Gut barrier-microbiota imbalances in early life lead to higher sensitivity to inflammation in a murine model of C-section delivery.

BACKGROUND: Most interactions between the host and its microbiota occur at the gut barrier, and primary colonizers are essential in the gut barrier maturation in the early life. The mother-offspring transmission of microorganisms is the most important factor influencing microbial colonization in mammals, and C-section delivery (CSD) is an important disruptive factor of this transfer. Recently, the deregulation of symbiotic host-microbe interactions in early life has been shown to alter the maturation of the immune system, predisposing the host to gut barrier dysfunction and inflammation. The main goal of this study is to decipher the role of the early-life gut microbiota-barrier alterations and its links with later-life risks of intestinal inflammation in a murine model of CSD. RESULTS: The higher sensitivity to chemically induced inflammation in CSD mice is related to excessive exposure to a too diverse microbiota too early in life. This early microbial stimulus has short-term consequences on the host homeostasis. It switches the pup's immune response to an inflammatory context and alters the epithelium structure and the mucus-producing cells, disrupting gut homeostasis. This presence of a too diverse microbiota in the very early life involves a disproportionate short-chain fatty acids ratio and an excessive antigen exposure across the vulnerable gut barrier in the first days of life, before the gut closure. Besides, as shown by microbiota transfer experiments, the microbiota is causal in the high sensitivity of CSD mice to chemical-induced colitis and in most of the phenotypical parameters found altered in early life. Finally, supplementation with lactobacilli, the main bacterial group impacted by CSD in mice, reverts the higher sensitivity to inflammation in ex-germ-free mice colonized by CSD pups' microbiota. CONCLUSIONS: Early-life gut microbiota-host crosstalk alterations related to CSD could be the linchpin behind the phenotypic effects that lead to increased susceptibility to an induced inflammation later in life in mice. Video Abstract.

Cambios en el dolor y el posicionamiento craneocervical en pacientes con trastornos temporomandibulares de origen miofascial tratados con terapia miofuncional / Changes in pain and craniocervical positioning in patients with temporomandibular disorders of myofascial origin treated with myofunctional therapy

Antecedentes: La asociación entre el posicionamiento craneocervical (PCC) y los trastornos temporomandibulares (TTM) ha sido intensamente investigada, pero todavía hay controversias entre clínicos e investigadores. Objetivo: Analizar los cambios en el dolor y el PCC en pacientes con TTM de origen miofascial tratados con terapia miofuncional. Método: Estudio experimental, longitudinal y prospectivo. Se evaluaron 16 pacientes de ambos sexos, edad promedio 31,62±10,61 años, con diagnóstico de TTM de origen miofascial (según los criterios diagnósticos para la investigación de los TTM), que habían recibido 10 sesiones de MAR grado ivde Maitland de la articulación temporomandibular combinadas con el uso de un dispositivo interoclusal de descompresión articular. Antes y después de esa intervención se evaluó: el PCC por fotografía analizada a través del programa SAPO; dolor espontáneo y dolor a la presión. Se analizó la normalidad de las variables mediante la prueba de Shapiro-Wilks. Para las comparaciones antes-después se aplicó la prueba t de Student para muestras pareadas. Se consideró significativo un valor p<0,05. Resultado: Se observó una disminución estadísticamente significativa del dolor espontáneo y a la presión. No se encontraron diferencias en las variables del PCC (p<0,05). Conclusión: Luego del tratamiento con MAR grado iv de Maitland de la articulación temporomandibular y el dispositivo interoclusal de descompresión articular, se observó una disminución estadística y clínicamente significativa del dolor espontáneo y a la presión. No se encontraron diferencias en las variables del PCC.

Background: The association between craniocervical positioning (CCP) and temporomandibular disorders (TMD) has been intensively investigated but there are still controversies between clinicians and researchers. Objective: To analyze the changes in pain and CCP in patients with TMD of myofascial origin treated with myofunctional therapy. Method: Experimental, longitudinal and prospective study. Sixteen patients of both sexes were included, mean age 31.62±10.61 years, with a diagnosis of TMD of myofascial origin (according to diagnostic criteria for investigation of TMD). They received 10 sessions of Maitland grade iv MAR of the temporomandibular joint combined with the use of an interocclusal joint decompression device before and after treatment. The following were evaluated: the PCC by photography analyzed through the SAPO program; spontaneous pain and pain on pressure. The normality of the variables was evaluated using the Shapiro-Wilks Test. For the before-after comparisons, the Student's t test was applied for paired samples. A P<.05 was considered significant. Result: There is a statistically significant decrease in spontaneous pain and pressure. No differences were found in the PCC variables (P<.05). Conclusion: After treatment with Maitland grade iv MAR of the temporomandibular joint and interocclusal joint decompression device, a statistically and clinically significant decrease in spontaneous pain and pressure is shown. No differences were found in the PCC variables.

