BACKGROUND Cow's milk allergy(CMA)is a common condition in infants,requiring alternative protein sources in their diets.Soya milk has become a popular substitute,especially in developing countries where it is a mo...BACKGROUND Cow's milk allergy(CMA)is a common condition in infants,requiring alternative protein sources in their diets.Soya milk has become a popular substitute,especially in developing countries where it is a more affordable option compared to expensive hypoallergenic feeds for infants with insufficient breast milk supply.However,recent observations have shown an increase in soya cross-allergic reactions among infants with CMA.AIM To determine how often infants diagnosed with CMA also had soya cross-allergy and to examine the symptoms and outcomes of these infants at 2 years of age.METHODS Data from two pediatric centers were analyzed,looking at clinical records of children under 2 years old diagnosed with CMA from August 2015 to July 2023,divided into two four-year periods.RESULTS The records of 432 infants with CMA were analyzed.In the first four-year period from August 2015 to July 2019,142 infants were studied,with 27(19%)found to have soya-protein allergy as well.In the second four-year period,a total of 290 infants were studied,and soya allergy was found in 136 babies(47%).This represents a significant increase(P<0.0001)in cases of soya protein cross-allergy among infants with CMA.The most common symptoms observed were gastroesophageal reflux disorder(39%),followed by failure to thrive,bloody diarrhea,watery diarrhea,and constipation.At 2 years of age,these infants showed significant growth failure compared to infants with CMA only.CONCLUSION In conclusion,this study emphasizes the importance of being cautious when using soy protein in infants with cow's milk protein allergy,especially in areas where cost is a major concern.展开更多
In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trau...In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trauma can be decreased,and patients’quality of life can be improved by ensuring safety.Herein,we explore the axillary de-escalation surgery model for breast cancer.展开更多
BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of respons...BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic treatment.We present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.CASE SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth failure.Hypoalbuminemia,anemia,and elevated inflammatory markers were also present.Endoscopic assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was made.The patient was initially treated with oral steroids and fistulotomy.After the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of steroids.Clinical and biochemical steroid-free remission was achieved with good trough levels.After 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the disease.CONCLUSION TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production.This strategy could be a good alternative to combination therapy,especially in very young patients.展开更多
AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent fou...AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR)rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%)and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n=16),the p CR rate was 47%(n=8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n=7)and 53%(n=9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.展开更多
Objective:To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy(ADT)in high-risk prostate cancer in three radiotherapy dose groups.Methods:Between 1998 a...Objective:To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy(ADT)in high-risk prostate cancer in three radiotherapy dose groups.Methods:Between 1998 and 2013,patients with high-risk prostate cancer underwent threedimensional conformal radiotherapy or intensity-modulated radiotherapy of 66 Gy,72 Gy,or 78 Gy with ADT.Prostate-specific antigen(PSA)relapse was defined using the Phoenix definition.PSA relapse-free survival(PRFS)was evaluated in each radiotherapy dose group.Moreover,high-risk patients were divided into H-1(patients with multiple high-risk factors)and H-2(patients with a single high-risk factor)as risk subgroups.Results:Two hundred and eighty-nine patients with a median follow-up period of 77.3 months were analyzed in this study.The median duration of ADT was 10.1 months.Age,Gleason score,T stage,and radiotherapy dose influenced PRFS with statistical significance both in univariate and multivariate analyses.The 4-year PRFS rates in Group-66 Gy,Group-72 Gy and Group-78 Gy were 72.7%,81.6%and 90.3%,respectively.PRFS rates in the H-1 subgroup differed with statistical significance with an increasing radiotherapy dose having a more favorable PRFS,while PRFS rates in H-2 subgroup did not differ with increase in radiotherapy dose.Conclusion:Dose escalation for high-risk prostate cancer in combination with ADT improved PRFS.PRFS for patients in the H-1 subgroup was poor,but dose escalation in those patients was beneficial,while dose escalation in the H-2 subgroup was not proven to be effective for improving PRFS.展开更多
