Using the body when there are no words for feelings: alexithymia and somatization in self-harming adolescents

The present case-control study aimed to investigate the relationship between alexithymia and somatic complaints in the psychopathological setting of non-suicidal self-injury (NSSI). A clinical sample of 134 adolescents (115 females; 85.5%) from 12 to 18 years old engaging in NSSI was compared with a control group of 243 high-school students (157 females; 64.6%) from 13 to 18 years old. Data were collected using two questionnaires: The Youth Self-Report 11\u201318 and the 20 Toronto Alexithymia Scale. In both cases and controls, the presence of somatization and alexithymia was associated with more severe psychopathological problems. Analyses were conducted to explore the association between somatic disorders and alexithymia. In the clinical group, somatic complaints were reported by 95.9% of alexithymic individuals, whereas only 44.3% of alexithymic adolescents reported somatic complaints. A one-way relationship emerged between somatization and alexithymia: while alexithymia would seem to be a factor associated with self-injury, somatic disorders were strongly associated with alexithymia, but not necessarily with self-injury. Among the self-harming adolescents, those with both alexithymia and somatization had a more severe psychopathological picture than the individuals with alexithymia but no somatization. This would suggest that, in the setting of NSSI, greater difficulty with identifying feelings is associated with somatization, and alexithymia would be an attribute common to self-harming behavior and somatization, both of which are characterized by the body being used to express psychological and emotional problems. Future research could further investigate alexithymia in self-harming individuals, in relation to any presence or absence of somatic disorders, with longitudinal assessments on any differences in their manifestation of self-injury and its psychopathological correlates

HDV can constrain HBV genetic evolution in hbsag: Implications for the identification of innovative pharmacological targets

Chronic HBV + HDV infection is associated with greater risk of liver fibrosis, earlier hepatic decompensation, and liver cirrhosis hepatocellular carcinoma compared to HBV mono-infection. However, to-date no direct anti-HDV drugs are available in clinical practice. Here, we identified conserved and variable regions in HBsAg and HDAg domains in HBV + HDV infection, a critical finding for the design of innovative therapeutic agents. The extent of amino-acid variability was measured by Shannon-Entropy (Sn) in HBsAg genotype-D sequences from 31 HBV + HDV infected and 62 HBV mono-infected patients (comparable for demographics and virological-parameters), and in 47 HDAg genotype-1 sequences. Positions with Sn = 0 were defined as conserved. The percentage of conserved HBsAg-positions was significantly higher in HBV + HDV infection than HBV mono-infection (p = 0.001). Results were confirmed after stratification for HBeAg-status and patients’ age. A Sn = 0 at specific positions in the C-terminus HBsAg were correlated with higher HDV-RNA, suggesting that conservation of these positions can preserve HDV-fitness. Conversely, HDAg was characterized by a lower percentage of conserved-residues than HBsAg (p < 0.001), indicating higher functional plasticity. Furthermore, specific HDAg-mutations were significantly correlated with higher HDV-RNA, suggesting a role in conferring HDV replicative-advantage. Among HDAg-domains, only the virus-assembly signal exhibited a high genetic conservation (75% of conserved-residues). In conclusion, HDV can constrain HBsAg genetic evolution to preserve its fitness. The identification of conserved regions in HDAg poses the basis for designing innovative targets against HDV-infection

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production &gt;99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p&lt;0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted \u3b4 and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted \u3bb, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p&lt;0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p&lt;0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p &lt; 0.001), M133I (20.6% vs. 3.9%, p &lt; 0.001), and Q181E (11.8% vs. 0.6%, p &lt; 0.001). By multivariable analysis, the presence of &gt;1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p &lt; 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Psychopathological and Interactive-Relational Characteristics in Non-Suicidal Self-Injury Adolescent Outpatients