Immediate effects of rhythmic joint mobilization of the temporomandibular joint on pain, mouth opening and electromyographic activity in patients with temporomandibular disorders.

BACKGROUND: Rhythmic joint mobilizations (RJM) of the temporomandibular joint (TMJ) are employed to relieve pain and improve function in patients with temporomandibular disorders (TMD). However, the evidence on the immediate effects of RJM in patients with TMD is scarce. The aim of this study was to assess the immediate clinical and functional effects of RJM in patients with TMD. MATERIALS AND METHODS: This was a one-group quasi-experimental before and after study. Thirty-eight patients with TMD were assessed by means of pain intensity (visual analogue score, VAS), pressure pain threshold (PPT, measured through pressure algometry on the masseter and temporal muscles), mouth opening (MO, measured with a ruler), and surface electromyographic activity of the masseter and temporal muscles (asymmetry index, AI). Measurements were performed before and after a single, 1-min session of RJM of each TMJ. All statistical analyses were performed using the SPSS version 20.0 statistical package. RESULTS: A statistical significant difference was found in pain intensity, PPT and MO after the intervention (p < 0.05). No difference was found in the AI. A large effect size was observed for pain intensity, PPT of the left and right masseter muscles and MO (d = 0.85-1.13), whereas for the left and right temporal muscles the effect size was moderate (d = 0.62) and small, respectively (d = 0.49). CONCLUSION: In this sample of patients with TMD, a single session of RJM of the TMJ seemed to be effective in reducing pain intensity, increasing PPT and improving MO immediately after the intervention, without differences in the AI.

Views of Schizophrenia Among Future Healthcare Professionals: Differences in Relation to Diagnostic Labelling, Causal Explanations, and Type of Academic Degree Program.

OBJECTIVE: Stereotyped beliefs about schizophrenia are well-established in the society and relatively common among healthcare professionals and students. The aim of this study was to investigate the opinions about the causes, treatment, and outcome of schizophrenia among healthcare students. METHOD: Undergraduate nursing and psychology students completed selected items of the Opinion on Mental Illness Questionnaire after reading a clinical vignette of undiagnosed schizophrenia. RESULTS: Students who labelled the description as schizophrenia were more pessimistic regarding full recovery from the disorder. Those who acknowledged greater relevance to biogenetic risk factors were more convinced of the efficacy of medications. Respondents' opinions on the efficacy of psychological interventions were more positive among psychology students than among nursing students. CONCLUSIONS: The study confirmed the associations of schizophrenia labelling with prognostic pessimism and beliefs about the efficacy of pharmacological treatment among future healthcare professionals. Students' opinions were less influenced by differences between academic degree programs. Information about current recovery rate and comprehensive care for schizophrenia may support future healthcare professionals in the relationship and the clinical management of PWS.

Haploidentical HSCT with post transplantation cyclophosphamide versus unrelated donor HSCT in pediatric patients affected by acute leukemia.

T-cell replete hematopoietic stem cell transplantation (HSCT) from a haploidentical donor followed by high doses of cyclophosphamide has been demonstrated to provide the best chances of a cure for many children in need of an allograft but who lack both a sibling and an unrelated donor. In this study we retrospectively compared the outcome of pediatric patients undergoing T-replete haploidentical HSCT (Haplo) for acute leukemia with those undergoing transplantation from unrelated HLA-matched donor (MUD) and HLA mismatched unrelated donor (MMUD) from 2012 to 2017 at our Center. Both univariable and multivariable analyses showed similar 5-year overall survival rates for MUD, MMUD, and Haplo patients: 71% (95% CI 56-86), 72% (95% CI 55-90), and 75% (95% CI 54-94), respectively (p = 0.97). Haplo patients showed reduced event-free survival rates compared to MUD and MMUD patients: 30% (95% CI 12-49) versus 70% (95% CI 55-84) versus 53% (95% CI 35-73), respectively (p = 0.007), but these data were not confirmed by a multivariable analysis. Non-relapse mortality (NRM) and relapse incidence (RI) were similar for the three groups. Therefore, our data confirm that Haplo is a suitable clinical option for pediatric patients needing HSCT when lacking both an MUD and an MMUD donor.

