Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease

AIM: To establish the efficacy and safety of a 7-d therapeutic regimen using omeprazole,bismuth subcitrate,furazolidone and amoxicillin in patients with peptic ulcer disease who had been previously treated with other therapeutic regimens without success.METHODS: Open cohort study which included patients with peptic ulcer who had previously been treated unsuccessfully with one or more eradication regimens.The therapeutic regimen consisted of 20 mg omeprazole,240 mg colloidal bismuth subcitrate,1000 mg amoxicillin,and 200 mg furazolidone,taken twice a day for 7 d.Patients were considered as eradicated when samples taken from the gastric antrum and corpus 12 wk after the end of treatment were negative for Helicobacter pylori (H pylori) (rapid urease test and histology).Safety was determined by the presence of adverse effects.RESULTS: Fifty-one patients were enrolled.The eradication rate was 68.8% (31/45).Adverse effects were reported by 31.4% of the patients,and these were usually considered to be slight or moderate in the majority of the cases.Three patients had to withdraw from the treatment due to the presence of severe adverse effects.CONCLUSION: The association of bismuth,furazolidone,amoxicillin and a proton-pump inhibitor is a valuable alternative for patients who failed to respond to other eradication regimens.It is an effective,cheap and safe option for salvage therapy of positive patients.

Follow-up Study of Retreatment TB Patients with Sputum Smear and/or Culture Positive Two Years after They were Declared Cured with First-line Anti-TB Drugs in Shandong Province

This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive （ss＋ and/or c＋） two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination.

Heterogeneity of immune control in chronic hepatitis B virus infection:Clinical implications on immunity with interferon-αtreatment and retreatment

Hepatitis B virus(HBV)infection is a global public health issue.Interferon-α(IFN-α)treatment has been used to treat hepatitis B for over 20 years,but fewer than 5%of Asians receiving IFN-αtreatment achieve functional cure.Thus,IFN-αretreatment has been introduced to enhance antiviral function.In recent years,immune-related studies have found that the complex interactions between immune cells and cytokines could modulate immune response networks,including both innate and adaptive immunity,triggering immune responses that control HBV replication.However,heterogeneity of the immune system to control HBV infection,particularly HBV-specific CD8^(+)T cell heterogeneity,has consequential effects on T cell-based immunotherapy for treating HBV infection.Altogether,the host’s genetic variants,negative-feedback regulators and HBV components affecting the immune system's ability to control HBV.In this study,we reviewed the literature on potential immune mechanisms affecting the immune control of HBV and the clinical effects of IFN-αtreatment and retreatment.

Impact of ribavirin dose on retreatment of chronic hepatitis C patients

AIM: To study the efficacy and factors associated with a sustained virological response (SVR) in chronic hepatitis C (CHC) relapsing patients. METHODS: Out of 1228 CHC patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV), 165 (13%) had a relapse. Among these, 62 patients were retreated with PEG-IFN-2a or-2b and RBV. Clinical, biological, virological and histological data were collected. Initial doses and treatment modifications were recorded. The efficacy of retreatment and predictive factors for SVR were analyzed. RESULTS: An SVR was achieved in 42% of patients. SVR was higher in young (< 50 years) (61%) than old patients (27%) (P = 0.007), and in genotype 2 or 3 (57%) than in genotype 1 or 4 (28%) patients (P = 0.023). Prolonging therapy for at least 24 wk more than the previous course was associated with higher SVR rates (53% vs 28%, P = 0.04). Also, a better SVR rate was observed with RBV dose/body weight > 15.2 mg/kg per day (70% vs 35%, P = 0.04). In logistic regression, predictors of a response were age (P = 0.018), genotype (P = 0.048) and initial RBV dose/body weight (P = 0.022). None of the patients without a complete early virological response achieved an SVR (negative predictive value = 100%). CONCLUSION: Retreatment with PEG-IFN/RBV is effective in genotype 2 or 3 relapsers, especially in young patients. A high dose of RBV seems to be important for the retreatment response.

