[Mobile health in primary care. New challenges in the development of solutions to promote physical activity and well-being]. / La salud móvil en atención primaria. Nuevos desafíos en el desarrollo de soluciones para promover la actividad física y el bienestar.

The use of smart devices such as mobile phones (smartphones) or smart watches (smartwatch) to promote physical activity and well-being has increased in recent years among patients and professionals in primary care. This change is driven by the access of patients and professionals to a large catalog of health applications, which can complement the provision of services and promote the empowerment of patients in their own health and lifestyles. These applications are beginning to be integrated with areas such as Artificial Intelligence (AI), the Internet of Medical Things (IoMT) and data storage in the cloud, among other emerging technological systems, offering a new complementary approach to clinical practice known so far. Despite the great potential, there are numerous limitations and major challenges for its full implementation in clinical practice.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists.

BACKGROUND & AIMS: Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. METHODS: We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. RESULTS: The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). CONCLUSION: In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

DNase Treatment Prevents Cerebrospinal Fluid Block in Early Experimental Pneumococcal Meningitis.

OBJECTIVE: Streptococcus pneumoniae is the most common cause of bacterial meningitis, a disease that, despite treatment with antibiotics, still is associated with high mortality and morbidity worldwide. Diffuse brain swelling is a leading cause of morbidity in S pneumoniae meningitis. We hypothesized that neutrophil extracellular traps (NETs) disrupt cerebrospinal fluid (CSF) transport by the glymphatic system and contribute to edema formation in S pneumoniae meningitis. METHODS: We used DNase I treatment to disrupt NETs and then assessed glymphatic function by cisterna magna injections of CSF tracers in a rat model of S pneumoniae meningitis. RESULTS: Our analysis showed that CSF influx into the brain parenchyma, as well as CSF drainage to the cervical lymph nodes, was significantly reduced in the rat model of S pneumoniae meningitis. Degrading NETs by DNase treatment restored glymphatic transport and eliminated the increase in brain weight in the rats. In contrast, first-line antibiotic treatment had no such effect on restoring fluid dynamics. INTERPRETATION: This study suggests that CSF accumulation is responsible for cerebral edema formation and identifies the glymphatic system and NETs as possible new treatment targets in S pneumoniae meningitis. ANN NEUROL 2021;90:653-669.

Inter- and intra-observer variability in the selection of therapy for infantile hemangiomas among pediatric dermatologists in Spain.

BACKGROUND: Guidelines and expert recommendations on infantile hemangiomas (IH) are aimed at increasing homogeneity in clinical decisions based on the risk of sequelae. OBJECTIVE: The objective was to analyze the inter- and intra-observer agreement among pediatric dermatologists in the choice of treatment for IH. METHODS: We performed a cross-sectional inter-rater and intra-rater agreement study within the Spanish infantile hemangioma registry. Twenty-seven pediatric dermatologists were invited to participate in a survey with 50 clinical vignettes randomly selected within the registry. Each vignette contained a picture of an infantile hemangioma with a clinical description. Raters chose therapy among observation, topical timolol, or oral propranolol. The same survey reordered was completed 1 month later to assess intra-rater agreement. Vignettes were stratified into hemangioma risk categories following the Spanish consensus on IH. The agreement was measured using kappa statistics appropriate for the type of data (Gwet's AC1 coefficient and Gwet's paired t test). RESULTS: Twenty-four dermatologists completed the survey. Vignettes represented 7.8% of the Spanish hemangioma registry. The inter-rater agreement on the treatment decision was fair (AC1  = 0.39, 95% confidence interval [CI]: 0.30-0.47). When stratified by risk category, good agreement was reached for high-risk hemangiomas (AC1  = 0.77, 95% CI: 0.51-1.00), whereas for intermediate- and low-risk categories, the agreement was only fair (AC1 0.31, 95% CI: 0.16-0.46 and AC1  = 0.38, 95% CI: 0.27-0.48, respectively). Propranolol was the main option for high-risk hemangiomas (86.4%), timolol for intermediate-risk (36.8%), and observation for low-risk ones (55.9%). The intra-rater agreement was good. The inter-rater agreement between pediatric dermatologists on the treatment of IH is only fair. Variability was most significant with intermediate- and low-risk hemangiomas.

