The impact of menopause on antidepressant response: an explorative analysis from a real-world study.

This study endeavors to deepen our understanding of the subject matter by exploring, within a real-world sample, the impact of menopausal status on the antidepressant treatments response. The whole sample included a total of 447 patients, 156 male and 291 female, 110 pre-menopause and 181 post-menopause. In our sample post-menopause women showed a worse response to antidepressants than pre-menopause women (p = 0.006), and this difference seems to be unrelated to age or brain aging.

How different definition criteria may predict clinical outcome in treatment resistant depression: Results from a prospective real-world study.

Management of treatment-resistant depression (TRD) remains a major public health challenge, also due to the lack of a consensus around TRD definition. We investigated the impact of different definitions of TRD on identifying patients with distinct features in terms of baseline characteristics, treatment strategies, and clinical outcome. We conducted a prospective naturalistic study on 538 depressed inpatients. Patients were screened for treatment resistance by two TRD definitions: looser criteria (lTRD) and stricter criteria (sTRD). We compared baseline characteristics, treatment and clinical outcome between the TRD groups and their non-TRD counterparts. 52.97 % of patients were identified as lTRD, only 28.81 % met the criteria for sTRD. sTRD patients showed lower rates of remission and slower symptom reduction compared to non-TRD patients and received more challenging treatments. Surprisingly, patients identified as sTRD also exhibited lower rates of psychiatric comorbidities, including personality disorders, substance abuse, or alcohol misuse. Stricter TRD criteria identify patients with worse clinical outcomes. Looser criteria may lead to overdiagnosis and over treatment. Clinical features known to be possible risk factors for TRD, as psychiatric comorbidities, showed to be more suggestive of a "difficult to manage" depression rather than a proper TRD.

Add-On Treatment with Passiflora incarnata L., herba, during Benzodiazepine Tapering in Patients with Depression and Anxiety: A Real-World Study.

Chronic and inappropriate benzodiazepine intake represents an important health and social concern worldwide. The aim of our study was to investigate the effectiveness of P. incarnata L., herba, in reducing benzodiazepine misuse in a real-world population of depressed and anxious patients in a long-term treatment with benzodiazepines. We conducted a retrospective naturalistic study on 186 patients undergoing benzodiazepine downtitration, 93 with the addition of a dry extract of P. incarnata L., herba (Group A), and 93 without any add-on treatment (Group B). Regarding the benzodiazepine dosage variation in the two groups, a repeated measure ANOVA showed a significant effect of time (p < 0.001), group (p = 0.018), and time x group interaction (p = 0.011). We found a significantly higher rate, i.e., of 50%, reduction in Group A vs. Group B at 1 month (p < 0.001) and at 3 months (p < 0.001) and complete benzodiazepine discontinuation at 1 month (p = 0.002) and at 3 months (p = 0.016). Our findings suggest the role of P. incarnata as an effective add-on treatment during benzodiazepine tapering. These findings highlight the need for further studies to better investigate the promising properties of P. incarnata in the management of such a relevant clinical and social issue.

Effects of pendulum appliance versus clear aligners in the vertical dimension during Class II malocclusion treatment: a randomized prospective clinical trial.

BACKGROUND: The aim of the present study was to compare the effects on vertical dentoskeletal dimension produced by Pendulum appliance and Clear Aligners in patients with Class II malocclusion. TRIAL DESIGN: This is a prospective two-arm parallel group randomized clinical trial with 1:1 allocation ratio. METHODS: The Pendulum Group (PG) consisted of 20 patients (15F, 5 M) with a mean age of 17.2 ± 4.3 years. The Clear Aligners Group (CAG) comprised 20 patients (13F, 7 M) with a mean age of 17.2 ± 3.2 years. Distalization's protocol in PG involved the activation of TMA wires till the achievement of Class I molar relationship. A protocol of sequential distalization was applied in the CAG. For each subject lateral cephalograms have been analyzed before treatment (T1) and at the end of the therapy (T2). Descriptive statistics and statistical between-group comparisons (PG vs CAG) were calculated for the craniofacial starting forms at T1 and for the T2-T1 changes. Statistical between-group comparisons for the T2-T1 changes were performed with independent samples t-tests (P < 0.05). RESULTS: The PG showed significantly greater increases in SN^GoGn° when compared with CAG (+ 2.1 and - 0.3 degrees, respectively). Clockwise rotation of the occlusal plane with significantly greater increase of SN^POccl angle was observed in PG (+ 2.8 degrees) when compared with CAG (- 4.2 degrees). The PG revealed a significant increase in the N-Me variable with a mean change of + 4.4 mm compared to the CAG with mean values of - 1.2 mm. The PG showed an increase in the ArGo^GoMe angle (+ 0.7° degrees) compared to the CAG (- 3.4° degrees). The PG showed significantly greater increases in both maxillary and mandibular first molar to palatal plane (+ 1.3 and + 2.1 mm, respectively) when compared with CAG (- 0.9 and - 0.2 mm, respectively). CONCLUSIONS: Upper molar distalization with clear aligners represents a valid alternative to non-extraction treatment of Class II malocclusion, reducing the extrusion of maxillary first molars and improving the management of the occlusal plane and vertical dimension. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05298280. Registered 28 March 2022-Retrospectively registered, https://clinicaltrials.gov .