KRD (carfilzomib and lenalidomide plus dexamethasone) for the treatment of relapsed or refractory multiple myeloma in the real-life: a retrospective survey in 123 patients.

From April 2016, carfilzomib, in combination with lenalidomide and dexamethasone (KRD), became available for use in the daily practice in Italy for patients with relapsed or refractory multiple myeloma (RRMM). We performed a retrospective survey at 14 different institutions from Southern Italy in order to evaluate patient characteristics and treatment results from an unselected series of patients treated accordingly so far. One hundred and twenty-three consecutive patients were included, with a median of 2 previous lines of therapy (range 1-9) and a median age of 63 years (range 39-82). At the time of analysis, median number of courses administered is 11 (range 1-34), and all patients are evaluable for response. Overall response rate including complete remission, very good partial remission, and partial remission is 85%. After a median follow-up of 27 months, median overall and progression-free survival are 33 and 23 months, respectively. Sixty-three patients are alive and between them, 45 (37%) are in continuous remission. Sixty patients have died (49%), mainly from progressive disease. There were 6 treatment-related deaths (5% of the whole patient population). Overall, hematological and non-hematological toxicity were manageable, mostly on outpatient basis. Arterial hypertension has been observed in 43 cases (35%) but did not lead to treatment interruption. Our data demonstrate that in real life, KRD is highly effective and well tolerated in the majority of patients with RRMM.

Gut microbiome structure and adrenocortical activity in dogs with aggressive and phobic behavioral disorders.

Accompanying human beings since the Paleolithic period, dogs has been recently regarded as a reliable model for the study of the gut microbiome connections with health and disease. In order to provide some glimpses on the connections between the gut microbiome layout and host behavior, we profiled the phylogenetic composition and structure of the canine gut microbiome of dogs with aggressive (n = 11), phobic (n = 13) and normal behavior (n = 18). Hormones' determination was made through Radio Immuno-Assay (RIA), and next generation sequencing of the V3-V4 gene region of the bacterial 16S rRNA was employed to determine gut microbiome composition. Our results did not evidence any significant differences of hormonal levels between the three groups. According to our findings, aggressive behavioral disorder was found to be characterized by a peculiar gut microbiome structure, with high biodiversity and enrichment in generally subdominant bacterial genera (i.e. Catenibacterium and Megamonas). On the other hand, phobic dogs were enriched in Lactobacillus, a bacterial genus with known probiotic and psychobiotic properties. Although further studies are needed to validate our findings, our work supports the intriguing opportunity that different behavioral phenotypes in dogs may be associated with peculiar gut microbiome layouts, suggesting possible connections between the gut microbiome and the central nervous system and indicating the possible adoption of probiotic interventions aimed at restoring a balanced host-symbiont interplay for mitigating behavioral disorders.

A Systematic Review of Outcomes and Patient Satisfaction Following Surgical and Non-surgical Treatments for Hair Loss.

INTRODUCTION: This systematic review aims to examine surgical and non-surgical treatments and identify those procedures that are most effective in terms of patient satisfaction. MATERIALS AND METHODS: A systematic review protocol was developed a priori in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. The search was conducted in accordance with the PRISMA guidelines, the Cochrane handbook. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, and Cochrane databases was performed to identify studies on hair loss causes and hair loss treatment with different surgical and non-surgical techniques RESULTS: Our search generated a total of 781 articles; 646 studies were excluded based on the content of the abstracts, and an additional 105 studies were excluded based on the content of the complete article. We performed a review of the 30 remaining studies, which had sufficient data for inclusion, and met all the aforementioned inclusion criteria. Of the 30 studies, four were about minoxidil, four about finasteride, two about dutasteride, three about phototherapy, six about platelet-rich plasma injection, four about follicular unit transplantation technique, six about follicular unit extraction technique, and one about patient satisfaction following surgical treatment without a specified surgical technique. Only three studies used a patient-reported outcome measurement. CONCLUSIONS: Our study is the first comprehensive systematic review of hair loss, looking at the problem from different points of view, and focusing on finding the best solution for the patient. In the literature, there is currently no algorithm for the management of patients who go to a plastic surgeon for a solution to the problem of hair loss. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Oral health-related quality of life in children using the child perception questionnaire CPQ11-14: a review.