Objective： Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer （NSCLC）. Due to absence of phase I trial in China, we conducted this study to define the maximum-to...Objective： Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer （NSCLC）. Due to absence of phase I trial in China, we conducted this study to define the maximum-tolerated dose （MTD） of capecitabine with fixed docetaxel for Chinese patients with previously treated NSCLC. Methods： Previously treated patients with NSCLC were entered into this study. Escalating doses of capecitabine with fixed docetaxel were administered in a modified Fibonacci sequence. The initial doses were capecitabine 625 mg/m2, bid, on days d5-d 18, and docetaxe130 mg/m2 on days 1 and 8, respectively. The regimen was repeated every 21 days. If no dose-limiting toxicity （DLT） was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be one dose level below the level at which DLT appeared. Results： Eighteen patients received 67 cycles at capecitabine of level I （1250 mg/m2, divided into 625 mg/m2, bid） and level II （1500 mg/m2, 750 mg/m2, bid）. The most common toxicities were neutropenia, hand and feet syndrome, fatigue and nausea. Eight DLTs occurred in 5 patients in the whole group, including 1 DLT in dose level I and 7 DLTs in dose level 2. Since 4 of 6 patients in level II experienced DLTs, we declared thus level I was MTD. Cunclusion： MTD of our phase I trial was capecitabine of 1250 mg/m2/d combined with docetaxel of 30 mg/m2/wk. This combination regimen was well tolerated for previously treated patients with NSCLC. The efficacy of this schedule is currently being further evaluated in a prospective phase II trial.展开更多
This paper investigates survivability escalation strategies in multi layers transport networks such as ATM/SDH/WDM networks, and presents oriented failures and oriented traffic escalation mechanisms. Furthermore, W...This paper investigates survivability escalation strategies in multi layers transport networks such as ATM/SDH/WDM networks, and presents oriented failures and oriented traffic escalation mechanisms. Furthermore, We present a new survivability Escalation strategy for SDH Based ATM transport networks, which addresses difficult problem for resources sharing pool(RSP) among different layers restoration mechanisms. In this paper, we also present integer programming (IP) model for the resources sharing pool (RSP) design problem and the node simulation model for escalation Node. The simulation results show that the proposed ESP is very efficient. The proposed model can be easily extended for other types of multi layer networks, such as WDM based ATM networks or WDM based SDH networks.展开更多
Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patien...Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.展开更多
Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤...Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤ 5 cm. Total doses were escalated from 40 to 48, then to 56 Gy, delivered in 4 equal fractions administered 2 to 3 times per week on an IRB approved protocol. SBRT was administered us- ing 5 to 9 fixed beam arrangements with CT loca- lization. Internal target volumes (ITV) were based on breath hold scans or 4D CT simulation. The planning target volume (PTV) was defined as the ITV with a uniform 5 mm expansion. Dose limiting toxicity (DLT) was defined as any grade 3 or higher toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria (CTC). Results: Between April 2004 and February 2008, 18 patients received the prescribed treatment (40 Gy n = 6, 48 Gy n = 7, 56 Gy n = 5). Seventeen of 18 patients had non-small cell lung cancer (1 with rectal cancer), four of whom were treated for an oligometastasis. The median age of the patients was 68, while the median Karnofsky performance status was 90. The mean tumor size was 2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary event occurred (at 48 Gy dose level) immediately following treatment with the onset of fever and shortness of breath that responded to antibiotics. No other DLTs occurred. Conclusions: SBRT utilizing patient specific target volumes without gating appears safe. The maximum tolerated dose was not reached.展开更多
There have been a lot of research exertions and studies to improve the safety of critical infrastructures using the Security Operations Center (SOC). As part of efforts, the purpose of this research is to propose a fr...There have been a lot of research exertions and studies to improve the safety of critical infrastructures using the Security Operations Center (SOC). As part of efforts, the purpose of this research is to propose a framework to automate the SOC’s performance of triage, containment and escalation. The research leveraged on qualitative desk review to collect data for analysis, deduced strengths and weaknesses for the current SOC implementations and used that as a basis for proposing the framework. In view of the constant evolution of SOC operations and capabilities coupled with the huge volumes of data collected for analysis, an efficient framework for SOC operations is proposed. The qualitative analysis is used to deduce strengths and weaknesses for the current SOC implementations as a premise for proposing the framework. It consists of eight interactive stages that further leverage on a proposed algorithm for baselining, remediation and escalation. The result of this research is a proposed framework that serves as a unique contribution to enhancing the SOC’s ability to automatically perform triage, containment and escalation. Supplementary to similar and earlier work reviewed, the framework is proposed as the way forward to automatically enable SOC setups with the capacity to efficiently perform triage of security threats, vulnerabilities and incidents, effectively contain identified breaches and appropriately escalate for prompt and accurate solutions.展开更多