Acute systemic LPS-exposure impairs perivascular CSF distribution in mice.

BACKGROUND: The exchange of cerebrospinal (CSF) and interstitial fluid is believed to be vital for waste clearance in the brain. The sleep-dependent glymphatic system, which is comprised of perivascular flow of CSF and is largely dependent on arterial pulsatility and astrocytic aquaporin-4 (AQP4) expression, facilitates much of this brain clearance. During the last decade, several observations have indicated that impaired glymphatic function goes hand in hand with neurodegenerative diseases. Since pathologies of the brain carry inflammatory components, we wanted to know how acute inflammation, e.g., with lipopolysaccharide (LPS) injections, would affect the glymphatic system. In this study, we aim to measure the effect of LPS on perivascular CSF distribution as a measure of glymphatic function. METHODS: Three hours after injection of LPS (1 mg/kg i.p.), C57bl/6 mice were (1) imaged for two CSF tracers, injected into cisterna magna, (2) transcardially perfused with buffer, or (3) used for physiological readouts. Tracer flow was imaged using a low magnification microscope on fixed brains, as well as using vibratome-cut slices for measuring tracer penetration in the brain. Cytokines, glial, and BBB-permeability markers were measured with ELISAs, Western blots, and immunohistochemistry. Cerebral blood flow was approximated using laser Doppler flowmetry, respiration and heart rate with a surgical monitor, and AQP4-polarization was quantified using confocal microscopy of immunolabeled brain sections. RESULTS: LPS-injections significantly lowered perivascular CSF tracer flow and penetration into the parenchyma. No differences in AQP4 polarization, cytokines, astroglial and BBB markers, cerebral blood flow, or respiration were detected in LPS-injected mice, although LPS did elevate cortical Iba1+ area and heart rate. CONCLUSIONS: This study reports another physiological response after acute exposure to the bacterial endotoxin LPS, namely the statistically significant decrease in perivascular distribution of CSF. These observations may benefit our understanding of the role of systemic inflammation in brain clearance.

Autoimmune neutropenia associated with influenza virus infection in childhood: a case report.

BACKGROUND: Although neutropenia is relatively frequent in infants and children and is mostly a benign condition with a self-limited course, it can lead to life-threatening severe infections. Autoimmune neutropenia is a relatively uncommon hematological disorder characterized by the autoantibody-induced destruction of neutrophils. It is usually triggered by viral infections with very few documented cases after influenza virus. CASE PRESENTATION: An 8-month-old male infant presented at the emergency room with a 5-days history of fever up to 39.7 °C, cough and runny nose. In the blood test performed, severe neutropenia was diagnosed (neutrophils 109/µL). A nasopharyngeal aspirate revealed a positive rapid test for Influenza A. Serum antineutrophil antibodies were determined with positive results. Neutropenia targeted panel showed no mutations. Despite maintenance of severe neutropenia for 9 months the course was uneventful without treatment. CONCLUSIONS: When severe neutropenia is diagnosed and confirmed, it is essential to rule out some potential etiologies and underlying conditions, since the appropriate subsequent management will depend on it. Although autoimmune neutropenia triggered by viral infections has been widely reported, it has seldom been reported after influenza infection. The benign course of the disease allows a conservative management in most cases.

Chorea as the presenting feature of acute rheumatic fever in childhood; case reports from a low-prevalence European setting.