OBJECTIVES: The Child Perceptions Questionnaire 11-14 (CPQ11-14) is the most common and effective indicator of paediatric oral health-related quality of life. The aim of this review was to verify if CPQ11-14 can be considered a valid instrument for assessing the impact of oral health on the quality of life of adolescents for the paediatric population aged between 11 and 14 years old and which dental conditions mainly affect it. STUDY DESIGN: A literature research from Pubmed Medline database was adopted to identify the eligible studies among the published articles related to CPQ 11-14 using keyword search strategy. From 170 initial articles, a total of 128 articles were included for the full text reading. RESULTS: Conditions that mainly interest the oral health-related quality of life are untreated dental caries, dental trauma, increased dental protrusion, wearing orthodontic appliances, and severe periodontal disease. CONCLUSION: CPQ 11-14 seems to be a solid and valid indicator to measure oral health-related quality of life, because it has been widely tested and validated in several states including developed, developing and underdeveloped countries.

Treatment of Severe Gynecomastia After Massive Weight Loss: Analysis of Long-Term Outcomes Measured with the Italian Version of the BODY-Q.

INTRODUCTION: The objectives of this study are: (1) comparison of long-term outcomes after correction of severe gynecomastia using different techniques; (2) apply the Italian version of the BODY-Q; (3) present the role of intercostal perforator flap (ICAP) after massive weight loss for correction of severe gynecomastia. MATERIALS AND METHODS: Between January 2008 and March 2016, we performed surgical correction of bilateral severe gynecomastia in 80 men (160 breasts) following massive weight loss. Patients answered the Italian version of BODY-Q postoperative module. All patients had experienced substantial weight loss (> 30 kg), presented with bilateral severe tissue ptosis of the breast, follow-up of almost 2 years and had a good understanding of the Italian language, and signed consents were included in the study. The sample was studied about age, BMI, comorbidity, bariatric surgical procedure, follow-up, type of post-bariatric surgical procedure, complications and secondary procedures. RESULTS: We performed 487 severe gynecomastia corrections from 2008 to 2016; 80 patients adhered to the inclusion criteria and formed our study group. This cross-sectional study compared three cohorts: 52 access using a circumareolar scar, 18 with an inframammary fold scar, 10 with an inframammary fold scar using intercostal perforator flaps. There were 16 secondary procedures in group one, 2 in group two and 1 in group three. We compared the secondary procedures of group 1 with the other groups, and we obtained a significant difference with a P = 0.04. The mean patient age was 36.5 years, and the average body mass index was 27.5 kg/m2 at the time of surgical correction of gynecomastia. From the BODY-Q analysis, the group of patients undergoing adenomammectomy with inframammary fold scar using intercostal perforator flaps has achieved significantly better results regarding the satisfaction with chest, psychosocial function, satisfaction with outcome and better body image. CONCLUSIONS: This is the first study that used the BODY-Q to analyze the correction of severe gynecomastia following massive weight loss with long-term results. The use of this patient-reported outcome measure underlined that the intercostal artery perforator flap, used in the correction of severe gynecomastia following massive weight loss, is a safe and effective technique with good outcomes and high patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Patient-Reported Satisfaction Following Post-bariatric Surgery: A Systematic Review.

INTRODUCTION: The aims of our study were to identify studies that evaluated patient satisfaction following post-bariatric surgery, analyse existing questionnaires, and summarise their development, psychometric properties, and content. PATIENTS AND METHODS: A multistep search was undertaken on the web-based PubMed database from the National Library of Medicine to identify studies on patient satisfaction and quality of life following post-bariatric surgery. The authors summarised all the questionnaires used in every study and categorised them as generic, surgery specific, or ad hoc, and whether they contained either validated or unvalidated measures. RESULTS: Our search generated a total of 1754 articles. We performed a systematic review of the 12 remaining studies, because these had sufficient data and met the inclusion criteria. All the studies identified from the literature review were assessed to determine the type of surgery used, and whether or not the questionnaire used to analyse patient satisfaction had been validated. The questionnaires were analysed by reviewers to assess adherence to the rules of the US Food and Drug Administration and the Scientific Advisory Committee of the Medical Outcomes Trust. We identified 20 individual questionnaires that included 10 generic instruments that assessed quality of life, six instruments specific for post-bariatric surgery, three instruments specific for breast surgery. CONCLUSIONS: In post-bariatric patients, the BODY-Q was shown to be a more objective and confident measure for evaluating the quality of life of patients following post-bariatric surgery. LEVEL OF EVIDENCE III: For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Role of Appearance: Definition of Appearance-Pain (App-Pain) and Systematic Review of Patient-Reported Outcome Measures Used in Literature.

