Comparative effects of different types of exercise on health-related quality of life during and after active cancer treatment:A systematic review and network meta-analysis

Background The positive influence of most types of exercise has been reported repeatedly,but what the most effective exercise approaches are for improving health-related quality of life(HRQoL)in people with cancer remains unknown.The aim of this systematic review and network meta-analysis was to synthesize the evidence from intervention studies to assess the effects of different types of exercise on HRQoL during and after cancer treatment.Methods MEDLINE,SPORTDiscus,the Cochrane Library,Web of Science,and Scopus were searched for randomized controlled trials aimed at testing the effects of exercise interventions meant to improve HRQoL in people with cancer.Separate analyses were conducted for HRQoL as measured by general and cancer-specific questionnaires.We also evaluated whether the effects of exercise were different during and after cancer treatment in both the physical and mental HRQoL domains.Results In total,93 studies involving 7435 people with cancer were included.Network effect size estimates comparing exercise intervention vs.usual care were significant for combined exercise(0.35,95%confidence interval(95%CI):0.14–0.56)for HRQoL as measured by general questionnaires,and for combined(0.31,95%CI:0.13–0.48),mind–body exercise(0.54,95%CI:0.18–0.89),and walking(0.39,95%CI:0.04–0.74)for HRQoL as measured by cancer-specific questionnaires.Conclusion Exercise programs combining aerobic and resistance training can be recommended to improve HRQoL during and after cancer treatment.The scarcity and heterogeneity of these studies prevents us from making recommendations about other exercise modalities due to insufficient evidence.

Neoadjuvant treatment of rectal cancer: Where we are and where we are going

Locally advanced rectal cancer requires a multidisciplinary approach based on total neoadjuvant treatment with radiotherapy(RT)and chemotherapy(ChT),followed by deferred surgery.Currently,alternatives to the standard total neoadjuvant therapy(TNT)are being explored,such as new ChT regimens or the introduction of immunotherapy.With standard TNT,up to a third of patients may achieve a complete pathological response(CPR),potentially avoiding surgery.However,as of now,we lack predictive markers of response that would allow us to define criteria for a conservative organ strategy.The presence of muta-tions,genes,or new imaging tests is helping to define these criteria.An example of this is the diffusion coefficient in the diffusion-weighted sequence of magnetic resonance imaging and the integration of this imaging technique into RT treatment.This allows for the monitoring of the evolution of this coefficient over successive RT sessions,helping to determine which patients will achieve CPR or those who may require intensification of neoadjuvant therapy.

Carbocysteine as Adjuvant Therapy in Acute Respiratory Tract Infections in Patients without Underlying Chronic Conditions: Systematic Review and Meta-Analysis

Objective: This study aims to systematically examine the existing evidence regarding the clinical benefits of carbocysteine as an adjunctive treatment in acute bronchopulmonary and otorhinological processes. Design: Systematic review and meta-analysis. Data sources: An electronic search was conducted across PubMed, Cochrane Library, clinicaltrials.gov, and the European Clinical Trial Register, with the search dated to May 2023. Bibliographic references from other literature reviews and meta-analyses were also reviewed. The search was limited to randomized clinical trials published in any language and year. It was completed by cross-checking the references of the located articles. Methods: Inclusion criteria covered studies assessing systemic or inhaled carbocysteine, regardless of dosing regimen. Concomitant medication use was acceptable if balanced between intervention and control groups. Authors independently extracted data, resolving disagreements through consensus. Methodological quality assessment relied on critical reading of each study. Dichotomous variables were analyzed using odds ratio (OR), and a final effect size was calculated. Statistical significance was established when confidence intervals did not cross the neutral value. Heterogeneity was assessed via the X2 test and I2 index. Results: Out of 318 initially identified studies, 4 met inclusion criteria. The meta-analysis for poor general condition yielded an OR of 0.45 in favor of intervention, p = 0.013, with non-significant heterogeneity. Cough events showed a percentage of 15.8% for carbocysteine vs. 27.2% for placebo. On the seventh day, expectoration rates were 18.37% for carbocysteinevs 33.3% for placebo. Conclusions: The observed clinical benefits align with carbocysteine’s mucoactive and muco-regulatory properties, complemented by anti-inflammatory and antioxidant actions. Carbocysteine stands out among mucolytic agents. In the context of persistent infectious diseases, the study emphasizes the need for further exploration of carbocysteine’s therapeutic potential as an adjunctive treatment for acute respiratory infections. These findings underscore its significance in the evolving landscape of respiratory healthcare.

Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort

BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile.

Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment

BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health outcome.In this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral treatment.AIM To analyze the prevalence/persistence of hepatitis B virus(HBV)preS and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey zone.METHODS Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/mL,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).Serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV mutants.RESULTS High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 preS1 and 5 preS2 deletions).The prevalence of preS deletions was genotype-dependent:3/5(60%)patients with preS2 deletions and 1/2 with preS1 deletions were infected with the HBV-E genotype.Since HBV-E was the most prevalent in sub-Saharan patients,a correlation between preS deletions and ethnicity was also found:6/8(75%)sub-Saharan vs 1/19(5%)Caucasian patients had preS deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-Saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had preS deletions.The HCC related variants were the major strains and persisted over time(up to 48 mo).Patients with preS deletions had a significant higher prevalence of F2 fibrosis stage than the negatives(57%vs 10%,P=0.0078).CONCLUSION HBV genetic analysis of selected populations,like sub-Saharans infected with HBV-E/A genotypes,will allow identification of subpopulations with risk of HCC development due to accumulation of high-risk HBV variants,thus commanding their increased clinical surveillance.

Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers

AIM： To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS： Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pretransplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. RESULTS： After a mean foUow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy （10%） had liver HBV-DNA at 13 mo post-liver transplantation without serum viral markers and did not develop de novo HBV infection.The vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DNA positive in serum and liver, viral DNA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. CONCLUSION： The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the emergence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.

Gastric necrosis: A late complication of nissen fundoplication

Gastric necrosis is a rare condition because of the rich blood supply and the extensive submucosal vascular network of the stomach. "Gas-bloat" syndrome is a well known Nissen fundoplication postoperative complica-tion. It may cause severe gastric dilatation, but very rarely an ischemic compromise of the organ. Other factors, such as gastric outlet obstruction, may concur to cause an intraluminal pressure enough to blockade venous return and ultimately arterial blood supply and oxygen deliver, leading to ischaemia. We report a case of a 63-year-old women, who presented a total gastric necrosis following laparoscopic Nissen fundoplication and a pyloric phytobezoar which was the trigger event. No preexisting gastric motility disorders were present by the time of surgery, as demonstrated in the preop-erative barium swallow, thus a poor mastication(patient needed no dentures) of a high fiber meal(cabbage) may have been predisposing factors for the develop-ment of a bezoar in an otherwise healthy women at the onset of old age. A total gastrectomy with esophagojejunostomy was performed and patient was discharged home after a 7-d hospital stay with no immediate com-plications. We also discuss some technical aspects of the procedure that might be important to reduce the incidence of this complication.

Ultrasound cyclo plasty for the management of glaucoma secondary to ocular irradiation for choroidal melanoma

Dear Editor,In the past, enucleation has been considered the only available option and the standard of care for the management of malignant intraocular tumors. Thanks to the advances in the field of radiotherapy, new therapeutic approaches have been developed in the last decades, such as plaque brachytherapy and proton beam therapy(PBT)^([1]).

Cardiovascular prevention in elderly patients

In recent decades,life expectancy has been increasing significantly.In this scenario,health interventions are ne-cessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiovascular disease.However,the number of elderly patients included in clinical trials is low,thus current clinical practice guidelines do not include specific re-commendations.This document aims to review prevention recommendations focused in patients≥75 years with high or very high cardiovascular risk,regarding objectives,medical treatment options and also including physical exercise and their inclusion in cardiac rehabilitation programs.Also,we will show why geriatric syndromes such as frailty,dependence,cognitive impair-ment,and nutritional status,as well as comorbidities,ought to be considered in this population regarding their important pro-gnostic impact.

The Dallas Donation after Circulatory Death Transplantation Summit:expanding donation after circulatory death procedures through process improvement,broader utilization,and innovation

Despite a significant increase in utilization over the past decade,the number of donation after circulatory death(DCD)organs that are procured and transplanted in the United States(US)remains well below its potential.There is still room for expansion,as utilizing DCD organs to the fullest extent is currently the most viable solution to the persistent mismatch between supply and demand in transplantation.We convened a multidisciplinary transplantation summit to examine various aspects of DCD,with faculty members from around the world with clinical and academic interest in DCD donation and transplantation,including abdominal and cardiothoracic surgeons,organ procurement organization directors,hepatologists,and gastroenterologists.The conference focused on identifying barriers to DCD organ utilization and strategies to overcome these barriers.We divide the barriers to DCD utilization into three mains categories:(Ⅰ)policy and process variation;(II)logistical and transportation challenges;and(Ⅲ)higher risk perceptions related to DCD outcomes.For each barrier,we proposed a variety of solutions,providing an overview of the status of DCD donation in the US and suggestions on how to increase the use of DCD.There is a specific focus on ex situ machine perfusion,normothermic regional perfusion,and other opportunities to expand DCD utilization without negatively impacting recipient outcomes.