Assessment of Retreatment Tuberculosis Cases amongst All Tuberculosis Cases Notification in District Swat 2015-2017: A Retrospective Cohort Review

Retreatment Tuberculosis (TB) has long been a neglected area in global TB control. To determine the notification of re-treatment Tuberculosis TB cases among all enrolled TB patients, we conducted a retrospective cohort review of routine program data from 2015-2017. A total of 8663 tuberculosis cases (all new and old forms) were registered at the study site. Of these, 1916 (22%) were pulmonary bacteriological confirmed;3498 (40.37%) were pulmonary clinical diagnosed and 3396 (39.20%) were clinically or bacteriological confirmed extra-pulmonary tuberculosis cases. Retreatment cases trend was found to be increased from 1% in 2015 to 1.6% in 2017. Majority of re-treatment cases were in the age group 18 - 43 years and only 7 patients were under the age of 15 years. This concludes that notification of re-treatment cases is very low among all enrolled TB patients and this could be possibly due to the fact that most of the re-treatment cases were registered as new cases or misdiagnosed. There is need and space to increase retreatment cases. Most of the re-treatment cases were usually converted to MDR-TB (Multi-Drug Resistant Tuberculosis) as noted in PMDT (Programmatic management of Drugs resistant tuberculosis) site. Therefore, proper history and diagnosis should be encouraged at the time of case notification.

Spectrum of Filamentous Fungi from Sputum of Tuberculosis Relapse and Retreatment Patients in Tuberculosis Reference Facilities

Background: Fungal infections represent a significant cause of morbidity and mortality among immunocompromised individuals. Pulmonary fungal infection may be missed or misdiagnosed as tuberculosis (TB) hence complicating management of these patients. The current study reports the spectrum of filamentous fungi isolated from sputum of TB relapse and retreatment cases at selected reference facilities in Kenya. Methods: A total of 340 sputum samples collected during the period of June 2018 to June 2019 were subjected to mycological investigations. The samples were mucolysed and inoculated on sabourauds dextrose agar (SDA) and incubated at 30°C for 7 days and checked daily for fungal growth. Moulds were identified by macroscopic and microscopic morphological features and the species were confirmed by sequencing. Results: The diversity of fungi out of the 340 sputum samples analyzed was as follows;16% (n = 53) were positive for moulds with Aspergillus species being the predominant constituting 68 % (n = 36). Among the Aspergilli, A. flavus and A. niger were the most frequently isolated adding up to 23%, (n = 12) and 15% (n = 8) respectively. Additionally, Paecillomyces variotii (9%, n = 5), Scedosporium aspiospermum (6%, n = 3), Mucor racemosus (8%, n = 4) and Penicillium spp. (9%, n = 5) were also recovered. Conclusion: The isolated fungi represented potential respiratory pathogens that could be responsible for persistent TB like symptoms despite treatment that could be misdiagnosed as relapse requiring treatment. Fungal investigation of all presumptive TB relapse cases should be advocated before treatment. This will reduce unnecessary retreatment, delayed antifungal intervention and unwarranted morbidity and mortality associated with misdiagnosis.

Non-Surgical Endodontic Retreatment of Anterior Tooth with a Large Periapical Lesion and Extruded Guta Percha with 36 Months Follow-Up: A Case Report

Root canal treatment failure depends on many factors. Overfillings, insufficient fillings, missing canals, failure to provide a complete apical plug, and impermeability of coronal restoration are some of them. Failed root canal treatment may not always manifest itself immediately after treatment. Sometimes, root canal treatments, which have not been done well, can manifest themselves with extensive lesions and severe pain in the apical after a long time. Apical resection may be considered as a solution in lesions that are too large to be treated, but retreatment without surgery should be attempted beforehand. Thus, the patient may have recovered from unnecessary surgical procedures and treated with a more conservative method. This case presents the non-surgical retreatment of a left lateral tooth with a large periapical lesion with extruded gutta percha followed by a 36-month follow-up.

Enhanced Biohydrogen Production by Accelerating the Hydrolysis of Macromolecular Components of Waste Activated Sludge Using TiO₂Photocatalysis as a Pretreatment