Proactive Risk Assessment Through Failure Mode and Effect Analysis (FMEA) for Haemodialysis Facilities: A Pilot Project.

Haemodialysis (HD) is one of the methods for renal replacement therapy in the management of advanced chronic kidney disease through an osmosis process that allows purification of blood in the dialysis machine. The complexity of the dialytic procedure often requires the presence of a multi-specialist, multi-disciplinary team. The dialysis process is an important target for clinical risk management. Failure Mode and Effect Analysis (FMEA) is a proactive technique, considered a purposeful and dynamic tool for clinical risk management. FMEA is noted in five phases that allow a preliminary assessment of a definite process through identification and classification of risk priorities. This study represents the first of a two-phase project where FMEA is applied to HD in the setting of San Feliciano Hospital. The dialysis center performs ~12,000 dialysis sessions per year. The dialysis process is divided into different stages. A total of 31 failure modes were identified in the whole dialysis stages; more than 2/3 of the failure modes were related to the only connecting of the patient to the dialysis machine. The first phase of the study clearly remarked that the most critical step of the dialytic process is represented by the connection between the patient and the machine, as expected. Indeed, in order to have the dialysis set up, an arteriovenous fistula must be surgically created prior to the procedure and it is one of the most important issues in the HD process because of the necessity of a constant revision of it. FMEA application to HD is a useful tool, easy to be implemented and it is likely to nimbly reveal the practical and potential solutions to the critical steps of the procedure.

Thromboinflammatory response in SARS-CoV-2 sepsis.

Viral sepsis is rare, and its real incidence is not known. SARS-CoV-2 infection causes the release of a significant amount of pro-inflammatory cytokines that aggravates interstitial pneumonia and evolves in viral sepsis with prominent hypercoagulability. We believe it is useful and advisable to establish early immunomodulator therapy and the prophylaxis anticoagulant therapy should be rethought.

Post-Traumatic Meningitis Is a Diagnostic Challenging Time: A Systematic Review Focusing on Clinical and Pathological Features.

Post-traumatic meningitis is a dreadful condition that presents additional challenges, in terms of both diagnosis and management, when compared with community-acquired cases. Post-traumatic meningitis refers to a meningeal infection causally related to a cranio-cerebral trauma, regardless of temporal proximity. The PICO (participants, intervention, control, and outcomes) question was as follows: "Is there an association between traumatic brain injury and post-traumatic meningitis?" The present systematic review was carried out according to the Preferred Reporting Items for Systematic Review (PRISMA) standards. Studies examining post-traumatic meningitis, paying particular attention to victims of traumatic brain injury, were included. Post-traumatic meningitis represents a high mortality disease. Diagnosis may be difficult both because clinical signs are nonspecific and blurred and because of the lack of pathognomonic laboratory markers. Moreover, these markers increase with a rather long latency, thus not allowing a prompt diagnosis, which could improve patients' outcome. Among all the detectable clinical signs, the appearance of cranial cerebrospinal fluid (CSF) leakage (manifesting as rhinorrhea or otorrhea) should always arouse suspicion of meningitis. On one hand, microbiological exams on cerebrospinal fluid (CSF), which represent the gold standard for the diagnosis, require days to get reliable results. On the other hand, radiological exams, especially CT of the brain, could represent an alternative for early diagnosis. An update on these issues is certainly of interest to focus on possible predictors of survival and useful tools for prompt diagnosis.

