COVID-19: The Development and Validation of a New Mortality Risk Score.

Background: The coronavirus disease 2019 (COVID-19) pandemic has found the whole world unprepared for its correct management. Italy was the first European country to experience the spread of the SARS-CoV-2 virus at the end of February 2020. As a result of hospital overcrowding, the quality of care delivered was not always optimal. A substantial number of patients admitted to non-ICU units could have been treated at home. It would have been extremely useful to have a score that, based on personal and clinical characteristics and simple blood tests, could have predicted with sufficient reliability the probability that a patient had or did not have a disease that could have led to their death. This study aims to develop a scoring system to identify which patients with COVID-19 are at high mortality risk upon hospital admission, to expedite and enhance clinical decision making. Methods: A retrospective analysis was performed to develop a multivariable prognostic prediction model. Results: Derivation and external validation cohorts were obtained from two Italian University Hospital databases, including 388 (10.31% deceased) and 1357 (7.68% deceased) patients with confirmed COVID-19, respectively. A multivariable logistic model was used to select seven variables associated with in-hospital death (age, baseline oxygen saturation, hemoglobin value, white blood cell count, percentage of neutrophils, platelet count, and creatinine value). Calibration and discrimination were satisfactory with a cumulative AUC for prediction mortality of 0.924 (95% CI: 0.893-0.944) in derivation cohorts and 0.808 (95% CI: 0.886-0.828) in external validation cohorts. The risk score obtained was compared with the ISARIC 4C Mortality Score, and with all the other most important scores considered so far, to evaluate the risk of death of patients with COVID-19. It performed better than all the above scores to evaluate the predictability of dying. Its sensitivity, specificity, and AUC were higher than the other COVID-19 scoring systems when the latter were calculated for the 388 patients in our derivation cohort. Conclusions: In conclusion, the CZ-COVID-19 Score may help all physicians by identifying those COVID-19 patients who require more attention to provide better therapeutic regimens or, on the contrary, by identifying those patients for whom hospitalization is not necessary and who could therefore be sent home without overcrowding healthcare facilities. We developed and validated a new risk score based on seven variables for upon-hospital admission of COVID-19 patients. It is very simple to calculate and performs better than all the other similar scores to evaluate the predictability of dying.

Food Beliefs and the Risk of Orthorexia in Patients with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) believe that diet plays a significant role in the pathogenesis of their disease and the exacerbation of their symptoms. They often adopt restrictive diets that can lead to malnutrition, anxiety, and stress. Recent studies have found a correlation between IBD and eating disorders, such as anorexia nervosa and ARFID (Avoidant Restrictive Food Intake Disorder). None of these studies report an association with orthorexia nervosa, which is an obsession with healthy and natural foods. The aim of this study was to assess the risk of orthorexia nervosa in patients with IBD. A total of 158 consecutive subjects were recruited, including 113 patients with IBD and 45 controls. The standardized Donini questionnaire ORTO-15 was administered to assess the risk of orthorexia, and clinical and demographic data were collected. The results showed that patients with IBD had a risk of developing orthorexia nervosa of 77%. This was significantly higher than the 47% observed in the control group. In the patients with IBD, the risk of orthorexia was associated with a lower BMI, at least in patients older than 30 years, and it was also associated with marital status in patients younger than 30. In conclusion, many patients with IBD are at increased risk of developing orthorexia nervosa, which may have a negative impact on their psychological wellbeing and social sphere, expose them to a high risk of nutritional deficiencies, and affect their overall quality of life. Further high-quality studies are needed to assess the clinical impact of orthorexia and its correlation with clinical features and classified eating disorders.

Ultrasound Parameters Can Accurately Predict the Risk of Malignancy in Patients with "Indeterminate TIR3b" Cytology Nodules: A Prospective Study.