Decompensated liver cirrhosis(DLC)is characterized by severe liver dysfunction and immune dysregulation,posing significant treatment challenges.Mesenchymal stromal cell(MSC)therapy has shown promise in DLC treatment,b...Decompensated liver cirrhosis(DLC)is characterized by severe liver dysfunction and immune dysregulation,posing significant treatment challenges.Mesenchymal stromal cell(MSC)therapy has shown promise in DLC treatment,but the optimal dosing strategies and dose-dependent therapeutic mechanisms in humans remain unclear,limiting its clinical application.We conducted sequential Phase Ia/Ib trials using a single-arm,dose-escalation design to evaluate the safety and tolerability of MSC therapy in DLC patients while also exploring its immunomodulatory effects and gathering preliminary therapeutic signals.展开更多
In an interview with Beijing Review.Einar Tangen,a senior fellow at the Taihe Institute,a Beijing-based think tank,and a seasoned independent economic commentator,shared his views on what the recent tariff pause betwe...In an interview with Beijing Review.Einar Tangen,a senior fellow at the Taihe Institute,a Beijing-based think tank,and a seasoned independent economic commentator,shared his views on what the recent tariff pause between China and U.S.reveals about both sides9 trade strategies,why U.S.tariffs fail to fix trade gaps and whether the 90-day reprieve can lead to lasting solutions.展开更多
In the original publication of our paper,“Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia,”published on Blood Science,2024 Jan;6(1):e00179,we have identified several ...In the original publication of our paper,“Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia,”published on Blood Science,2024 Jan;6(1):e00179,we have identified several errors that require correction.展开更多
Introduction The accuracy of sentinel lymph node biopsy(SLNB)after neoadjuvant therapy(NAT)has been confirmed in clinical nodal stage 1(c N1)patients,and more patients could benefit from axillary surgery de-escalation...Introduction The accuracy of sentinel lymph node biopsy(SLNB)after neoadjuvant therapy(NAT)has been confirmed in clinical nodal stage 1(c N1)patients,and more patients could benefit from axillary surgery de-escalation after NAT(1,2).展开更多
Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug ...Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.展开更多
Objective:To assess the feasibility of dose escalation guided by ^(18)F-deoxyglucose positron emission tomography/computer tomography(^(18)F-FDG PET/CT)for esophageal cancer(EC).Methods and materials:Ten random patien...Objective:To assess the feasibility of dose escalation guided by ^(18)F-deoxyglucose positron emission tomography/computer tomography(^(18)F-FDG PET/CT)for esophageal cancer(EC).Methods and materials:Ten random patients treated with definitive chemoradiotherapy and pre-therapeutic ^(18)FFDG PET/CT were included in this study.Retrospectively,a threshold of 50%of SUVmax was used to define the high FDG uptake region of the GTV(GTVPET).Three intensity-modulated radiation therapy(IMRT)plans were generated,delivering three dose levels to three different planning target volumes(PTVs).50.4 Gy delivered to PTV50.4 was defined on computed tomography(CT)as Plan50.4,63 Gy was delivered to PTV63 was defined as GTV plus a uniform margin of 0.5 cm as Plan63,and 70 Gy delivered to PTV70 was defined as GTVPET plus a 0.5 cm margin as Plan70.A dosimetric comparison was performed based on normal tissue complication probability(NTCP)for the lung and heart.Results:Clinically acceptable dose escalation failed for 2 of 10 patients in Plan63 due to heart dose constraints.One patient failed heart dose constraint for Plan70.Two patients failed spinal cord constraint for Plan63.Three patients failed lung dose constraints for both Plan63 and Plan70,two of which were even not suitable for Plan50.4 for the same reason.NTCP modeling for lung showed increased risk for Plan63 and Plan70 compared to Plan50.4.The difference between Plan63 and Plan70 was insignificant.NTCP modeling for heart showed an increased risk from 6.38%of Plan50.4 to 8.88%of Plan70(P=0.009)or 9.79%of Plan63(P=0.007).The risk of heart mortality was significantly higher for Plan63 than Plan70(P=0.047).Conclusions:Selective boosting of sub-volumes based on ^(18)F-FDG PET/CT is feasible way with a modest increase in the risk of cardiac and lung toxicities.展开更多
We review the evidence for predation of shelly benthic prey over 125 million years of earth history in the James Ross Basin,Antarctica(~65°S).Although poor in the Early Cretaceous lower parts of the sequence,whic...We review the evidence for predation of shelly benthic prey over 125 million years of earth history in the James Ross Basin,Antarctica(~65°S).Although poor in the Early Cretaceous lower parts of the sequence,which represent essentially deeper water facies,evidence for both potential crushers and drillers becomes more apparent in the Santonian–Campanian Santa Marta Formation,and by the Maastrichtian López de Bertodano Formation there is an extensive fossil record of drill holes attributable to naticid gastropods,and some evidence of crushing by decapods crustaceans and possibly other taxa too.This continues at a similar level of intensity across the K/Pg boundary into the Danian Sobral Formation,but is less well constrained in the latest Paleocene–Early Eocene.The most extensive record of predation occurs in the Middle Eocene section of the La Meseta Formation on Seymour Island which also records the highest levels of benthic diversity within the entire basin.This key section is providing some important new evidence to suggest that the rate of acceleration of benthic predation intensity through the Late Mesozoic–Early Cenozoic in the polar regions may be similar to that seen in lower latitude regions.Predator–prey interaction was a key factor in the evolution of polar marine faunas too.展开更多