INTRODUCTION: The objectives of the current study were: (1) to perform a systematic review of the existing scientific literature on appearance and any subsequently related disorders and (2) to research in the literature the correlation between the role of appearance and patient's disease. MATERIALS AND METHODS: A systematic review protocol was developed a priori in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidance. A multistep search of the PubMed, MEDLINE, PreMEDLINE, Embase, Ebase, CINAHL, PsychINFO and Cochrane databases was performed to identify studies on patient satisfaction, quality of life, and body image. RESULTS: Our search generated a total of 347 articles. We performed a systematic review of the 18 studies, which had sufficient data and met all inclusion criteria. All studies identified from the literature review were assessed to determine the utilization of validated patient satisfaction questionnaires. The questionnaires were analyzed by reviewers to assess adherence to the rules of the US Food and Drug Administration and the Scientific Advisory Committee of the Medical Outcomes Trust. We identified 27 individual questionnaires. We summarized development and validation characteristics and content of the 27 validated measures used in the studies. CONCLUSIONS: This is the first systematic review to identify and critically appraise patient-reported outcome measures for appearance and body image using internationally accepted criteria. DAS59 was deemed to have adequate levels of methodological and psychometric evidence. We also introduced the concept of Appearance-Pain which consists of the recomposed systematic view of the experimental indicators of suffering, linked to one of the dimensions of appearance. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Neurocritical Patient Characteristics Related to Brain Death.

BACKGROUND: The lack of viable organs for transplantation led to the creation in Argentina of the Glasgow 7 Program based on the detection and follow-up of acute neurologic patients admitted with Glasgow scores ≤7 in selected hospitals. The objective of this study was to determine the likelihood of hospitalized acute neurologic patients progressing to brain death (BD) based on several variables, including age, sex, and admission diagnosis. METHODS: This study was a retrospective cohort analysis of data obtained from the SINTRA (Procurement and Transplantation National Information System) database between 2006 and 2015. Independent variables included the following: age, sex, and diagnosis at admission; ischemic stroke; spontaneous intracerebral hematoma (SIH); subarachnoid hemorrhage (SH); anoxia, meningitis; penetrating head injury (PHI); closed head injury; and tumors. A multivariate analysis was performed adjusting the diagnosis at admission according to age and sex. RESULTS: A total of 31,877 patients were included: 19,308 (61%) patients died and 9736 (30%) evolved to BD. Overall, 36% of women and 28% of men evolved to BD (relative risk, 0.87 [95% confidence interval (CI), 0.86-0.89]; P < .001). In the multivariate analysis adjusted for age and sex, we observed the following: SIH OR, 1.79 (95% CI, 1.69-1.9; P < .001); ischemic stroke OR, 0.82 (95% CI, 0.73-0.92; P < .001); SH OR, 2.33 (95% CI, 2.16-2.52; P < .001); anoxia OR, 0.71 (95% CI, 0.64-0.79; P < .001); closed head injury OR, 0.41 (95% CI, 0.38-0.43; P < .001); PHI OR, 2.64 (95% CI, 2.38-2.94; P < .001); and tumors OR, 1.07 (95% CI, 0.93-1.24; P = .31). CONCLUSIONS: Thirty percent of the patients who entered the Glasgow 7 Program evolved with BD. The characteristics most likely to result in BD were age, female sex, PHI, SH, and SIH.

Analysis of Symmetry Stability Following Implant-Based Breast Reconstruction and Contralateral Management in 582 Patients with Long-Term Outcomes.