The increase in the incidence of thyroid nodules with cytological findings of TIR3b requires the identification of predictive factors of malignancy. We prospectively evaluated 2160 patients from January 2018 to June 2022 and enrolled 103 patients with indeterminate cytology TIR3b nodules who underwent total (73 patients) and hemi-thyroidectomy (30 patients). Among them, 61 had a histological diagnosis of malignancy (30 classic papillary thyroid carcinoma, 19 had follicular papillary thyroid carcinoma variant, 3 had Hurtle cell carcinoma and 9 had follicular thyroid carcinoma), while 42 had a benign histology. Clinical, ultrasonographic and cytological characteristics were recorded. In addition, BRAF mutation was analysed. Patients with a histological diagnosis of malignancy had a higher frequency of nodule diameter ≤11 mm (p = 0.002), hypoechogenicity (p < 0.001), irregular borders (p < 0.001), peri- and intralesional vascular flows (p = 0.004) and microcalcifications (p = 0.001) compared to patients with benign histology. In contrast, patients with benign histology had more frequent nodules with a halo sign (p = 0.012) compared to patients with histological diagnosis of malignancy. No significant differences were found in BRAF mutation between the two groups. Our study suggests that the combination of ultrasonographic and cytological data could be more accurate and reliable than cytology alone in identifying those patients with TIR3b cytology and a histology of malignancy to be referred for thyroidectomy, thus reducing the number of patients undergoing thyroidectomy for benign thyroid disease.

Evidence of greater severity of diabetic foot ulcers during COVID-19 pandemic: A real-life single-centre cohort study.

AIMS: In the Sars-Cov-2 pandemic era, patients with diabetes mellitus (DM) manifested more severe forms of Sars-Cov-2 with greater mortality than non-diabetic patients. Several studies documented more aggressive forms of diabetic foot ulcers (DFU) during the pandemic period even though the results were not unanimously confirmed. The aim of this study was to evaluate the clinical-demographic differences between a cohort of Sicilian diabetic patients hospitalised for DFU in the pre-pandemic 3 years and a cohort of patients hospitalised in the pandemic 2 years. MATERIALS AND METHODS: One hundred and eleven patients from the pre-pandemic period 2017-2019 (Group A) and 86 patients from the pandemic period 2020-2021 (Group B) with DFU, admitted to the division of Endocrinology and Metabolism of the University Hospital of Palermo, were retrospectively evaluated. The clinical assessment of the type, staging and grading of the lesion, and the infective complication from DFU was performed. RESULTS: No differences in HbA1c values were observed between the two groups. Group B showed a significantly higher prevalence of male subjects (p = 0.010), neuro-ischaemic ulcers (p < 0.001), deep ulcers with involvement of bones (p < 0.001), white blood count levels (p < 0.001), and reactive C protein (p = 0.001) compared to group A. CONCLUSIONS: Our data show that in the COVID-19 pandemic, a greater severity of ulcers requiring a significantly greater number of revascularisations and more expensive therapy, but without an increase in the amputation rate, was observed. These data provide novel information on the impact of the pandemic on diabetic foot ulcer risk and progression.

N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A Comprehensive Review.

Aims: N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment. Methods: Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). Results: In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The mortality rate across different studies ranged from 0 to 52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100-150 mg/kg) and oral (70-140 mg/kg), and length of treatment varied-12, 24, or 48 h for I.V. regimen and 72 h for oral administration. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality; if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one. Conclusion: NAC improves hepatotoxicity and reduces mortality. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients.

Diabetic foot ulcers: Retrospective comparative analysis from Sicily between two eras.

AIM: The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008-2013 and 2014-2019. METHODS: We compared the two eras, era1: 2008-13, era2: 2014-19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled. RESULTS: In the population hospitalized for DFU in 2008-2013, 59.1% of males and 40.9% of females died, whilst in 2014-2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p < 0.001), just as CKD was severe (14.5% vs. 4%, p < 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07-2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37-2.95, p <0.001) and eGFR less than 92 ml/min (OR 2.84, 95% CI 1.51-5.34, p 0.001) were independently associated with risk of death. CONCLUSIONS: Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality.

Predictive factors of polycystic ovary syndrome in girls with precocious pubarche.