The effects of TiO2 photocatalysis on the hydrolysis of protein of waste activated sludge (WAS) and its biodegradability were investigated in this study. After 12-h UV irradiation, the removal ratio of protein by TiO2 photocatalysis reached 98.1%. The optimal condition for photocatalytic degradation of protein is TiO2 dosage of 5.0 mg·L–1 under 2.4 w·m–2 UV light irradiation. TiO2 photocatalysis in comparison with other pretreatments obviously accelerated the hydrolysis of WAS and improved the conversion of total COD (tCOD) to soluble COD (sCOD). The sCOD/tCOD ratio of WAS pretreated by TiO2 photocatalysis, UV photolysis and TiO2 adsorption and that of the control were 92.8%, 32.5%, 18.0% and 16.6%, respectively. TiO2 photocatalytic pretreatment accelerated the biohydrogen production from 10-fold diluted WAS. The bioreactors containing UV photolysis and TiO2 adsorption pretreated WASs and the control reactor require 0.5-d, 0.9-d and 0.7-d start-up period for biohydrogen production, respectively. While the bioreactor containing TiO2 photocatalysis pretreated WAS obtained a hydrogen yield of 0.5 mL-H2/g-VS merely after 0.5-d mesophilic fermentation. The cumulative biohydrogen production from TiO2 photocatalysis pretreated WAS during 4-d mesophilic fermentation reached 11.7 mL-H2/g-VS, which was 1.2 times higher than that from the control. TiO2 photocatalytic pretreatment enhanced the biohydrogen production from WAS via accelerating the hydrolysis of its macromolecular components to smaller molecule weight hydrolysates.

Improvement cues of lesion absorption using the adjuvant therapy of traditional Chinese medicine Qinbudan tablet for retreatment pulmonary tuberculosis with standard anti-tuberculosis regimen

Background:China is the second highest pulmonary tuberculosis(PTB)burden country worldwide.However,retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs.The cure rate(approximately 50.0–73.3%)and management of retreatment of PTB in China needs to be improved.Qinbudan decoction has been widely used to treat PTB in China since the 1960s.Previously clinical studies have shown that the Qinbudan tablet(QBDT)promoted sputum-culture negative conversion and lesion absorption.However,powerful evidence from a randomized controlled clinical trial is lacking.Therefore,the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB.Methods:We conducted a multicenter,randomized,double-blind,placebo-controlled clinical trial in China.People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013.The treatment group received an anti-TB regimen and QBDT,and the control group was administered an anti-TB regimen plus placebo.Anti-TB treatment options included isoniazid,rifampicin,pyrazinamide,ethambutol,streptomycin for 2 months(2HRZES),followed by isoniazid,rifampicin,ethambutol for 6 months(6HRE),daily for 8 months.Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method.Secondary outcomes included lung lesion absorption and cavity closure.Adverse events and reactions were observed after treatment.A structured questionnaire was used to record demographic information and clinical symptoms of all subjects.Data analysis was performed by SPSS 25.0 software in the full analysis set(FAS)population.Results:One hundred eighty-one cases of retreatment PTB were randomly divided into two groups:the placebo group(88 cases)and the QBDT group(93 cases).A total of 166 patients completed the trial and 15 patients lost to follow-up.The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences(79.6%vs 69.3%;rate difference=0.10,95%confidence interval(CI):-0.02–0.23;F=2.48,P=0.12)after treatment.A significant 16.6%increase in lesion absorption was observed in the QBDT group when compared with the placebo group(67.7%vs 51.1%;rate difference=0.17,95%CI:0.02–0.31;χ2=5.56,P=0.02).The intervention and placebo group did not differ in terms of cavity closure(25.5%vs 21.1%;rate difference=0.04,95%CI:-0.21–0.12;χ2=0.27,P=0.60).Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting.Conclusions:No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen.However,QBDT as an adjunct therapy significantly promoted lesion absorption,thereby reducing lung injury due to Mycobacterium tuberculosis infection.Trial registration:This trial is registered at ClinicalTrials.gov,NCT02313610.

Wavefront-optimized surface retreatments of refractive error following previous laser refractive surgery: a retrospective study