Non-suicidal self-injury (NSSI) is described as behaviors that directly and intentionally inflict damage to body tissue without suicidal intent and for reasons not linked to cultural expectations or norms. Literature has confirmed several “specific risk factors” related to NSSI behaviors; emotional reactivity, internalizing problems, alexithymia traits, and maladaptive family functioning can predispose an individual to intrapersonal and interpersonal vulnerabilities related to difficulties in regulating one’s own cognitive-emotional experience. The present study aims to analyze and define the psychopathological and family interactive-relational characteristics of adolescents with NSSI through a case-control study. Thirty-one patients with NSSI and thirty-one patients without NSSI paired for sex, age, and psychiatric diagnosis (ICD-10) were recruited in Padua among two Child Neuropsychiatry Units before the COVID-19 pandemic. Results show a higher prevalence of internalizing problems, alexithymia trait related to “difficulty identifying feelings”, and lower quality of family functioning related to inclusion of partners, child involvement, and child self-regulation. These results carry significant implications for the clinical management and therapeutic care of non-suicidal self-injury patients and further confirm the need for an in-depth investigation of internalizing problems, alexithymia, and quality of family interactions

Psychopathological and Interactive-Relational Characteristics in Non-Suicidal Self-Injury Adolescent Outpatients

Non-suicidal self-injury (NSSI) is described as behaviors that directly and intentionally inflict damage to body tissue without suicidal intent and for reasons not linked to cultural expectations or norms. Literature has confirmed several &ldquo;specific risk factors&rdquo; related to NSSI behaviors; emotional reactivity, internalizing problems, alexithymia traits, and maladaptive family functioning can predispose an individual to intrapersonal and interpersonal vulnerabilities related to difficulties in regulating one&rsquo;s own cognitive-emotional experience. The present study aims to analyze and define the psychopathological and family interactive-relational characteristics of adolescents with NSSI through a case-control study. Thirty-one patients with NSSI and thirty-one patients without NSSI paired for sex, age, and psychiatric diagnosis (ICD-10) were recruited in Padua among two Child Neuropsychiatry Units before the COVID-19 pandemic. Results show a higher prevalence of internalizing problems, alexithymia trait related to &ldquo;difficulty identifying feelings&rdquo;, and lower quality of family functioning related to inclusion of partners, child involvement, and child self-regulation. These results carry significant implications for the clinical management and therapeutic care of non-suicidal self-injury patients and further confirm the need for an in-depth investigation of internalizing problems, alexithymia, and quality of family interactions

Alexithymia and Psychopathological Manifestations Centered on the Body: Somatization and Self-Harm

The present study aimed to investigate alexithymia and psychopathological manifestations centered on the body in a sample of adolescents with somatizing and/or self-harming issues to analyze the phenomenon of NSSI linked to Somatic Symptom Disorders (SSD). A sample of 184 adolescents between 12 and 19 years of age, was divided into three groups, one with NSSI (n = 49) and the second group with SSD (n = 57), comparing them with a third group of adolescents with SSD and NSSI (n = 78) to investigate their differences and similarities in psychopathological correlates and to analyze the mediation role of alexithymia and emotional dysregulation in NSSI and SSD related to internalizing problems. The battery of tests included the Toronto Alexithymia Scale (TAS-20) and the Youth Self-Report 11&ndash;18 (YSR). The NSSI + SSD group scored higher than the other two groups on all the YSR scales. The affective syndromes were the only clinical condition that discriminated between the three groups. On all the other syndrome scales, the NSSI + SSD group differed from the other two groups, while there were no differences between the NSSI group and the SSD group. The NSSI + SSD group revealed a more severely deficient emotional self-regulation. Difficulty identifying feelings was a trait shared by adolescents with SSD and those engaging in NSSI, a more complex overall alexithymia profile was associated with the combination of self-harming behavior and somatization. Alexithymia and emotional dysregulation played a mediating role in the relationship between internalizing problems and somatization. We did not find a mediating role in alexithymia and emotional dysregulation in the relationship between internalizing problems and self-injurious behavior. The combination of NSSI and SSD gave rise to more severe psychopathological correlates, clinical levels of alexithymia, and more severe deficient emotional self-regulation. Results of mediation role indicated a link between alexithymia, emotional dysregulation, and somatization