Endoscopic management of esophageal varices

The rupture of gastric varices results in variceal hemorrhage, which is one the most lethal complications of cirrhosis. Endoscopic therapies for varices aim to reduce variceal wall tension by obliteration of the varix. The two principal methods available for esophageal varices are endoscopic sclerotherapy (EST) and band ligation (EBL). The advantages of EST are that it is cheap and easy to use, and the injection catheter fits through the working channel of a diagnostic gastroscope. Endoscopic variceal ligation obliterates varices by causing mechanical strangulation with rubber bands. The following review aims to describe the utility of EBL and EST in different situations, such as acute bleeding, primary and secondary

Electrocardiographic changes during induced therapeutic hypothermia in comatose survivors after cardiac arrest

AIM: To assess the safety of therapeutic hypothermia(TH) concerning arrhythmias we analyzed serial electrocardiograms(ECG) during TH.METHODS: All patients recovered from a cardiac arrest with Glasgow < 9 at admission were treated with induced mild TH to 32-34℃. TH was obtained with cool fluid infusion or a specific intravascular device. Twelvelead ECG before,during,and after TH,as well as ECG telemetry data was recorded in all patients. From a total of 54 patients admitted with cardiac arrest during the study period,47 patients had the 3 ECG and telemetry data available. ECG analysis was blinded and performed with manual caliper by two independent cardiologists from blinded copies of original ECG,recorded at 25 mm/s and 10 mm/m V. Coronary care unit staff analyzed ECG telemetry for rhythm disturbances. Variables measured in ECG were rhythm,RR,PR,QT and corrected QT(QTc by Bazett formula,measured in lead v2) intervals,QRS duration,presence of Osborn's J wave and U wave,as well as ST segment displacement and T wave amplitude in leads Ⅱ,v2 and v5.RESULTS: Heart rate went down an average of 19 bpm during hypothermia and increased again 16 bpm with rewarming(P < 0.0005,both). There was a nonsignificant prolongation of the PR interval during TH and a significant decrease with rewarming(P = 0.041). QRS duration significantly prolonged(P = 0.041) with TH and shortened back(P < 0.005) with rewarming. QTc interval presented a mean prolongation of 58 ms(P < 0.005) during TH and a significant shortening with rewarming of 22.2 ms(P = 0.017). Osborn or J wave was found in 21.3% of the patients. New arrhythmias occurred in 38.3% of the patients. Most frequent arrhythmia was non-sustained ventricular tachycardia(19.1%),followed by severe bradycardia or paced rhythm(10.6%),accelerated nodal rhythm(8.5%) and atrial fibrillation(6.4%). No life threatening arrhythmias(sustained ventricular tachycardia,polymorphic ventricular tachycardia or ventricular fibrillation) occurred during TH. CONCLUSION: A 38.3% of patients had cardiac arrhythmias during TH but without life-threatening arrhythmias. A concern may rise when inducing TH to patients with long QT syndrome.

Stem cell therapy in the management of shoulder rotator cuff disorders

Rotator cuff tears are frequent shoulder problems that are usually dealt with surgical repair. Despite improved surgical techniques, the tendon-to-bone healing rate is unsatisfactory due to difficulties in restoring the delicate transitional tissue between bone and tendon. It is essential to understand the molecular mechanisms that determine this failure. The study of the molecular environment during embryogenesis and during normal healing after injury is key in devising strategies to get a successful repair. Mesenchymal stem cells(MSC) can differentiate into different mesodermal tissues and have a strong paracrine, anti-inflammatory, immunoregulatory and angiogenic potential. Stem cell therapy is thus a potentially effective therapy to enhance rotator cuff healing. Promising results have been reported with the use of autologous MSC of different origins in animal studies: they have shown to have better healing properties, increasing the amount of fibrocartilage formation and improving the orientation of fibrocartilage fibers with less immunologic response and reduced lymphocyte infiltration. All these changes lead to an increase in biomechanical strength. However, animal research is still inconclusive and more experimental studies are needed before human application. Future directions include expanded stem cell therapy in combination with growth factors or different scaffolds as well as new stem cell types and gene therapy.