OBJECTIVE: The aim of this study is to clarify, in girls with premature pubarche (PP), the influence of premature androgenization on the prevalence of polycystic ovary syndrome (PCOS). DESIGN AND PATIENTS: Ninety-nine PP girls, 63 who developed PCOS and 36 who did not develop PCOS, were retrospectively included. Clinical, anthropometric, and metabolic parameters were evaluated at the time of diagnosis of PP and after 10 years from menarche to find predictive factors of PCOS. RESULTS: Young females with PP showed a PCOS prevalence of 64% and showed a higher prevalence of familial history of diabetes (P = 0.004) and a lower prevalence of underweight (P = 0.025) than PP-NO-PCOS. In addition, girls with PP-PCOS showed higher BMI (P < 0.001), waist circumference (P < 0.001), total testosterone (P = 0.026), visceral adiposity index (VAI) (P = 0.013), total cholesterol (P < 0.001), LDL-cholesterol (P < 0.001), non-HDL cholesterol (P < 0.001) and lower age of menarche (P = 0.015), ISI-Matsuda (P < 0.001), DIo (P = 0.002), HDL cholesterol (P = 0.026) than PP-NO-PCOS. Multivariate analysis showed that WC (P = 0.049), ISI-Matsuda (P < 0.001), oral disposition index (DIo) (P < 0.001), VAI (P < 0.001), total testosterone (P < 0.001) and LDL-cholesterol (P < 0.001) are independent predictive factors for PCOS in girls with PP. CONCLUSIONS: Our study established a strong association between multiple risk factors and development of PCOS in PP girls. These risk factors are predominantly related to the regulation of glucose, lipid, and androgen metabolism. Among these factors, WC, ISI-Matsuda, DIo, VAI, total testosterone, and LDL-cholesterol predict PCOS.

Perception of the Role of Food and Dietary Modifications in Patients with Inflammatory Bowel Disease: Impact on Lifestyle.

BACKGROUND: Diet has a relevant role in triggering symptoms in inflammatory bowel disease (IBD) from the patients' perspective, but there is gap the between patients' and doctors' perceptions. Few studies have addressed this topic. The aim of this study was to evaluate food habits and nutrition knowledge in a homogeneous cohort of patients with IBD from southern Italy. METHODS: 167 consecutive patients with IBD were recruited. The survey was based on the administration of a semi-structured questionnaire assessing demographics, disease features, dietary behavior, and food intolerance. RESULTS: The majority of patients did not consider food a cause of their disease. However more than 80% changed their diet after the diagnosis and most report an improvement in symptoms. Spiced and seasoned foods, dairy products, vegetables, and fruit were often avoided. A dairy-free diet was adopted by 33.7%. Food choices were based on self-experience and not on medical counselling. Dietary modifications deeply impact on lifestyle. CONCLUSIONS: Most of the patients with IBD set diet and lifestyle on self-experience and give up many foods. This has an impact on psychosocial functioning and can lead to nutritional deficiencies. High quality studies are warranted to assess evidence-based dietary strategies and develop patient-targeted dietary recommendations.

Recurrent sacrococcygeal pilonidal disease: the efficacy of minimal subcutaneous excision of the sinus and unroofing of pseudocystic cavity.

Patients undergoing surgery for recurrent pilonidal disease are at high risk of developing re-recurrence. The present prospective analysis was performed to evaluate the outcome for recurrent pilonidal disease treatment with a technique that provides a minimal subcutaneous excision of fistula and of the skin above the cyst, with secondary healing of wounds. METHODS: 48 consecutive patients with previous surgical excision and recurrent pilonidal disease underwent surgery from January 2009 to December 2016, under local anaesthesia. The age of the patients (42 males and 6 females) at the time of our observation was 28.5 ± 10.2 years, the BMI of 26.3 ± 6.8. The average number of interventions prior to our was 2.02 ± 1.14. RESULTS: The mean operative time was 18.2 ± 5.5 minutes. All patients were discharged 2 to 4 hours after surgery, with an average healing time of 22.8 ± 15.3 days. We recorded, in the follow-up period, only 4 relapses (8.32%), all retreated with the same surgical procedure and brought to complete healing. The results of the cosmetic questionnaire, which assessed patient satisfaction and contentment, showed that 96% of patients were completely satisfied and all patients recommended surgery to others. Kaplan-Meier analysis showed that in 7 years of follow-up, 85% of patients healed without recurrence. CONCLUSIONS: Our simple procedure appears to be safe and easily reproducible, allowing a high surgical success in the treatment of recurrent pilonidal disease. KEY EORDS: Excision, Healing, Recurrent sacrococcygeal pilonidal disease.