INTRODUCTION: This study aimed to analyse the long-term outcomes following breast reconstruction and contralateral management to evaluate the stability of breast symmetry and patient satisfaction. MATERIALS AND METHODS: The study population consisted of women who had undergone implant-based monolateral breast reconstruction and contralateral management. Patients answered the BREAST-Q reconstruction module. Two reviewers analysed the post-operative outcomes of the patients included and compiled the Kroll Scale. Patients were divided into three groups: implant-based contralateral management, breast reduction and mastopexy. The Fisher's exact test was applied to the results. RESULTS: From the BREAST-Q analysis, the group of patients undergoing contralateral breast augmentation achieved significantly better results regarding the ability to wear clothing (p â‰ª 0.001), symmetry (p â‰ª 0.001), psychosocial well-being (p â‰ª 0.001) and physical well-being (p â‰ª 0.001). From the analysis of the Kroll Scale, the group of implant-based contralateral management received the highest score for symmetry (p â‰ª 0.001), shape (p â‰ª 0.001) and aesthetic result overall (p â‰ª 0.001). CONCLUSIONS: This study was the first to use BREAST-Q to analyse the stability of breast symmetry following breast reconstruction with long-term results. The implant-based contralateral management was the most effective procedure for achieving a stable and lasting result to obtain the high satisfaction of patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mastopexy on Reconstructed Breast Following Massive Weight Loss: An Innovative Technique Using Dermo-Capsular Flaps.

BACKGROUND: We have developed a dermo-capsular flap mastopexy technique for patients who have experienced massive weight loss after breast reconstruction. The aim of this technique is to lift the inframammary fold, adequately cover the implant, and remove excess skin, elevating the breast and obtaining symmetry with the contralateral breast. METHODS: Between January 2014 and February 2017, we performed this technique on 20 women who were candidates for second-stage breast reconstruction following nipple-sparing mastectomy. All patients had experienced substantial weight loss (> 15 kg) and presented with ptosis after first-stage reconstruction. RESULTS: There were 8 patients with bilateral reconstruction following bilateral mastectomy (4 with bilateral nipple-sparing mastectomy). There were 12 patients with unilateral mastectomy, all with contralateral breast ptosis treated by augmentation via inverted-T mastopexy (n = 7) or crescent mastopexy (n = 5). The average lift of the nipple-areola complex was 5 cm (range 2-8 cm). The average follow-up was 12 months (range 4-36 months). Two patients had complications, including partial wound dehiscence (in a heavy smoker) and recurrence of breast asymmetry. CONCLUSIONS: Implant breast reconstruction after massive weight loss is still possible even in the setting of thin, ptotic, and anelastic breast tissue. Our inverted-T dermo-capsular flap mastopexy technique for reconstructed breast is safe and effective with good outcomes and high patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A different perspective on sofosbuvir-ledipasvir treatment of patients with HCV genotype 1b cirrhosis: The ital-c network study.

The effectiveness of a 12-week course of sofosbuvir-ledipasvir in treatment-experienced HCV genotype 1b-infected patients with cirrhosis is still under debate. Our primary endpoint was to compare the sustained virological response at post-treatment week 12 (SVR12) of sofosbuvir-ledipasvir in combination with ribavirin for 12 weeks, and sofosbuvir-ledipasvir alone for 24 weeks. This was a prospective observational study that enrolled 424 (195 naive, 229 experienced; 164 treated for 12 weeks with Ribavirin and 260 with sofosbuvir-ledipasvir alone for 24 weeks) consecutive HCV genotype 1b-infected patients with cirrhosis. The SVR12 rates were 93.9% and 99.2% in patients treated for 12 and 24 weeks, respectively (P = .002). The baseline characteristics of patients treated for 12 weeks were significantly different from those treated for 24 weeks as regards their younger age (P = .002), prevalence of Child-Pugh class A (P = .002), lower MELD scores (P = .001) and smaller number of nonresponders (P = .04). The shorter treatment was significantly associated with a lower SVR12 in univariate and multivariate analyses (P = .007 and P = .008, respectively). The SVR rate was unaffected by age, gender, BMI, Child-Pugh class, MELD score or previous antiviral treatment. Patients receiving ribavirin experienced more episodes of ascites and headache but less recurrence of hepatocellular carcinoma (HCC), and were prescribed more diuretics and cardiopulmonary drugs. No patient discontinued treatment. The therapeutic regimen of sofosbuvir-ledipasvir plus ribavirin administered for 12 weeks was less effective than sofosbuvir-ledipasvir alone given for 24 weeks. At odds with European guidelines, the recommended 12-week treatment with sofosbuvir-ledipasvir alone might be suboptimal for this setting of patients.