Constant escalations in the number of diabetics worldwide and the failure of conventional therapy to restore normoglycemia without adverse effects,in spite of tremendous strides in modern medicine,calls for naturopath...Constant escalations in the number of diabetics worldwide and the failure of conventional therapy to restore normoglycemia without adverse effects,in spite of tremendous strides in modern medicine,calls for naturopathy and alternative medicine.Because diabetes is multi-factorial and has secondary complications,prevention of hyperglycemia is the central dogma for its management.To date,no oral hypoglycemic exists which can achieve tight glycemic control without side effects.Dietary adjuncts,lifestyle interventions and a resurgence of interest in phyto-therapy have consequently gained ground.Natural hypoglycemics have attracted attention due to ease of incorporation in everyday diet,affordability,less adverse effects,and long term safety.Ethno botanical literature reports more than 800 anti-diabetic plants species.Eucalyptus is well represented in the Aboriginal Pharmacopoeias for its various pharmacological activities.Its hot aqueous decoction has been used as a hypoglycemic in various regions of world.This editorial attempts to summarize the data on the hypoglycemic potential of the different eucalyptus species,highlight the value of its natural biomolecules for the prophylaxis and treatment of type2 diabetes,describe their mechanistic actions,shed light on the posology and safety aspects of eucalyptusand assess its applicability as a reinforcement to currently used therapy.展开更多
Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTO...Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTOG 0617 trial didn’t show any benefit of dose escalation to 74 Gy. In this unicentric retrospective analysis we compare the RTOG 0617 result with the outcome of our own 74-Gy-NSCLC cohort. Methods and Material: Since October 2009, 80 patients with NSCLC were treated with 74 Gy in 37 fractions, of which 69 patients were eligible for a retrospective analysis of local and distant failure, survival time and treatment related toxicity. A subgroup analysis was done for patients with a possible follow-up of at least 18 month. Results: Complete local remission could be achieved in 18 patients (26.1%);26 patients (37.7%) had a partial remission and 3 patients (4.4%) a stable local disease. Local failure occurred in 12 patients (17.3%). Distant failure occurred in 27 patients (39.1%). The median survival time was 43.7 weeks (95% CI: 25.2 - 62.3 weeks). 5 patients (6.3%) developed RT induced side effects. As for the analyzed subgroup, a complete or partial local remission could be achieved in 29 patients (61.7%). Local failure occurred in 11 patients (23.4%) and 20 patients (42.6%) developed distant metastases. The 18-month overall survival was 38.3% and the median survival time was 51.7 weeks (95% CI: 27.2 - 76.3 weeks). Conclusion: The results of this retrospective analysis indicate that 74 Gy total radiation dose might not lead to results as bad as indicated by the RTOG 0617 trial. It might therefore be a suitable treatment concept for people with NSCLC.展开更多
文摘BACKGROUND Cow's milk allergy(CMA)is a common condition in infants,requiring alternative protein sources in their diets.Soya milk has become a popular substitute,especially in developing countries where it is a more affordable option compared to expensive hypoallergenic feeds for infants with insufficient breast milk supply.However,recent observations have shown an increase in soya cross-allergic reactions among infants with CMA.AIM To determine how often infants diagnosed with CMA also had soya cross-allergy and to examine the symptoms and outcomes of these infants at 2 years of age.METHODS Data from two pediatric centers were analyzed,looking at clinical records of children under 2 years old diagnosed with CMA from August 2015 to July 2023,divided into two four-year periods.RESULTS The records of 432 infants with CMA were analyzed.In the first four-year period from August 2015 to July 2019,142 infants were studied,with 27(19%)found to have soya-protein allergy as well.In the second four-year period,a total of 290 infants were studied,and soya allergy was found in 136 babies(47%).This represents a significant increase(P<0.0001)in cases of soya protein cross-allergy among infants with CMA.The most common symptoms observed were gastroesophageal reflux disorder(39%),followed by failure to thrive,bloody diarrhea,watery diarrhea,and constipation.At 2 years of age,these infants showed significant growth failure compared to infants with CMA only.CONCLUSION In conclusion,this study emphasizes the importance of being cautious when using soy protein in infants with cow's milk protein allergy,especially in areas where cost is a major concern.
基金supported by grants from the Natural Science Foundation of Shandong Province(Grant No.ZR2024QH058).
文摘In the era of precision medicine,the breast cancer surgical treatment field is gradually moving toward a de-escalation model.Through precise preoperative assessments and multidisciplinary decision-making,surgical trauma can be decreased,and patients’quality of life can be improved by ensuring safety.Herein,we explore the axillary de-escalation surgery model for breast cancer.