The association between education level and chronic liver disease of any etiology.

BACKGROUND: The potential link between educational level and chronic liver diseases (CLD) were explored using the mortality records of liver cirrhosis, which lack accuracy and are unable to identify the different etiological factors of liver cirrhosis. Information on the association of low educational level with the severity of CLD is lacking. AIM: To evaluate the potential association linking education level to etiology and clinical stage of CLD cases. METHODS: Consecutive enrolment of 11,107 subjects with CLD aged≥18 years prospectively recruited in two national surveys in 2001 and 2014 at one of the participating Italian liver units throughout the country. Subjects were pooled in two groups: low education level (less than high school) and high education level (completed high school or beyond). The association of demographic, etiological, and clinical stage of subjects with educational level was assessed using logistic regression analysis. In the analysis low educational level was the outcome variable. RESULTS: A total of 11,107 subjects born in Italy (mean age 55.5 years, sex ratio 1.5) were evaluated. Multiple logistic regression analysis shows that chronic HCV infection (O.R.1,38:95%,C.I.1.23-1.55), risky alcohol intake (O.R.1.96;95%,C.I.1.73-2.21) and liver cirrhosis (O.R.1.65;95%,C.I.1.46-1.85) all resulted independently associated with less than a completed high school education. HBV infection resulted independently associated with high education level (O.R.0.74;95%,C.I.0.64-0.86), reflecting changes in HBV modes of transmission in recent decades. No association was found with CLD related to non-alcoholic fatty liver disease (O.R.1.03;95%, C.I.0.81-1.30). CONCLUSIONS: These findings show an independent association linking education level with viruses and alcohol-related CLD. Low educational level is associated with the severity of CLD.

Umbilical hernioplasty in cirrhotic patients with ascites A case control study.

OBJECTIVE: Umbilical hernia is a very frequent pathology, and plastic with prosthetic material is the most frequently used surgical procedure currently used for its repair. In patients with cirrhosis in asciic phase, this pathology is particularly frequent, with a tendency to rapidly increase in size and to become symptomatic. In the past treatment with traditional surgery in cirrhotic patients was considered problematic and was viewed with reserve, and only recently is the surgical approach recommended also in these patients. This study is aimed to evaluate the feasibility and safety of open umbilical hernia plastic with prosthetic material in cirrhotic and ascitic patients. MATERIALS AND METHODS: Our case-control study was conducted on 35 male patients with ascitic phase liver cirrhosis and an equal number of non-cirrhotic patients, all suffering from uncomplicated but symptomatic umbilical hernia, treated surgically consecutively from March 2005 to March 2015. All patients underwent open umbilical hernioplasty with placement of a retromuscular pre-aponeurotic mesh. RESULTS: Of the 35 patients with liver cirrhosis, 20% were classified in Class C, according to Child-Pugh, 28.5% had a MELD score> 15. We have not shown any post-operative mortality. In general, minor complications were observed, more frequent in cirrhotic patients than in healthy controls (p = 0.0315). Among the aforementioned complications the most frequent were hematomas and wound infections, more frequent in cirrhotic patients in Class C according to Child- Pugh and with MELD score> 15 (p <0.005). CONCLUSIONS: Our study shows that umbilical hernia pathology in ascitic cirrhotic patients can be treated surgically with satisfactory results especially in Child-Pugh class A and B patients. The surgical approach of choice must, preferably, be the preferred prosthetic plastic after pre-operative optimization of the coagulation, nutritional and ascitic state. KEY WORDS: Ascites, Hernioplasty ,Liver cirrhosis; Umbilical hernia.