Course of oesophageal varices and performance of noninvasive predictors following Hepatitis C Virus clearance in compensated advanced chronic liver disease.

BACKGROUND: In patients with hepatitis C virus (HCV) and compensated advanced chronic liver disease (cACLD), there is evidence that sustained virological response (SVR) to direct-acting antivirals (DAA) may ameliorate portal hypertension, although both the course of oesophageal varices and the performance of their noninvasive predictors following DAA-induced SVR are less defined. In this study, our aim was to assess the variation in oesophageal varices status in HCV patients with cACLD who obtained an SVR to DAAs and to evaluate the diagnostic performance of noninvasive predictors of varices after HCV cure. MATERIAL AND METHODS: Sixty-three HCV patients with cACLD and SVR to DAAs were prospectively followed up, and oesophageal varices surveillance was carried out according to the Baveno VI indications. Appearance and disappearance of varices, accuracy performance of their noninvasive predictors (Baveno/expanded Baveno VI criteria, platelet count/spleen diameter ratio) and number of endoscopies spared with their application were calculated. RESULTS: Following SVR, varices developed or disappeared in 12.1% and 17.4% of patients, respectively. The negative predictive value for varices of the Baveno VI, expanded Baveno VI criteria and platelet count/spleen diameter ratio following SVR was 88.2% (65.6-96.7), 83.3% (66.3-92.7) and 80.7% (67.1-89.5), respectively. Their application would have saved 30.4%, 42.9% and 55.4% of endoscopies, with no varices needing treatment missed using both Baveno VI criteria. CONCLUSIONS: In HCV patients with cACLD, following SVR to DAA, the expanded Baveno VI criteria provide the best balance between utility (diagnostic accuracy and endoscopies avoided) and safety (varices needing treatment missed) for varices surveillance.

Sudden death in acrogeria Gottron type.

In this paper, we describe the case of a 29-year-old Caucasian male who was reported dead in his home. In 2010, a diagnosis of acrogeria, Gottron type was obtained by genetic analysis of a COL3A1 gene mutation. External examination showed typical characteristics of acrogeria, Gottron type. Autopsy showed a full-thickness laceration in the inferior vena cava wall, which caused hemorrhage and death. Samples of inferior vena cava were processed by Masson trichrome staining, which revealed a reduction in vessel wall thickness and a decrease in the amount of elastic fibers. An antibody reaction with BCL-2 was intensely positive. Our case is extremely rare in the medical field and in the world of scientific literature, both because the patient had a variant of acrogeria, Gottron type and because of the cause of death, which is not typical of Ehlers-Danlos syndrome. To the best of our knowledge, this very rare event has not previously been reported in the international scientific literature.

Geometric morphometric analysis of the palatal morphology in growing subjects with skeletal open bite.

OBJECTIVES: To assess the morphological shape variations of the palatal vault in Open Bite (OB) growing subjects when compared with a Control Group (CG) by means of Geometric Morphometric Method (GMM). MATERIALS AND METHODS: The OB Group (OBG) consisted of 75 subjects (39 females, 36 males; mean age: 8.5 ± 0.8 years) who were collected retrospectively with the following inclusion criteria: European ancestry, overbite less than 0 mm, mixed dentition stage, prepubertal skeletal maturation (CS1-CS2), hyperdivergent skeletal pattern (SN^GoGn > 37°). The OBG was compared with a CG of 46 prepubertal subjects presenting normal occlusion (24 females, 22 males; mean age of 8.3 ± 1.7 years). For each subject, lateral cephalograms and maxillary dental casts were available. Landmarks and semilandmarks were digitized on digital dental casts and GMM was applied. Procrustes analysis and principal component analysis (PCA) were performed. OBG was divided in two subgroups: Sucking Habits Group (SHG) (39 subjects) and Non-Sucking Habits Group (NSHG) (36 subjects). RESULTS: PC1 showed significant morphological changes in transverse and vertical dimensions with OBG palates higher and narrower when compared with CG. When comparing the two subgroups no statistically significant differences were found. NSHG demonstrated a slight reduction of the transverse dimension and a deeper palatal vault respect to SHG. LIMITATIONS: The limitations of this study were the division of OBG in two subgroups based on referral of thumb sucking habits without assessing the duration and the intensity of thumb sucking. CONCLUSIONS: OB subjects presented with a significant constriction of the maxillary arch when compared with CG. The morphological palatal shape variations in OBG were not influenced by the presence or absence of non-nutritive sucking habits.