文摘BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic treatment.We present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.CASE SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth failure.Hypoalbuminemia,anemia,and elevated inflammatory markers were also present.Endoscopic assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was made.The patient was initially treated with oral steroids and fistulotomy.After the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of steroids.Clinical and biochemical steroid-free remission was achieved with good trough levels.After 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the disease.CONCLUSION TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production.This strategy could be a good alternative to combination therapy,especially in very young patients.
文摘AIM:To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost(IMRT-SIB).METHODS:We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIBbased neoadjuvant chemoradiation protocol.During the concurrent chemoradiation therapy,radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume,with a regimen at the discretion of the treating medical oncologist.This was followed by surgical tumor resection.We analyzed pathological completion response(p CR)rates its relationship with overall survival and event-freesurvival.RESULTS:Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis.Among the IMRT-SIB-treated patients,the toxicity appeared mild,the most common side effects were grade 1-3 esophagitis(46%)and pneumonitis(11.7%).There were no cardiac events.The Ro resection rate was 94%(n=16),the p CR rate was 47%(n=8),and the postoperative morbidity was zero.There was one mediastinal failure found,one patient had local failure at the anastomosis site,and the majority of failures were distant in the lung or bone.The 3-year diseasefree survival and overall survival rates were 41%(n=7)and 53%(n=9),respectively.CONCLUSION:The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications.
基金This work was supported in part by the Research and Development Fund of the National Cancer Center and by the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development(AMED)(26-A-18 and 26-A-28).
文摘Objective:To retrospectively investigate the treatment outcomes of external beam radiotherapy with androgen deprivation therapy(ADT)in high-risk prostate cancer in three radiotherapy dose groups.Methods:Between 1998 and 2013,patients with high-risk prostate cancer underwent threedimensional conformal radiotherapy or intensity-modulated radiotherapy of 66 Gy,72 Gy,or 78 Gy with ADT.Prostate-specific antigen(PSA)relapse was defined using the Phoenix definition.PSA relapse-free survival(PRFS)was evaluated in each radiotherapy dose group.Moreover,high-risk patients were divided into H-1(patients with multiple high-risk factors)and H-2(patients with a single high-risk factor)as risk subgroups.Results:Two hundred and eighty-nine patients with a median follow-up period of 77.3 months were analyzed in this study.The median duration of ADT was 10.1 months.Age,Gleason score,T stage,and radiotherapy dose influenced PRFS with statistical significance both in univariate and multivariate analyses.The 4-year PRFS rates in Group-66 Gy,Group-72 Gy and Group-78 Gy were 72.7%,81.6%and 90.3%,respectively.PRFS rates in the H-1 subgroup differed with statistical significance with an increasing radiotherapy dose having a more favorable PRFS,while PRFS rates in H-2 subgroup did not differ with increase in radiotherapy dose.Conclusion:Dose escalation for high-risk prostate cancer in combination with ADT improved PRFS.PRFS for patients in the H-1 subgroup was poor,but dose escalation in those patients was beneficial,while dose escalation in the H-2 subgroup was not proven to be effective for improving PRFS.
基金Supported by a grant of Science and Technology Department of Hebei Province,China(No.072761711)
文摘Objective： Capecitabine combined with docetaxel have demonstrated antitumor synergy for non-small cell lung cancer （NSCLC）. Due to absence of phase I trial in China, we conducted this study to define the maximum-tolerated dose （MTD） of capecitabine with fixed docetaxel for Chinese patients with previously treated NSCLC. Methods： Previously treated patients with NSCLC were entered into this study. Escalating doses of capecitabine with fixed docetaxel were administered in a modified Fibonacci sequence. The initial doses were capecitabine 625 mg/m2, bid, on days d5-d 18, and docetaxe130 mg/m2 on days 1 and 8, respectively. The regimen was repeated every 21 days. If no dose-limiting toxicity （DLT） was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be one dose level below the level at which DLT appeared. Results： Eighteen patients received 67 cycles at capecitabine of level I （1250 mg/m2, divided into 625 mg/m2, bid） and level II （1500 mg/m2, 750 mg/m2, bid）. The most common toxicities were neutropenia, hand and feet syndrome, fatigue and nausea. Eight DLTs occurred in 5 patients in the whole group, including 1 DLT in dose level I and 7 DLTs in dose level 2. Since 4 of 6 patients in level II experienced DLTs, we declared thus level I was MTD. Cunclusion： MTD of our phase I trial was capecitabine of 1250 mg/m2/d combined with docetaxel of 30 mg/m2/wk. This combination regimen was well tolerated for previously treated patients with NSCLC. The efficacy of this schedule is currently being further evaluated in a prospective phase II trial.