Inguinal hernioplasty in patients with cirrhosis and ascites: what preventive measures are needed for a safe procedure?

BACKGROUND: Inguinal hernioplasty in patients with LC and ascites has been long discouraged for the incidence of postoperative complications. The aim is to evaluate the appropriateness of this elective surgical procedure in patients with LC and ascites. METHODS: Thirty consecutive LC patients with ascites and affected by inguinal hernia (LC group), who underwent elective open inguinal hernioplasty with mesh placement, have been matched with the same number of patients non-LC (non-LC group) who underwent the same surgical procedure in the same period of time. All patients in LC group received a careful hepatological assessment and were classified according to the etiology of LC and to the Child's class. Patients of both groups received an antibiotic prophylaxis and were operated under local anesthesia. RESULTS: No significant complications were observed in any patients during surgery. The hospital stay was significantly longer in LC group. During the postoperative time, 4 inguinoscrotal hematoma appeared in LC group, of which 3 in class C (LC VS non-LC p>0.05; non-LC VS Child's class C p<0.023). Ascites leakage or wound infection were not observed. CONCLUSION: Inguinal hernioplasty can be safely performed for LC patients in Child's class A and B; for patients in class C, careful attention must be paid to the hemorrhagic events. KEY WORDS: Ascites, Cirrhosis, Hernioplasty.

Decreasing role of HCV and HBV infections as aetiological factors of hepatocellular carcinoma in Italy.

BACKGROUND: The epidemiology of hepatocellular carcinoma (HCC) is characterized by a dynamical temporal trend of well-established and emerging risk factors. METHODS: We evaluated the temporal trend of aetiological factors of HCC over the last two decades in Italy. HCC cases were recruited from two previously published national studies in 1996 and in 2008 and HCC cases were also enlisted from two national surveys in 2001 and in 2014 enrolling consecutive subjects with chronic liver disease (CLD) referring to more than 80 liver units scattered all over the country for a 6-month period. RESULTS: Out of the 9997 subjects with CLD recruited in 2001 and the 2408 recruited in 2014, 3.3% and 5.7% (P < 0.001), respectively, had HCC. The temporal trend of HBsAg -/HCV + HCC cases significantly linearly decreased from 71.1% in 1996 to 57.2% in 2014 (P < 0.001). Conversely, that of virus-negative cases significantly linearly increased from 12.1% to 28.3% (P < 0.001). The proportion of HBV-related HCC cases showed a steady low rate, reflecting the reduced endemicity of the infection in Italy. The proportion of HCC with compensated cirrhosis (i.e., Child-Pugh A) linearly increased over time from 55.6% in 1996 to 76.0% in 2014 (P < 0.001) reflecting the growing effectiveness of semi-annual ultrasound surveillance for early detection of HCC. CONCLUSION: In conclusion, with decreasing viral aetiology, an overall decrease in the incidence of HCC might be expected in the future. The proportion of metabolic diseases is conversely increasing being considered as an aetiology. The growing prevalence of metabolic disorders in the general population may further increase this trend in the years to come.

Geographical pattern of chronic liver diseases in Italy: Results from two pooled national surveys.

BACKGROUND: The information on the geographical characteristics of chronic liver diseases (CLD) in Italy is out-dated. AIM: To provide up-dated information on the geographical pattern of patients with CLD born in Italy. METHODS: Patients with CLD were enrolled in two national surveys performed in 2001 and 2014, which prospectively recruited subjects aged ≥18 years referring to Italian liver units located throughout the country that apply a similar clinical approach and analytical methods. RESULTS: The total number of patients enrolled was 11,676. Alcohol-related CLD was more frequently observed in northern/central areas (25.0% vs. 20.7%, p < .001), while HBV-related (15.4% vs. 13.3%, p = .02) and HCV-related (71.2% vs. 67.1%, p < .001) CLD prevailed in southern areas/main islands (Sicily and Sardinia). These differences were stable over time. Liver cirrhosis without HCC was diagnosed more frequently in southern area/islands than in northern/central areas (23.7% vs. 18.8%, p < .01). Moreover, an increased proportion over time of patients with cirrhosis without HCC was observed both in northern/central areas (17.3% vs. 27.4%, p < .01) and in southern area/islands (22.6% vs. 27.9%, p < .01). CONCLUSIONS: These up-dated findings show different geographical patterns of CLD in Italy, reflecting different behavioural habits and socio-economic conditions across the country. They may be useful to apply more adequate preventive measures and to allocate economic resources.