Background:Retreatments are sometimes necessary to correct residual or induced refractive errors following refractive surgery.Many different combinations of primary treatment methods and retreatment techniques have been studied,however,few studies have investigated wavefront-optimized(WFO)technology for retreatment following primary refractive surgery.This study aimed to report the outcomes of WFO photorefractive keratectomy(PRK)retreatments of refractive error following previous laser refractive surgery with PRK,laser in situ keratomileusis(LASIK),or laser-assisted subepithelial keratectomy(LASEK).Methods:We reviewed records of patients who underwent WFO PRK retreatments using the Allegretto Wave Eye-Q 400 Hz Excimer Laser System(Alcon Surgical)between January 2008 and April 2011 at Walter Reed Army Medical Center and Madigan Army Medical Center.Outcomes were recorded in terms of uncorrected distance visual acuity(UDVA),manifest refraction spherical equivalent(MRSE),corrected distance visual acuity(CDVA),and complications at 1 month(M),3 M,and 6 M post-op.Results:Seventy-eight patients(120 eyes)underwent WFO PRK retreatment during the study period.Primary surgery was surface ablation in 87 eyes(78 PRK,9 LASEK)and LASIK in 33 eyes.The mean spherical equivalent before retreatment was−0.79±0.94 D(−3.00 to 1.88 D).UDVA was≥20/20 in 69 eyes(60.0%)at 1 M,54 eyes(71.1%)at 3 M,and 27 eyes(73.0%)at 6 M follow-up.MRSE was within±0.50 D of emmetropia in 78 eyes(67.8%)at 1 M,59 eyes(77.6%)at 3 M,and 25 eyes(67.6%)at 6 M follow-up.CDVA was maintained within±1 line of pre-op in 113 of 115 eyes(98.3%)at 1 M,74 of 76 eyes(97.4%)at 3 M,and 37 eyes(100%)at 6 M follow-up.Conclusion:Although follow-up was limited beyond 3 M,WFO PRK retreatments in patients with residual refractive error may be a safe and effective procedure.Further studies are necessary to determine the long-term safety and stability of outcomes.

Glacial lakes under climate change: the imperative for comparative studies of microbial carbon metabolism in the Qinghai-Xizang Plateau and the Arctic

Glacial lakes,intimately linked to glacier termini,are crucial landscape features of the Qinghai-Xizang Plateau(QXP,Qinghai-Tibet Plateau)and the Arctic.Climate warming has accelerated glacier retreat and the rapid expansion of glacial lakes in both regions.Despite being typically considered harsh environments,these lakes serve as vital reservoirs for microbial biodiversity and carbon metabolism.In the face of climate change,glacial lake ecosystems over the QXP and the Arctic are undergoing unprecedentedtransformations.Thisopinioneditorial highlights the significance of conducting research and establishing long-term monitoring programs focused on microbial carbon metabolism in these glacial lakes.

Bedrock outcropping in the accumulation zone of the largest glacier in Mexico(Glaciar Norte of Citlaltépetl),as evidence of a possible accelerated extinction

The highest volcano in Mexico,at the same time the third largest mountain in North America(Citlaltépetl,5610 m a.s.l.),is home to the largest glacier in the country.Because of the extinction of the Popocatépetl glacier(5500 m a.s.l.)caused by eruptive activity,and the almost disappearance of the Iztaccíhuatl glaciers(5220 m a.s.l.)due to the lower elevation of the mountain,the Glaciar Norte of Citlatépetl has been the only glacier that has shown a certain degree of stability as a response to the altitude in which it is located.However,as occurs in almost all glaciers on the planet,the retreat of its glacier terminus has been continuous.Furthermore,during the last years the thickness of its upper part began to decrease rapidly until its bedrock was exposed for the first time in 2019.Due to its ecosystem importance and because it is the main glacier in Mexico,as well as the only one in the world located at latitude 19°N,in this work its current dimensions are updated,as well as the local climatology that governs the current state of the glacier is pointed out.The study was based on the analysis of high-resolution Sentinel-2 optical images,as well as through Sentinel-1 SAR images,with the support of climatological information from the study area.Therefore,the outcropping of the bedrock in the accumulation zone and the consequent horizontal retreat of the upper part of the glacier are documented;at the same time,the decrease in the thickness of the ice along it is noted.The rocky outcrop in the accumulation zone suggests that the flow dynamics of the ice towards the ablation zone will be considerably less,accelerating the retreat of the glacier terminus.Finally,the ascent of the glacial front to 5102 m a.s.l.and the modelled altitude of the equilibrium line to 5276 m a.s.l.are reported as a warning signal in terms of snow catchment and mass balance;likewise,the decrease of 23%of its surface is also indicated regarding the surface reduction monitoring that has been done until 2017.These findings may indicate that the future of this glacier is related to its possible extinction sooner than previously thought,with severe environmental consequences,especially in terms of the provision of drinking water for thousands of inhabitants of the slopes of the volcano.This research is expected to help reflect on the impacts of current climate variability and at the same time serve as a reference for the tropical glaciers on the planet.