Erratum: Positive PET in a Patient With Esophageal Leiomyoma.

This corrects the article DOI: 10.1038/ajg.2016.205.

Low serum trough levels are associated with post-surgical recurrence in Crohn's disease patients undergoing prophylaxis with adalimumab.

BACKGROUND: Whether therapeutic drug monitoring of biologic therapy can predict the efficacy of adalimumab to prevent postoperative Crohn's disease recurrence is unknown. AIM: To investigate whether adalimumab trough levels and anti-adalimumab antibodies correlate with endoscopic and clinical outcomes in a series of patients treated with prophylactic adalimumab monotherapy after resective surgery. METHODS: Post hoc analysis of a randomized, mesalamine-controlled trial. Adalimumab trough levels and antibodies were analysed every 8 weeks for 2 years using an homogeneous mobility shift assay. RESULTS: At two years, 1/6 patient had clinical recurrence and 1/6 patient had endoscopic and clinical recurrence. At baseline (9.5 vs. 14.4 mcg/mL) and during follow-up [7.5 (4.4-9.8) vs. 13.9 (8.9-23.6)mcg/mL, p<0.01], median adalimumab trough levels in patients with clinical or endoscopic recurrence were lower than in those who maintained remission. Persistent antibodies-against-adalimumab were detected in the patient with both endoscopic and clinical recurrence. CONCLUSION: Measurement of adalimumab trough levels and anti-adalimumab antibodies after surgery could be useful to further reduce postoperative recurrence.

Adalimumab is more effective than azathioprine and mesalamine at preventing postoperative recurrence of Crohn's disease: a randomized controlled trial.

OBJECTIVES: Postsurgical recurrence of Crohn's disease (CD) is very frequent and, to date, only infliximab has been shown to be useful in preventing it. The efficacy of adalimumab (ADA) is poorly known. We evaluated whether the administration of ADA after resective intestinal surgery reduces postoperative CD recurrence. METHODS: We randomly assigned 51 patients with CD who had undergone ileocolonic resection to receive after 2 weeks from surgery ADA at the dose of 160/80/40 mg every two weeks, azathioprine (AZA) at 2 mg/kg/day, or mesalamine at 3 g/day, and they were followed up for 2 years. The primary end point was the proportion of patients with endoscopic and clinical recurrence. Secondary end point was the assessment of quality of life by means of a previously validated questionnaire. RESULTS: The rate of endoscopic recurrence was significantly lower in ADA (6.3%) compared with the AZA (64.7%; odds ratio (OR)=0.036 (95% confidence interval (CI) 0.004-0.347)) and mesalamine groups (83.3%; OR=0.013 (95% CI 0.001-0.143)). There was a significantly lower proportion of patients in clinical recurrence in the ADA group (12.5%) compared with the AZA (64.7%; OR=0.078 (95% CI 0.013-0.464)) and mesalamine groups (50%; (OR=0.143 (95% CI 0.025-0.819)). The quality of life was higher in the ADA (202) than in the AZA (90; OR=0.028 (95% CI 0.004-0.196)) and mesalamine groups (98; OR=0.015 (95% CI 0.002-0.134)). CONCLUSIONS: The administration of ADA after intestinal resective surgery was greatly effective in preventing endoscopic and clinical recurrence of CD. Further larger studies are necessary to confirm the therapeutic advantage and to show the economic implications of biologic therapy in this field.

Peripheral blood cytopaenia limiting initiation of treatment in chronic hepatitis C patients otherwise eligible for antiviral therapy.