Presence of c.3956del C mutation in familial adenomatous polyposis patients from Brazil

AIM: To characterize APC gene mutations and correlate them with patient phenotypes in individuals diagnosed with familial adenomatous polyposis(FAP) in northern Brazil. METHODS: A total of 15 individuals diagnosed with FAP from 5 different families from the north of Brazil were analyzed in this study. In addition to patients with histopathological diagnosis of FAP,family members who had not developed the disease were also tested in order to identify mutations and for possible genetic counseling. All analyzed patients or their guardians signed a consent form approved by the Research Ethics Committee of the Jo?o de Barros Barreto University Hospital(Belem,Brazil). DNA extracted from the peripheral blood of a member of each of the affected families was subjected to direct sequencing. The proband of each family was sequenced to identify germline mutations using the Ion Torrent platform. To validate the detected mutations,Sanger sequencing was also performed. The samples from all patients were also tested for the identification of mutations by real-time quantitative polymerase chain reaction using the amplification refractory mutation system. RESULTS: Through interviews with relatives and a search of medical records,it was possible to construct genograms for three of the five families included in the study. All 15 patients from the five families with FAP exhibited mutations in the APC gene,and all mutations were detected in exon 15 of the APC gene. In addition to the patients with a histological diagnosis of FAP,family members without disease symptoms showed the mutation in the APC gene. In the present study,we detected two of the three most frequent germline mutations in the literature: the mutation at codon 1309 and the mutation at codon 1061. The presence of c.3956 del C mutation was found in all families from this study,and suggests that this mutation was introduced in the population of the State of Pará through ancestor immigration(i.e.,a de novo mutation that arose in one member belonging to this state from Brazil). CONCLUSION: Regardless of its origin,the c.3956 del C mutation is a strong candidate biomarker of this hereditary cancer syndrome in families of northern Brazil.

Healthcare staff as promoters of parental presence at anesthetic induction:Net Promoter Score survey

BACKGROUND Surgical intervention is usually a traumatic event that causes stress and anxiety in the pediatric patient and the family environment.To reduce the harmful effects of presurgical anxiety,parental presence during induction of anesthesia(PPIA)is one of the more notable interventions used in medical centers.However,data on this measure are difficult to evaluate and often face resistance from healthcare staff.AIM To analyze the perception of the healthcare workers after the implementation of a PPIA program.METHODS A survey was developed and sent by email to all the healthcare staff working in the children’s area of a tertiary hospital.It consisted of 14 items divided into positive aspects of PPIA and negative aspects of PPIA evaluated with the use of a Likert scale(1 to 5).The demographics of the respondents were included in the data collected.The answers to the questions were interpreted through the Net Promoter Score(NPS).The statistical analysis compared the differences in the responses to each question of the survey made by the different groups of health personnel included.RESULTS A total of 141 surveys were sent out,with a response rate of 69%.Of the total number of responses,68%were from women and 32%from men.The average age of the participants was 42.3±10.6 years.As for the positive questions about the PPIA,83%had an NPS>50,and only one had a score between 0 and 50,which means that the quality of the service was rated as excellent or good by 100%of the respondents.On the other hand,100%of the negative questions about the PPIA had a negative NPS.Responses to the question“PPIA increases patient safety”were significantly different(P=0.037),with a lower percentage of pediatric surgeons(70%)thinking that PPIA increased patient safety,compared with anesthesiologists(90%),nursing(92%),and other medical personnel(96%).CONCLUSION The personnel who participated in the PPIA program at our center were in favor of implementation.There were no validated arguments to support worker resistance to the development of the PPIA.

选择性骨盆动脉栓塞术治疗产科出血

Objective: Retrospective evaluation of pelvic arterial embolization for the treatment of severe post-partum hemorrhage. Methods: Data were collected, from our departmental clinical records, on all patients with life-threatening post-partum hemorrhage managed with arterial embolization between January 2001 and December 2003. Results: During the period analyzed, there were 29,119 deliveries in our institution. Of these, 27 patients underwent pelvic arterial embolization to control severe hemorrhaging despite conservative management. Of the 27 patients, 22(81.5%) had a vaginal delivery and 5 had a caesarean section. The major indication for embolization was uterine atony(15 women). Disseminated intravascular coagulation developed in 20 cases(74.1%). There were eight cases(29.6%) who underwent hysterectomy, seven of them pre-emboliza-tion. The most frequent vessel embolized was the uterine artery(13 cases; 38.3%). One patient(3.7%) presented complications related to the procedure. The success rate was 96.3%. Conclusion: Pelvic arterial embolization is a good therapeutic choice for severe post-partum hemorrhage refractory to conservative treatment measures.