Fenofibrate for patients with asymptomatic primary biliary cirrhosis

AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation.However, only 20-30% of patients respond fully to UDCA.Recently,lipoprotein-lowering agents have been found to be effective for PBC.The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor α,in patients with aPBC.METHODS:Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA.UDCA was used along with fenofibrate during the study.The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study.RESULTS: The serum levels of alkaline phosphatase (ALP)(285±114.8IU/L) and immunoglobulin M (IgM) (255.8±85.9mg/dl) significantly decreased to 186.9±76.2IU/L and 192.9±67.5mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover,the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients.CONCLUSION:Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone.Although the mechanism of fenofibrate on aPBC has not yet been fully clarified,combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its antiinflammatory effect.

Efficacy of ultrasonography and alpha-fetoprotein on early detection of hepatocellular carcinoma

AIM： To evaluate the effectiveness of ultrasonographic screening for early detection of hepatocellular carcinoma （HCC）. METHODS： The data of 14 968 patients who had ultrasonography （US） for chronic liver diseases were collected into a database program from June 1995 to June 2005. The risk factors for HCC were also studied. A total of 6089 patients who had repeated US were enrolled, 264 patients were diagnosed with HCC during follow-up （mean, 39 mo）. RESULTS： The detection rate of small HCC （≤ 3 cm in diameter） was 67.7%. The tumor size detected by screening at the intervals of 6 mo was significantly smaller than that at longer intervals. Only 29.3% of HCC patients had an elevated serum alpha fetoprotein （AFP） level above 400 ng/mL. The risk of HCC development during follow-up was higher in patients with liver cirrhosis （10.9%） and hepatitis C （9.0%） than in patients with chronic hepatitis （4.2%）, hepatitis B （4.9%） and non-B, non-C hepatitis （NBNC, 3.9%）. CONCLUSION： US screening at a interval of 6 mo is beneficial to high-risk patients over 40 years old and the early detection of HCC prolongs survival.

Three-dimensional inlay-guided endodontics applied in variant root canals: A case report and review of literature

BACKGROUND Root canal retreatment is common after root canal therapy in clinical situations.Especially,completing the retreatment of variant root canals can be challenging.This is particularly true for the molars located at the end of the dental arch.However,advancements in digital dental diagnosis and treatment techniques can solve these problems.Here,we describe a case of a maxillary second molar with a variant distobuccal root canal treated via a novel“inlay-guided endodontics”technique based on improved computer-generated programs.CASE SUMMARY A 63-year-old man complained of a defect in the maxillary left second molar.The tooth,diagnosed with post-treatment endodontic disease,was initially treated by conventional methods,which were ineffective.Our“inlay-guided endodontics”technique was subsequently adopted,with the establishment of a precise integrated three-dimensional(3D)plate model of cone-beam computed tomography data and a digital impression of the dentition.An optimal root canal approach was generated for the“virtual file”in the 3D model.The plate data were imported into a 3D printer and printed.With the help of the guide plate,the file was accurately placed into the cervical third of the distal root canal.The root canal and prosthodontic treatments successfully proceeded subsequently.CONCLUSION Our newly developed inlay guide plates may facilitate individualized and minimally invasive root canal treatment.

Target Z-axis Optimized LASIK for 2 Cases with Decentered Ablation

Purpose: To report target z-axis optimized LASIK treating for two eyes from two patients with decentered ablation. Methods: The LaserSight AstraPro2.2 Z software is a topography-guided custom ellipsoid ablation platform. LASIK with target z-axis optimization was performed to restore pre-operative visual axis using a LaserSight SLX excimer laser (version 5.3,300 Hz). Results: During preoperative examination, the uncorrected visual acuity (UCVA) was 0.5 in both eyes, and the best spectacle-corrected visual acuity(BSCVA) was 1.0 and 0.8. The decentered ablation zones were diagnosed with LaserSight AstraMax topography. Following target z-axis microtranslation, fifteen and eight μm of central corneal tissues were preserved in the two eyes respectively,the UCVA was 1.2 in both eyes, and secondary ablation zones were both centered on the visual axis.Topography maps and UCVA were stable in both eyes at the time of final follow-up. Conclusions: Using target z-axis optimized LASIK with the LaserSight AstraPro Planner 2.2 Z customized ablation software was an effective method to modify decentered ablation and restore the visual axis.