文摘This paper investigates survivability escalation strategies in multi layers transport networks such as ATM/SDH/WDM networks, and presents oriented failures and oriented traffic escalation mechanisms. Furthermore, We present a new survivability Escalation strategy for SDH Based ATM transport networks, which addresses difficult problem for resources sharing pool(RSP) among different layers restoration mechanisms. In this paper, we also present integer programming (IP) model for the resources sharing pool (RSP) design problem and the node simulation model for escalation Node. The simulation results show that the proposed ESP is very efficient. The proposed model can be easily extended for other types of multi layer networks, such as WDM based ATM networks or WDM based SDH networks.
文摘Purpose: To study the effect of escalating radiation dose;in intermediate and high risk prostate cancer patients;via online image-guidance on acute toxicities. Patients and Methods: thirty-eight prostate cancer patients were treated by using simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) with online image guided correction via kilo voltage cone beam computed tomography (KV-CBCT)/electronic portal imaging device (EPID) of trans-rectal ultrasound (TRUS)-inserted intraprostatic gold fiduciary markers. High-risk patients received a median dose of 80.5 Gy to prostate and 56 Gy to pelvic nodes in 35 fractions over 7 weeks. Intermediate-risk patients received a similar prostate dose over the same overall treatment time. Acute toxicity (bladder, rectal and bowel symptoms) was reported once weekly during the radiation course and up to 3 months from the end of the radiation course. Results: The image guided (IG)-IMRT allows escalating the radiation dose delivered to the prostate through minimizing the margin of setup error to less than 0.5 cm with subsequent sparing of nearby organs at risk. Out of thirty-eight patients, no patient developed >grade 1 acute rectal toxicity, 7.9% of patients experienced grade 3 urinary toxicity and there was no reported small intestinal toxicity. Conclusion: Escalating the radiation dose more than 80 Gy in intermediate and high risk prostate cancer patients was safe and not associated with grade 3 - 4 RTOG toxicity when guided by online verification of intra-prostatic fiducial markers.
文摘Objectives: This Phase I study determines the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) for lung tumors. Methods: Eli- gible patients had biopsy proven cancer with a maxi- mum tumor size ≤ 5 cm. Total doses were escalated from 40 to 48, then to 56 Gy, delivered in 4 equal fractions administered 2 to 3 times per week on an IRB approved protocol. SBRT was administered us- ing 5 to 9 fixed beam arrangements with CT loca- lization. Internal target volumes (ITV) were based on breath hold scans or 4D CT simulation. The planning target volume (PTV) was defined as the ITV with a uniform 5 mm expansion. Dose limiting toxicity (DLT) was defined as any grade 3 or higher toxicity using the Radiation Therapy Oncology Group (RTOG) common toxicity criteria (CTC). Results: Between April 2004 and February 2008, 18 patients received the prescribed treatment (40 Gy n = 6, 48 Gy n = 7, 56 Gy n = 5). Seventeen of 18 patients had non-small cell lung cancer (1 with rectal cancer), four of whom were treated for an oligometastasis. The median age of the patients was 68, while the median Karnofsky performance status was 90. The mean tumor size was 2.6 cm (range 0.9 to 4.5 cm). One grade 3 pulmonary event occurred (at 48 Gy dose level) immediately following treatment with the onset of fever and shortness of breath that responded to antibiotics. No other DLTs occurred. Conclusions: SBRT utilizing patient specific target volumes without gating appears safe. The maximum tolerated dose was not reached.
文摘There have been a lot of research exertions and studies to improve the safety of critical infrastructures using the Security Operations Center (SOC). As part of efforts, the purpose of this research is to propose a framework to automate the SOC’s performance of triage, containment and escalation. The research leveraged on qualitative desk review to collect data for analysis, deduced strengths and weaknesses for the current SOC implementations and used that as a basis for proposing the framework. In view of the constant evolution of SOC operations and capabilities coupled with the huge volumes of data collected for analysis, an efficient framework for SOC operations is proposed. The qualitative analysis is used to deduce strengths and weaknesses for the current SOC implementations as a premise for proposing the framework. It consists of eight interactive stages that further leverage on a proposed algorithm for baselining, remediation and escalation. The result of this research is a proposed framework that serves as a unique contribution to enhancing the SOC’s ability to automatically perform triage, containment and escalation. Supplementary to similar and earlier work reviewed, the framework is proposed as the way forward to automatically enable SOC setups with the capacity to efficiently perform triage of security threats, vulnerabilities and incidents, effectively contain identified breaches and appropriately escalate for prompt and accurate solutions.
基金supported by the National Key R&D Program of China(2022YFA1105604,2022YFC2304400)the Innovation Platform for Academicians of Hainan Province(YSPTZX202216)the National Clinical Center for Infectious Diseases,PLA General Hospital(NCRC-ID202105,413FZT6).