BACKGROUND: Despite a notable decrease in acute rheumatic fever (ARF) incidence in the past few decades, there are still cases in our setting. Sydenham chorea (SC) may be the initial manifestation for this condition in childhood in a significant proportion of children. We report two cases of choreoathetosis in children as the first manifestation of ARF. CASE PRESENTATION: A previously healthy 8-year-old boy presented with right hemichorea with a predominance in the brachial region, orofacial dyskinesias and speech difficulties for the past 2 weeks. The only medical history of interest was a common catarrhal illness 3 weeks before and nonspecific bilateral tenosynovitis in both feet since a year prior. A brain computerized tomography was normal and the echocardiogram showed mild mitral and aortic regurgitation, meeting ARF criteria. He demonstrated clinical improvement with treatment based on prednisone and carbamazepine. The second patient was a 10-year-old girl with choreic movements of the right half of the body and repetitive right eye closure of 1 week duration. She had symptoms of fever and rash the previous week and pharyngitis that resolved without antibiotic 2 months before. Blood tests revealed elevated C reactive protein (12 mg/dl) and erythrocyte sedimentation rate (96 mm/h). Brain magnetic resonance was normal and echocardiogram showed left ventricle dilation and mild mitral regurgitation, leading to the diagnosis of ARF. Due to neurological involvement, she received corticosteroids and intravenous immunoglobulin treatment, with worsening of neurological symptoms that required valproic acid with remission of the hemichorea. In addition skin lessions compatible with erythema marginatum appeared on the upper limbs. CONCLUSIONS: SC should be the main diagnostic consideration in cases of hemichorea with normal neuroimaging in children. The cases reported highlight the need to maintain a high index of suspicion even in settings where incidende of ARF is low and the need to perform cardiological investigations in all patients with suspected SC, due to the possibility of subclinical valve lesions. Good adherence to secondary prophylaxis is crucial to avoid chorea relapses and worsening valve disease.

Oral ingestion versus endoscopic delivery of endoscopic capsule in patients with previous gastrointestinal surgery (ORENCES study): A Spanish multicentre observational study.

BACKGROUND: Small Bowel Capsule Endoscopy is the first-choice technique for investigating the majority of small bowel diseases. Its most common complications are related to incomplete examinations and capsule retention. There is no consensus on how patients with previous gastrointestinal surgery should receive the capsule. OBJECTIVE: The primary endpoint was to compare the rate of complete small-bowel examinations (completion rate) between oral ingestion and endoscopic delivery of the capsule. The secondary endpoint was to compare diagnostic yield and adverse events in the two groups. METHODS: A retrospective observational study was conducted in nine hospitals in Spain. Demographic data, previous surgery, indication for capsule endoscopy, intestinal transit time, diagnosis, completion rate (percentage of capsules reaching the caecum), diagnostic yield (percentage of results compatible with indication for the exam) and adverse events were collected. RESULTS: From January 2009 to May 2019 fifty-seven patients were included (39 male, mean age 66±15 years). The most common indications for the exam were "overt" (50.9%) and "occult" (35.1%) small bowel bleeding. Previous Billroth II gastrectomy and Roux-en-Y gastric bypass were present in 52.6% and 17.5% of patients respectively. The capsule was swallowed in 34 patients and placed endoscopically in 23 patients. No significant differences were observed between the oral ingestion and endoscopic delivery groups in terms of completion rate (82.4% vs. 78.3%; p=0.742), diagnostic yield (41.2% vs. 52.2%; p=0.432) or small bowel transit time (301 vs. 377min, p=0.118). No capsule retention occurred. Only one severe adverse event (anastomotic perforation) was observed in the endoscopic delivery group. CONCLUSIONS: In our case series, there were no significant differences between oral ingestion and endoscopic delivery in terms of completion rate, diagnostic yield or safety. Being less invasive, oral ingestion of the capsule should be the first-choice method in patients with previous gastrointestinal surgery.

Role of colour-Doppler high-frequency ultrasonography in capillary malformation-arteriovenous malformation syndrome: a case series.

High-frequency ultrasonography (HFUS) represents a useful adjunct for dermatologists in the diagnosis of capillary malformation-arteriovenous malformation (CM-AVM) syndrome. We present a paediatric case series of 6 patients with confirmed RASA1 gene mutation in whom HFUS demonstrated AVM beneath cutaneous CM-like lesions greater than 1.5 cm.

Structure of a Spumaretrovirus Gag Central Domain Reveals an Ancient Retroviral Capsid.