The burden of HBV infection in HCV patients in Italy and the risk of reactivation under DAA therapy.

BACKGROUND: There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs). AIM: To provide figures on the prevalence of HBV markers in HCV-RNA-positive subjects in Italy, where these findings are lacking. METHODS: All subjects aged ≥18 years with CLD consecutively referring to Italian liver units located throughout country were prospectively enrolled in two national surveys in 2001 and 2014. RESULTS: The total number of HCV-RNA-positive cases was 6984; 356 (5.1%) subjects vaccinated against HBV were excluded. A total of 6628 cases were evaluated. The prevalence rates of HBsAg, isolated anti-HBc and anti-HBc/anti-HBs-positivity were 2.9%, 8.1% and 14.7%, respectively. Among the estimated one million HCV-RNA-positive subjects in Italy, a substantial number of subjects are at risk of HBV reactivation due to DAA therapy. The prevalence of liver cirrhosis was higher than that of CLD in HBsAg-positive subjects (4.4% vs. 2.6%, p < 0.01) but not in those positive for other HBV markers. CONCLUSIONS: These findings outline the burden of HBV markers among HCV-RNA-positive subjects in Italy, where in 2017 reimbursement for DAA therapy by the National Health System became universal for all patients with chronic HCV infection. HBV vaccination coverage should be greatly extended, since nearly two thirds of subjects in this study resulted negative for any HBV marker.

Characteristics and Changes over Time of Alcohol-Related Chronic Liver Diseases in Italy.

Introduction: To evaluate the characteristics of alcohol-related chronic liver disease (CLD) in Italy and their potential changes over time. Patients and Methods: Subjects with CLD were enrolled in two national surveys performed in 2001 and in 2014 in Italy. The two surveys prospectively recruited patients aged ≥ 18 years referring to more than 80 Italian liver units scattered all over the country using similar clinical approach, analytical methods, and threshold of risky alcohol intake definition (≥ 3 units/day in men and ≥ 2 units/day in women). Results: Out of 12,256 enrolled subjects, 2,717 (22.2%) reported a risky alcohol intake. Of them, anti-HCV positive was observed in 48.3% of subjects. The overall sex ratio (M/F) was 3.1, decreasing from 3.8 in 2001 to 1.3 in 2014. Women were significantly older than men (58.9 versus 53.1 years; p < 0.01) and an increasing ageing over time was observed in both sexes. The proportion of subjects with liver cirrhosis increased over time in both sexes, and decompensated stage (Child B or C) was detected in 55.9% of cases in 2001 and 46.0% in 2014. Conclusions: Risky alcohol intake plays a role in more than one-fifth of CLD in Italy, with a shift over time towards an older age and a more severe liver disease stage. These data put alcohol back in the spotlight with an important role in CLD in the years to come in Italy.

Necrotizing Soft Tissue Fasciitis after Intramuscular Injection.

Necrotizing soft tissue fasciitis (NSTIs) or necrotizing fasciitis is an infrequent and serious infection. Herein, we describe the clinical course of a female patient who received a diagnosis of NSTIs after gluteus intramuscular injection. We also report the results of our review of published papers from 1997 to 2017. Since now, 19 cases of NSTIs following intramuscular injections have been described. We focus on the correlation between intramuscular injection and NSTIs onset, especially in immunosuppressed patients treated with corticosteroids, suffering from chronic diseases or drug addicted. Intramuscular injections can provoke severe tissue trauma, representing local portal of infection, even if correctly administrated. Otherwise, it is important not to inject drug in subcutaneous, which is a less vascularized area and therefore more susceptible to infections. Likewise, a proper injecting technique and aspiration prior to injection seem to be valid measure to prevent intra-arterial or para-arterial drug injection with the consequent massive inflammatory reaction. Necrosis at the infection site appears to be independent of the drug, and it is a strong additional risk factor for NSTIs.

Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy.

BACKGROUND: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014). METHODS: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods. RESULTS: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (p < 0.001) and with a higher rate of cirrhosis and/or HCC (p < 0.001) than those investigated in 2001. There was a remarkable increase over time in the proportion of male abstainers (36.7% in 2001 and 64.3% in 2014). CONCLUSION: This study highlights important inter- and intra-gender differences in the characteristics and etiological factors of patients with CLD in Italy.

Anti-tumour necrosis factor-α antibodies and B cell homeostasis in human inflammatory bowel diseases.

BACKGROUND: The expression of CD70 on T cells is greatly enhanced by antigen-presenting cell (APC)-associated signals, such as tumour necrosis factor(TNF)-α, which is constitutionally high in patients with inflammatory bowel disease (IBD). Experimentally, the chronic activation of CD27 as a result of the constitutive expression of CD70 leads to the demise of B cells in bone marrow (BM) and the secondary lymphoid organs. The aim of this study was to assess the number and phenotype of circulating B cell in untreated IBD patients and their counterparts treated with biological anti-TNF drugs. METHODS: The study involved 13 untreated IBD patients, 36 IBD patients treated with biological drugs, and 10 healthy controls. The B cell phenotypes were assessed by means of flow cytometry using monoclonal antibodies specific for CD20, CD19, CD3, CD27 and CD43. In order to evaluate B cell development in bone marrow and peripheral B cell activation, we identified four B cell subsets: hematogones (HBs: CD20+19+3-27-43+), memory B cells (MBs: CD20+19+3-27+43-), pre-plasmablasts (PPBs: CD20+19+3-27+43+), and plasmablasts (PBs: CD20-19+3-27+43+). RESULTS: The total number of B cells in the untreated patients was three times lower than that in the patients treated with biological drug (p<0.001), and half that in the healthy controls (p=0.03). The between-group differences (including the healthy donors) were statistically significant in the case of HBs and MBs, but not in the case of PPBs and PBs. Only one treated patient showed a transiently large increase in PPBs. There were statistically significant differences in all of the parameters between the untreated patients and those receiving biological therapy, and in some cases between the untreated patients and healthy controls, but never between the controls and the treated patients. Four non-responders to anti-TNF therapy had a smaller number of total circulating B cells than the untreated patients. CONCLUSIONS: Anti-TNF drugs disinhibit B cell production in IBD patients, but maintain the constant homeostasis of circulating B cells. The presence of individual variations may allow the activity of anti-TNF drugs to be monitored by studying B cell subgroups.

Sex difference in the interaction of alcohol intake, hepatitis B virus, and hepatitis C virus on the risk of cirrhosis.

BACKGROUND: The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation. OBJECTIVE: Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis. DESIGN: We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis. RESULTS: Females were older than males (p<0.01) and less frequently showed HBV and alcoholic aetiology (p<0.01). In both sexes, an overtime increasing age and an increasing proportion of subjects with liver cirrhosis was observed, reflecting a better survival (0.01). An additive interaction is observed in females: the O.R. generated by the simultaneous presence of HBV, HCV, and alcohol (5.09; 95% C.I. 1.06-24.56) exceeds the sum (4.14) of the O.R. generated by a single exposure (O.R. = 0.72 for HBsAg positivity, OR = 1.34 for anti-HCV positivity, and O.R. = 2.08 for alcohol intake). No interaction is observed in male sex. CONCLUSIONS: The observed gender difference suggests that the simultaneous presence of HBV/HCV coinfection and risky alcohol intake enhances the mechanism of liver damage to a greater extent in females than in males.