文摘Decompensated liver cirrhosis(DLC)is characterized by severe liver dysfunction and immune dysregulation,posing significant treatment challenges.Mesenchymal stromal cell(MSC)therapy has shown promise in DLC treatment,but the optimal dosing strategies and dose-dependent therapeutic mechanisms in humans remain unclear,limiting its clinical application.We conducted sequential Phase Ia/Ib trials using a single-arm,dose-escalation design to evaluate the safety and tolerability of MSC therapy in DLC patients while also exploring its immunomodulatory effects and gathering preliminary therapeutic signals.
文摘In an interview with Beijing Review.Einar Tangen,a senior fellow at the Taihe Institute,a Beijing-based think tank,and a seasoned independent economic commentator,shared his views on what the recent tariff pause between China and U.S.reveals about both sides9 trade strategies,why U.S.tariffs fail to fix trade gaps and whether the 90-day reprieve can lead to lasting solutions.
文摘In the original publication of our paper,“Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia,”published on Blood Science,2024 Jan;6(1):e00179,we have identified several errors that require correction.
文摘Introduction The accuracy of sentinel lymph node biopsy(SLNB)after neoadjuvant therapy(NAT)has been confirmed in clinical nodal stage 1(c N1)patients,and more patients could benefit from axillary surgery de-escalation after NAT(1,2).
基金This study was supported by the Natural Science Foundation of Guangdong Province(2020A1515010105)Joint Fund of the National Natural Science Foundation of China and Natural Science Foundation of Guangdong Province(U1601224).
文摘Background:The introductions of anti-human epidermal growth factor receptor-2(HER2)agents have significantly improved the treatment outcome of patients with HER2-positive breast cancer.BAT8001 is a novel antibodydrug conjugate targeting human epidermal growth factor receptor-2(HER2)-expressing cells composed of a trastuzumab biosimilar linked to the drug-linker Batansine.This dose-escalation,phase I study was designed to assess the safety,tolerability,pharmacokinetics,and preliminary anti-tumor activity of BAT8001 in patients with HER2-positive locally advanced or metastatic breast cancer.Methods:This trial was conducted in subjects with histologically confirmed HER2-positive breast cancer(having evaluable lesions and an Eastern Cooperative Oncology Group performance status of 0 or 1)using a 3+3 design of escalating BAT8001 doses.Patients received BAT8001 intravenously in a 21-day cycle,with dose escalation in 5 cohorts:1.2,2.4,3.6,4.8,and 6.0 mg/kg.The primary objective was to evaluate the safety and tolerability of BAT8001.Preliminary activity of BAT8001 was also assessed as a secondary objective.Results:Between March 2017 to May 2018,29 HER2-positive breast cancer patients were enrolled.The observed dose-limiting toxicities were grade 4 thrombocytopenia and grade 3 elevated transaminase.The maximum tolerated dose was determined to be 3.6 mg/kg.Grade 3 or greater adverse events(AEs)occurred in 14(48.3%)of 29 patients,including thrombocytopenia in 12(41.4%)patients,aspartate aminotransferase increased in 4(13.8%)patients,γ-glutamyl transferase increased in 2(6.9%)patients,alanine aminotransferase increased in 2(6.9%)patients,diarrhea in 2(6.9%)patients.Objective response was observed in 12(41.4%,95%confidence interval[CI]=23.5%-61.1%)and disease control(including patients achieving objective response and stable disease)was observed in 24(82.8%,95%CI=64.2%-94.2%)patients.Conclusions:BAT8001 demonstrated favorable safety profiles,with promising anti-tumor activity in patients with HER2-positive locally advanced or metastatic breast cancer.BAT8001 has the potential to provide a new therapeutic option in patients with metastatic HER2-positive breast cancer.
文摘Objective:To assess the feasibility of dose escalation guided by ^(18)F-deoxyglucose positron emission tomography/computer tomography(^(18)F-FDG PET/CT)for esophageal cancer(EC).Methods and materials:Ten random patients treated with definitive chemoradiotherapy and pre-therapeutic ^(18)FFDG PET/CT were included in this study.Retrospectively,a threshold of 50%of SUVmax was used to define the high FDG uptake region of the GTV(GTVPET).Three intensity-modulated radiation therapy(IMRT)plans were generated,delivering three dose levels to three different planning target volumes(PTVs).50.4 Gy delivered to PTV50.4 was defined on computed tomography(CT)as Plan50.4,63 Gy was delivered to PTV63 was defined as GTV plus a uniform margin of 0.5 cm as Plan63,and 70 Gy delivered to PTV70 was defined as GTVPET plus a 0.5 cm margin as Plan70.A dosimetric comparison was performed based on normal tissue complication probability(NTCP)for the lung and heart.Results:Clinically acceptable dose escalation failed for 2 of 10 patients in Plan63 due to heart dose constraints.One patient failed heart dose constraint for Plan70.Two patients failed spinal cord constraint for Plan63.Three patients failed lung dose constraints for both Plan63 and Plan70,two of which were even not suitable for Plan50.4 for the same reason.NTCP modeling for lung showed increased risk for Plan63 and Plan70 compared to Plan50.4.The difference between Plan63 and Plan70 was insignificant.NTCP modeling for heart showed an increased risk from 6.38%of Plan50.4 to 8.88%of Plan70(P=0.009)or 9.79%of Plan63(P=0.007).The risk of heart mortality was significantly higher for Plan63 than Plan70(P=0.047).Conclusions:Selective boosting of sub-volumes based on ^(18)F-FDG PET/CT is feasible way with a modest increase in the risk of cardiac and lung toxicities.