The Spumaretrovirinae, or foamy viruses (FVs) are complex retroviruses that infect many species of monkey and ape. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. However, there is a paucity of structural information for FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. To probe the functional overlap of FV and orthoretroviral Gag we have determined the structure of a central region of Gag from the Prototype FV (PFV). The structure comprises two all α-helical domains NtDCEN and CtDCEN that although they have no sequence similarity, we show they share the same core fold as the N- (NtDCA) and C-terminal domains (CtDCA) of archetypal orthoretroviral capsid protein (CA). Moreover, structural comparisons with orthoretroviral CA align PFV NtDCEN and CtDCEN with NtDCA and CtDCA respectively. Further in vitro and functional virological assays reveal that residues making inter-domain NtDCEN-CtDCEN interactions are required for PFV capsid assembly and that intact capsid is required for PFV reverse transcription. These data provide the first information that relates the Gag proteins of Spuma and Orthoretrovirinae and suggests a common ancestor for both lineages containing an ancient CA fold.

Comorbidity between idiopathic overactive bladder and chronic migraine.

Objective We tested whether overactive bladder (OAB) and chronic migraine (CM) could be comorbid. Patients and methods CM women, aged 40-69 years, answered a validated OAB questionnaire. Prevalence data were compared with those reported in our country in the general population (GP) using the same questionnaire. Results We interviewed 231 CM women. Eighty-four met OAB criteria. OAB prevalence in CM patients was significantly higher than that found in the GP (36.4% vs. 21.8% in the GP; p = 0.0001). There were 34 CM women aged 40-49 years (34.3% vs. 15.2%; p = 0.001), 35 aged 50-59 years (38.9% vs. 21.7%; p = 0.004) and 15 aged 60-69 years (35.7% vs. 24.5%; p = 0.15) meeting OAB criteria. Seventy-seven (33% vs. 9.9%; p = 0.002) needed more than eight micturitions/24 h, 61 (26.4% vs. 8.1%, p = 0.002) experienced nocturia and 43 (18.6% vs. 8.1%; p = 0.001) urinary incontinence. Conclusion In this exploratory study, at least in women, OAB and CM are comorbid, which suggests shared mechanisms.

Self-assembly of bis-salphen compounds: from semiflexible chains to webs of nanorings.

The recently-observed self-assembly of certain salphen-based compounds into neuron-like networks of microrings interconnected with nano-thin strings may suggest a new highly-potent tool for nanoscale patterning. However, the mechanism behind such phenomena needs to be clarified before they can be applied in materials design. Here we show that, in contrast with what was initially presumed, the emergence of a "rings-and-rods" pattern is unlikely to be explained by merging, collapse and piercing of vesicles as in previously reported cases of nanorings self-assembly via non-bonding interactions. We propose an alternative explanation: the compounds under study form a 1D coordination polymer, the fibres of which are elastic enough to fold into toroidal globules upon solvent evaporation, while being able to link separate chains into extended networks. This becomes possible because the structure of the compound's scaffold is found to adopt a very different conformation from that inferred in the original work. Based on ab initio and molecular dynamics calculations we propose a step-by-step description of self-assembly process of a supramolecular structure which explains all the observed phenomena in a simple and clear way. The individual roles of the compound' s scaffold structure, coordination centres, functional groups and solvent effects are also explained, opening a route to control the morphology of self-assembled networks and to synthesize new compounds exhibiting similar behaviour.

Stereoselective Synthesis of Highly Substituted Tetrahydropyrans through an Evans Aldol-Prins Strategy.