Management of betablocked patients after sustained virological response in hepatitis C cirrhosis

BACKGROUND Current guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option. AIM To assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population. METHODS Inclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after directacting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician. RESULTS Sample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/μL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography area under receiver operating characteristic for HVPG ≥ 12 mmHg was 0.62. Betablockers were stopped permanently in 10/13 patients with gradient < 12 mmHg, with no bleeding episodes after a median follow-up of 68 wk. CONCLUSION Portal hypertension dropped below the bleeding threshold in 39% of patients more than one year after antiviral treatment. Endoscopy and transient elastography are inaccurate for reliable detection of this change. Stopping betablockers permanently seems uneventful in patients with a gradient < 12 mmHg.

Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

AIM: To study the hepatitis B virus(HBV) and hepatitis D virus(HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV genotypes.METHODS: We conducted a transversal study including 68 chronic hepatitis delta(CHD)(37 HIVpositive) patients and a control group of 49 chronic hepatitis B(CHB)(22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B(HBs Ag) serum titers were analyzed with the Monolisa HBs Ag Ultra system(Bio-Rad), using as quantification standard a serial dilution curve of an international HBs Ag standard. Serum HBV-DNA titers were analyzed using the Roche Cobas Taq Man(Roche, Barcelona, Spain), and the serum HDV-RNA using an in-house real-time q RT-PCR method, with Taq Man probes. HBV genotype was determined with the line immunoassay Li PA HBV genotyping system(Innogenetics, Ghent, Belgium). In those patients negative for Li PA assay, a nested PCR method of complete HBs Ag coding region, followed by sequence analysis was applied.RESULTS: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median(IQR): 1.25(1.00-1.35) vs 2.95(2.07-3.93) log10(copies/m L), P = 0.013] and HIV positive patients [2.63(1.24-2.69) vs 7.25(4.61-7.55) log10(copies/m L), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with Li PA assay. Finally, the HBs Ag titers reflected no significant differences in CHD patients infected with HBV-A or D.CONCLUSION: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E.

New frontiers in focal therapy for prostate cancer:Prostate-specific membrane antigen positron emission tomography/magnetic resonance imaging

Imaging has a central role in the context of focal therapy(FT)for prostate cancer(PCa).Prostate-specific membrane antigen(PSMA)positron emission tomography/magnetic resonance imaging(PET/MRI)is a novel imaging modality that combines the morpho-functional information of MRI with the molecular characterization of PET.Some papers reported the potential advantages of PSMA PET/MRI in different clinical scenarios.Limited evidence on PSMA PET/MRI is available in the setting of FT.PSMA PET/MRI can be an effective imaging modality for detecting primary PCa and seems to provide accurate local staging of primary PCa.PSMA PET/MRI also shows high performance for restaging and detecting tumor recurrence.The higher soft-tissue contrast and the reduction of ionizing radiation are the main advantages reported in the literature compared to PET/computed tomography.PSMA PET/MRI could represent a turning point in the management of patients with PCa in the context of FT.Further studies are needed to confirm its applications in this specific clinical setting.

Immunotherapy combinations and chemotherapy sparing schemes in first line non-small cell lung cancer

In recent years,studies have explored different combinations of immunotherapy and chemotherapy.The rationale behind these is the improved survival outcomes of new immunologic therapies used in first-line-treatment of advanced non-small cell lung cancer.Moreover,for the most-studied combinations of anti-programed death-1(PD-1)/programed death ligand-1(PD-L1)with the addition of platinumbased chemotherapy,recent research is investigating whether combining different immunologic antitumoral mechanisms of action,such as anti-PD-1/PD-L1 and anti-CTLA-4,or anti-PD-L1 and anti-TIGIT,with or without chemotherapy,can improve efficacy outcomes compared with more classical combinations,or compared with standard chemotherapy alone.Here,we present the data of the main randomized studies that have evaluated these combinations,focusing on the basic rationale behind the different combinations,and the efficacy and tolerability data available to date.