基金the NERC grant NE/I005803/1 and various colleagues who have been worked in the field to collect the many samples on which our studies are based
文摘We review the evidence for predation of shelly benthic prey over 125 million years of earth history in the James Ross Basin,Antarctica(~65°S).Although poor in the Early Cretaceous lower parts of the sequence,which represent essentially deeper water facies,evidence for both potential crushers and drillers becomes more apparent in the Santonian–Campanian Santa Marta Formation,and by the Maastrichtian López de Bertodano Formation there is an extensive fossil record of drill holes attributable to naticid gastropods,and some evidence of crushing by decapods crustaceans and possibly other taxa too.This continues at a similar level of intensity across the K/Pg boundary into the Danian Sobral Formation,but is less well constrained in the latest Paleocene–Early Eocene.The most extensive record of predation occurs in the Middle Eocene section of the La Meseta Formation on Seymour Island which also records the highest levels of benthic diversity within the entire basin.This key section is providing some important new evidence to suggest that the rate of acceleration of benthic predation intensity through the Late Mesozoic–Early Cenozoic in the polar regions may be similar to that seen in lower latitude regions.Predator–prey interaction was a key factor in the evolution of polar marine faunas too.
文摘Constant escalations in the number of diabetics worldwide and the failure of conventional therapy to restore normoglycemia without adverse effects,in spite of tremendous strides in modern medicine,calls for naturopathy and alternative medicine.Because diabetes is multi-factorial and has secondary complications,prevention of hyperglycemia is the central dogma for its management.To date,no oral hypoglycemic exists which can achieve tight glycemic control without side effects.Dietary adjuncts,lifestyle interventions and a resurgence of interest in phyto-therapy have consequently gained ground.Natural hypoglycemics have attracted attention due to ease of incorporation in everyday diet,affordability,less adverse effects,and long term safety.Ethno botanical literature reports more than 800 anti-diabetic plants species.Eucalyptus is well represented in the Aboriginal Pharmacopoeias for its various pharmacological activities.Its hot aqueous decoction has been used as a hypoglycemic in various regions of world.This editorial attempts to summarize the data on the hypoglycemic potential of the different eucalyptus species,highlight the value of its natural biomolecules for the prophylaxis and treatment of type2 diabetes,describe their mechanistic actions,shed light on the posology and safety aspects of eucalyptusand assess its applicability as a reinforcement to currently used therapy.
文摘Background and Purpose: There have been a number of different efforts trying to improve the outcome of NSCLC patients treated with radiotherapy (RT). Contrary to most expectations, the long awaiting results of the RTOG 0617 trial didn’t show any benefit of dose escalation to 74 Gy. In this unicentric retrospective analysis we compare the RTOG 0617 result with the outcome of our own 74-Gy-NSCLC cohort. Methods and Material: Since October 2009, 80 patients with NSCLC were treated with 74 Gy in 37 fractions, of which 69 patients were eligible for a retrospective analysis of local and distant failure, survival time and treatment related toxicity. A subgroup analysis was done for patients with a possible follow-up of at least 18 month. Results: Complete local remission could be achieved in 18 patients (26.1%);26 patients (37.7%) had a partial remission and 3 patients (4.4%) a stable local disease. Local failure occurred in 12 patients (17.3%). Distant failure occurred in 27 patients (39.1%). The median survival time was 43.7 weeks (95% CI: 25.2 - 62.3 weeks). 5 patients (6.3%) developed RT induced side effects. As for the analyzed subgroup, a complete or partial local remission could be achieved in 29 patients (61.7%). Local failure occurred in 11 patients (23.4%) and 20 patients (42.6%) developed distant metastases. The 18-month overall survival was 38.3% and the median survival time was 51.7 weeks (95% CI: 27.2 - 76.3 weeks). Conclusion: The results of this retrospective analysis indicate that 74 Gy total radiation dose might not lead to results as bad as indicated by the RTOG 0617 trial. It might therefore be a suitable treatment concept for people with NSCLC.