A direct and general method for the synthesis of naturally occurring 2,3,4,5,6-pentasubstituted tetrahydropyrans has been developed, employing ß,γ-unsaturated N-acyl oxazolidin-2-ones as key starting materials. The combination of the Evans aldol addition and the Prins cyclization allowed the diastereoselective and efficient generation of the desired oxacycles in two fashions: a one-pot Evans aldol-Prins protocol, in which five new σ bonds and five contiguous stereocenters were straightforwardly generated, and a two-step version, which additionally permitted the isolation of ß,γ-unsaturated alcohol precursors bearing an N-acyl oxazolidin-2-one in the α position. From these alcohols were also obtained halogenated pentasubstituted tetrahydropyrans as well as 2,3,4,5-tetrasubstituted tetrahydrofurans, shedding light on the mechanism of the process. Computational studies were consistent with the experimental findings, and this innovative Evans aldol-Prins strategy was performed for the preparation of a battery of more than 30 densely substituted tetrahydropyrans, unprecedentedly fused to a 1,3-oxazinane-2,4-dione ring, both in a racemic fashion and in an enantiomeric fashion. These novel molecules were successfully submitted to several transformations to permit simple access to a variety of differently functionalized tetrahydropyrans. Most of these unique molecules were evaluated for their antimicrobial activity against Gram-positive and Gram-negative bacteria and the yeast Candida albicans, and some structure-activity relationships were established.

Infantile hemangioma with minimal or arrested growth as the skin manifestation of PHACE syndrome.

BACKGROUND: Infantile hemangiomas with minimal or arrested growth are vascular tumors with a proliferative component involving < 25% of their total surface area. They are commonly described as localized lesions and are mainly located on the lower body. Little has been described about segmental forms on the face and their associations with PHACE syndrome. METHODS: We carried out a multicenter, retrospective, case-series study involving 5 hospitals in Spain. Information was collected on cases of PHACE syndrome featuring infantile hemangiomas with minimal or arrested growth. RESULTS: The frontotemporal and maxillary areas were the most frequently involved sites in our series. The upper eyelid and upper lip were the 2 locations most frequently associated with proliferation and ulceration. Four patients experienced spontaneous resolution, and the rest had a very good cosmetic outcome with oral treatment. Cerebral and cervical arterial anomalies were the most frequent extracutaneous findings associated with PHACE, followed by cerebral and ocular anomalies. Some unique associated disorders were fructose intolerance and retinoblastoma. CONCLUSION: We present the largest case series of segmental facial infantile hemangiomas with minimal or arrested growth in PHACE syndrome and emphasize the importance of recognizing these lesions in early infancy, because they can indicate PHACE syndrome. The data presented suggest that infantile hemangiomas with minimal or arrested growth-associated PHACE syndrome does not seem to differ significantly from PHACE syndrome with classic infantile hemangiomas, and thus the same recommendations for diagnosis, management, and therapy should be followed. Future studies with more patients could contribute to enlighten this specific subset.

Detection of major food allergens in amniotic fluid: initial allergenic encounter during pregnancy.

BACKGROUND: Ingestion of food allergens present in maternal milk during breastfeeding has been hypothesized as a gateway to sensitization to food; however, this process could develop during pregnancy, as the maternal-fetal interface develops a Th2- and Treg-mediated environment to protect the fetus. We hypothesized that in these surroundings, unborn children are exposed to food allergens contained in the mother's diet, possibly giving rise to first sensitization. METHODS: The presence of allergens in utero was studied by analyzing amniotic fluid (AF) samples in two different stages of pregnancy: at 15-20 weeks and after delivery at term. An antibody microarray was developed to test for the most common food allergens. The array detects the presence of ten allergens from milk, fruit, egg, fish, nuts, and wheat. RESULTS: AF from 20 pregnant women was collected: eight after delivery at term and 12 from women who underwent diagnostic amniocentesis between weeks 15 and 20 of gestation. The presence of allergens was detected in all samples. Samples from amniocentesis had a higher allergen concentration than samples after delivery at term. CONCLUSIONS: We demonstrated the presence of intact major food allergens in AF samples. This early contact could explain subsequent sensitization to foods never eaten before.

A unique spumavirus Gag N-terminal domain with functional properties of orthoretroviral matrix and capsid.