Comparative Study on the Effectiveness of Two Nickel-titanium Instruments in Removing Gutta-percha

[Objectives]This study is to investigate the difference in the comprehensive effects of the two types of machine-used nickel-titanium(ni-ti)instruments in removing root canal filling materials to provide guidance for clinical applications.[Methods]We selected 60 single-tube premolars and randomly divided them into a P group(ProTaper ni-ti file group)and a K group(K3 ni-ti file group).The root canal was prepared according to the uniform standard crown cutting and manual k-file stepwise regression method.The root canal was fully filled and the X-ray film was taken.X-rays were taken again after re-treatment.The removal rate of the root filler material was obtained using Auto CAD 2000 image analysis software.[Results]We found no statistical difference in the clearance and total time of the two nickel-titanium devices in removing the gum filling material.Both the ProTaper ni-ti file and the K3 ni-ti file were able to remove most of the root canal filling during root canal retreatment.[Conclusions]There was no significant difference between the two devices in clinical applications.

Triple administration of osimertinib followed by chemotherapy for advanced lung adenocarcinoma: A case report

BACKGROUND Osimertinib is the recommended first-line treatment for adult patients with epidermal growth factor receptor(EGFR)mutation positive advanced or metastatic non-small cell lung cancer(NSCLC).However,primary or acquired resistance to EGFR-tyrosine kinase inhibitors(EGFR-TKIs)seems inevitable,and when drug-resistance occurs during treatment with osimertinib,the standard of care is to discontinue the TKI.CASE SUMMARY A 57-year-old female patient with lung adenocarcinoma presented with an irritating cough accompanied by chest distress of one month duration.An enhanced head magnetic resonance imaging scan showed brain metastases.An EGFR mutation(exon 21 L858R)was detected in pleural fluid.The patient was treated with oral osimertinib(80 mg once daily)from January 2018 but developed progressive disease on December 2018.She was then successfully treated with rechallenge and tri-challenge with osimertinib(80 mg once daily)by resensitization chemotherapy twice after the occurrence of drug-resistance to osimertinib,and to date has survived for 31 mo.CONCLUSION This case may provide some selective therapeutic options for NSCLC patients with acquired drug-resistance who were previously controlled on osimertinib treatment.

Discontinuation of antiviral therapy in chronic hepatitis B patients

Nucleos(t)ide analogs(NUC)are the first-line therapy for patients with chronic hepatitis B(CHB)recommended by most current guidelines.NUC therapy decreases progression of liver disease,reduces the risk of liver-related complications,and improves the quality of life of patients with CHB.Although indefinite or long-term NUC therapy is usually recommended,this strategy raises several concerns,such as side-effects,adherence,costs,and patient willingness to stop therapy.Recent data showed the feasibility,efficacy,and safety of stopping antiviral therapy in carefully selected CHB patients,leading to its incorporation in international guidelines.Patients who discontinue NUC have a higher likelihood of hepatitis B surface antigen(HBsAg)loss compared to patients who continue on therapy.Recommendations pertaining endpoints allowing safety discontinuation of NUC therapy differ among international guidelines.For hepatitis B e antigen(HBeAg)-positive patients,durable HBeAg seroconversion is considered an acceptable treatment endpoint.For HBeAg-negative patients,some guidelines propose undetectability hepatitis B virus DNA for at least 2 or 3 years,while others consider HBsAg loss as the only acceptable endpoint.CHB patients who stop therapy should remain under strict clinical and laboratorial follow-up protocols to detect and manage relapses in a timely manner.No reliable predictor of relapse has been consistently identified to date,although quantitative HBsAg has been increasingly studied as a reliable biomarker to predict safe NUC discontinuation.

Challenges in the discontinuation of chronic hepatitis B antiviral agents

Long-term antiviral treatment of chronic hepatitis B patients has been proven to be beneficial in reducing liver-related complications.However,lengthy periods of daily administration of medication have some inevitable drawbacks,including decreased medication adherence,increased cost of treatment,and possible longterm side effects.Currently,discontinuation of antiviral agent has become the strategy of interest to many hepatologists,as it might alleviate the aforementioned drawbacks and increase the probability of achieving functional cure.This review focuses on the current evidence of the outcomes following stopping antiviral treatment and the factors associated with subsequent hepatitis B virus relapse,hepatitis B surface antigen clearance,and unmet needs.