BACKGROUND: In patients with chronic hepatitis C virus (HCV) infection, the presence of peripheral blood cytopaenia may represent an obstacle to pegylated interferon and ribavirin treatment. AIMS: To evaluate the prevalence of anaemia, neutropaenia and thrombocytopaenia potentially limiting initiation of pegylated interferon and ribavirin treatment in patients with chronic HCV infection who were otherwise eligible for antiviral therapy. METHODS: We studied 3059 consecutive anti-HCV and HCV-RNA positive patients referred to our centre to be evaluated for antiviral therapy from June 2002 to May 2011. The European Association for the Study of Liver HCV guidelines were applied to assess eligibility for antiviral therapy. RESULTS: In the study cohort, 1,521 patients (49.7%) were not eligible for treatment because of reasons different from haematological abnormalities. In the remaining 1,538 patients the overall prevalence of any peripheral blood cytopaenia potentially preventing patients from being treated with antiviral therapy was 15.1%. In particular, anaemia (haemoglobin level < 12 g/dL for women, <13 g/dL for men) was a relative contraindication to treatment in 8.9% (137/1,538) of the patients, while thrombocytopaenia (platelet count cut-off, 90 × 10(9) /L) and neutropaenia (absolute neutrophil count < 1.5 × 10(9) /L) limited treatment in 6.5% (100/1358) and 3.2% (48/1358) of patients respectively. These haematological abnormalities were more prevalent in patients with older age (P < 0.004) and cirrhosis (P < 0.001). CONCLUSIONS: The presence of peripheral blood cytopaenia may potentially limit initiation of antiviral therapy in one in every seven patients with chronic HCV infection who are otherwise eligible for treatment.

Activating NK cell receptor expression/function (NKp30, NKp46, DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment.

Specific NK cell killer inhibitory receptor (KIR):HLA haplotype combinations have been associated with successful clearance of acute and chronic HCV infection. Whether an imbalance of activating NK cell receptors also contributes to the outcome of treatment of chronic HCV infection, however, is not known. We studied peripheral NK cell phenotype and function in 28 chronically viraemic HCV genotype I treatment-naïve patients who underwent treatment with pegylated IFN-α and ribavirin. At baseline, chronically infected patients with sustained virological response (SVR) had reduced CD56(bright) CD16(+/-) cell populations, increased CD56(dull) CD16(+) NK cell proportions, and lower expression of NKp30, DNAM-1, and CD85j. Similarly, reduced NK cell IFN-γ production but increased degranulation was observed among nonresponding (NR) patients. After treatment, CD56(bright) CD16(+/-) NK cell numbers increased in both SVR and NR patients, with a parallel significant increase in activating NKp30 molecule densities in SVR patients only. In vitro experiments using purified NK cells in the presence of rIL-2 and IFN-α confirmed upregulation of NKp30 and also of NKp46 and DNAM-1 in patients with subsequent SVR. Thus, differences in patient NK cell receptor expression and modulation during chronic HCV-1 infection are associated with subsequent outcome of standard treatment. Individual activating receptor expression/function integrates with KIR:HLA genotype carriage to determine the clearance of HCV infection upon treatment.

Initial high dose of lamivudine delays the appearance of viral resistance in chronic hepatitis B patients.

BACKGROUND: The lamivudine dosage used for treatment of patients with hepatitis B virus (HBV) chronic liver disease is one-third of the dose used in patients infected with human immunodeficiency virus. Moreover, lamivudine therapy is hampered by the early and high rate of drug-resistance. AIM: To assess the effect of an initial high dose of lamivudine on the rate and temporal incidence of the development of resistance to treatment. METHODS: We retrospectively studied 62 patients (49 males; median age 54 years) with chronic HBV-related liver disease who were treated with lamivudine and who had at least 1-year on-treatment follow-up. Patients were subdivided according to the lamivudine dosage: 25 patients were treated with lamivudine 300 mg qd for two weeks, then shifted to 100mg qd (high-dose group) and 37 patients were treated with the standard dose of 100mg qd (standard-dose group). RESULTS: Median treatment duration was 45 months. As far as baseline HBV-DNA, HBeAg status, stage of disease, and previous interferon treatment are concerned there were no differences between groups. Viral resistance was detected in 43 patients (69%) after a median of 27 months (range: 6-72) with no significant difference between groups (high-dose, 60% versus standard-dose, 76%). Appearance of viral resistance was significantly delayed in the high-dose group (p=0.0274). CONCLUSIONS: This study has shown that an initial high dose of lamivudine is able to delay the appearance of viral resistance in patients with chronic HBV infection, thus suggesting that the genetic barrier of lamivudine could be dose-dependent.