The Spumaretrovirinae, or foamyviruses (FVs) are complex retroviruses that infect many species of monkey and ape. Although FV infection is apparently benign, trans-species zoonosis is commonplace and has resulted in the isolation of the Prototypic Foamy Virus (PFV) from human sources and the potential for germ-line transmission. Despite little sequence homology, FV and orthoretroviral Gag proteins perform equivalent functions, including genome packaging, virion assembly, trafficking and membrane targeting. In addition, PFV Gag interacts with the FV Envelope (Env) protein to facilitate budding of infectious particles. Presently, there is a paucity of structural information with regards FVs and it is unclear how disparate FV and orthoretroviral Gag molecules share the same function. Therefore, in order to probe the functional overlap of FV and orthoretroviral Gag and learn more about FV egress and replication we have undertaken a structural, biophysical and virological study of PFV-Gag. We present the crystal structure of a dimeric amino terminal domain from PFV, Gag-NtD, both free and in complex with the leader peptide of PFV Env. The structure comprises a head domain together with a coiled coil that forms the dimer interface and despite the shared function it is entirely unrelated to either the capsid or matrix of Gag from other retroviruses. Furthermore, we present structural, biochemical and virological data that reveal the molecular details of the essential Gag-Env interaction and in addition we also examine the specificity of Trim5α restriction of PFV. These data provide the first information with regards to FV structural proteins and suggest a model for convergent evolution of gag genes where structurally unrelated molecules have become functionally equivalent.

Coxsackievirus B3 mutator strains are attenuated in vivo.

Based on structural data of the RNA-dependent RNA polymerase, rational targeting of key residues, and screens for Coxsackievirus B3 fidelity variants, we isolated nine polymerase variants with mutator phenotypes, which allowed us to probe the effects of lowering fidelity on virus replication, mutability, and in vivo fitness. These mutator strains generate higher mutation frequencies than WT virus and are more sensitive to mutagenic treatments, and their purified polymerases present lower-fidelity profiles in an in vitro incorporation assay. Whereas these strains replicate with WT-like kinetics in tissue culture, in vivo infections reveal a strong correlation between mutation frequency and fitness. Variants with the highest mutation frequencies are less fit in vivo and fail to productively infect important target organs, such as the heart or pancreas. Furthermore, whereas WT virus is readily detectable in target organs 30 d after infection, some variants fail to successfully establish persistent infections. Our results show that, although mutator strains are sufficiently fit when grown in large population size, their fitness is greatly impacted when subjected to severe bottlenecking, which would occur during in vivo infection. The data indicate that, although RNA viruses have extreme mutation frequencies to maximize adaptability, nature has fine-tuned replication fidelity. Our work forges ground in showing that the mutability of RNA viruses does have an upper limit, where larger than natural genetic diversity is deleterious to virus survival.

[Is it possible to stop treatment with nucleos(t)ide analogs in patients with e-antigen negative chronic hepatitis B? Experience and new expectations]. / ¿Es posible suspender el tratamiento con antivirales orales en los pacientes con hepatitis crónica B antígeno e negativa? Experiencia y nuevas expectativas.

BACKGROUND: Treatment of HBeAg-negative chronic hepatitis B (CHB) with nucleos(t)ide analogues (NA) is usually indefinite, since the loss of HBsAg, as a criterion for its discontinuation, is a rare event. Recent evidence suggests that discontinuing NA therapy may be feasible in selected patients. OBJECTIVES: To analyze the rate of virological relapse in patients with HBeAg-negative CHB who discontinued treatment with NAs. METHODS: We performed a single-center observational study that included 140 patients with HBsAg-negative CHB. Twenty-two patients, who received only NAs, discontinued treatment for different reasons and were subsequently monitored. All had normal ALT and AST, undetectable DNA and absence of cirrhosis or significant comorbidities before stopping treatment. RESULTS: Twelve patients showed virologic relapse (54.54%). The mean interval between discontinuation and relapse was 6.38 months (± 1.9) (75% relapsed during the first 12 months after discontinuation). Five received adefovir, 1 lamivudine and adefovir, 1 tenofovir and 5 lamivudine alone. The mean treatment duration in this group was 38.5 months (± 4.5). The sustained response group had a higher mean age and longer treatment duration than patients with virologic relapse but these differences were not statistically significant. CONCLUSIONS: The results suggest that NA treatment can be stopped in selected patients with CHB as long as they are not cirrhotic, have completed a minimum period of treatment, have normal ALT and sustained undetectable DNA. These patients should be closely monitored during the first year and then indefinitely.