dose olanzapine in treatment-resistant schizophrenia. The main hypotheses concerning the psychopharmacological mechanisms of very-high-dose olanzapine are discussed.
文摘Prednisone is the most common first-line treatment for adult primary immune thrombocytopenia (ITP). However, the best initial therapeutic approach is still a matter of debate. Prior studies have shown that high-dose dexamethasone (HD-DXM) produces a high sustained efficacy not achieved by conventional prednisone therapy. However, the definition of response widely differs between individual reports, and this heterogeneity makes comparison of the efficacy difficult. The aim of our study was to compare the therapeutic outcomes of a conventional dose of prednisone with HD-DXM for adult ITP patients as initial therapy. Thirty patients treated with prednisone and 22 patients treated HD-DXM were retrospectively analyzed. No significant differences between the HD-DXM and prednisone groups were observed for the rates of complete response (68% vs. 70%) and response (18% vs. 17%). However, 1 year probability of sustained response was significantly greater in the HD-DXM group than in the prednisone group (78% vs. 38%;P = 0.008). No adverse events necessitating discontinuation of treatment were observed in either group. Our retrospective analysis showed that initial treatment with HD-DXM produced longer response duration compared to a conventional dose of prednisone. Randomized clinical trials are warranted to establish the optimal initial steroid therapy for adult ITP.
文摘Recent studies have described the combination of both pulmonary emphysema and idiopathic interstitial lung disease (ILDs) by means of high-resolution computed axial tomography (HRCT). Definition of this syndrome was first named by Cottin as combined pulmonary fibrosis and emphysema (CPFE). Functional and radiological findings have showed that these patients are suffering from severe breathlessness, but whose pulmonary functional tests revealed no signs of obstruction, normal static lung volumes, and depressed DLco, most with a history of smoking [1] [2]. The radiological and endoscopic studies especially show that these patients have both areas of upper-lobe predominant emphysema and lesions compatible with fibrosis in both lung bases [3]. No prior research has reported any cases of such condition in person with no prior history of smoking as well as long-term high-dose of glucocorticoid therapy. In this case report, we discuss the presentation, diagnosis, and management of a 53-year-old non-smoker with increasing shortness of breath with a long-term high-dose of glucocorticoid therapy discovered to have an abnormal variant or presentation of CPFE. The cause of disease was attributed to a certain history of smoking in most studies;other potential risk factors have yet to be properly analyzed. This clinical report features a special case about the problem and solution surrounding this issue.
文摘BACKGROUND The programmed cell death protein 1 inhibitor pembrolizumab has become a key treatment for various cancers,including triple-negative breast cancer.However,it is associated with immune-related adverse events,including rare but serious neurological complications such as Guillain-Barrésyndrome(GBS).GBS is a potentially life-threatening autoimmune disorder characterized by muscle weakness and paralysis.We present a unique case of pembrolizumab-induced GBS to highlight the importance of recognizing this complication and managing it promptly in patients receiving immune checkpoint inhibitors.CASE SUMMARY A 69-year-old woman with a medical history of hypertension,anxiety,depression,and stage IIIB triple-negative breast cancer treated with pembrolizumab,carboplatin,and paclitaxel,presented to the emergency department with a 1-month history of tingling,lower extremity weakness,and shooting pain.Symptoms progressed to global weakness,ascending paralysis,and double vision.Neurological examination revealed significant lower extremity weakness and sensory deficits.Magnetic resonance imaging of the lumbar spine and cerebrospinal fluid analysis confirmed GBS.Initial treatment with intravenous immunoglobulin led to relapse,requiring additional intravenous immunoglobulin and high-dose glucocorticoids.The patient’s condition improved,pembrolizumab therapy was permanently discontinued,and she was discharged to a rehabilitation facility.CONCLUSION Pembrolizumab can induce GBS,necessitating early recognition,prompt diagnosis,and multidisciplinary management to prevent serious complications.