Hemorrhagic emergency due to esophagogastric varices in the portal hypertension patient

High gastrointestinal hemorrhage represents the more frequent (12-71.1%) and heavy complication of hepatic cirrhosis and correlates to portal hypertension; it is weighed by global mortality which sways from 30 to 50%. High gastrointestinal hemorrhage gives, therefore, a serious of diagnostic and therapeutic problems not easy to guide for at least 3 reasons: numerous causes of bleeding; hepatic failure; the marigold possible therapies. Aim of this work is to clarify some diagnostic and therapeutic features about high gastrointestinal hemorrhage in cirrhotic patient, because such eventuality often presents dramatic aspects, which endangers the patient's life. Our experience shows a casuistry referred to the period of time which goes from 1987 to 1998 and that comprehend 143 examined patients: 91 of them have been submitted to medical treatment (endoscopic sclerotherapy, glupressin e/o somatostatin); in 52 cases it has been possible to realize a surgical treatment, different from the elective therapy (33 pz) and emergency therapy. Immediate hemostatic effect obtained in both the conditions, has been satisfying with best results at a distance of three years and five years given by devascularization. As matter stands our preference of the devascularization surgical treatment, it seems appropriate to pay attention to the operation of mesocaval anastomosis which, either in our very brief experience (3 cases) or by international literature, seems to offer encouraging results.     

From target identification to drug screening assays for neurodegenerative diseases.

Treatment of neurodegenerative diseases represents a major challenge for the pharmaceutical industry. Key to developing novel and efficacious therapeutics is the discovery of new druggable targets. Toward this aim, the current drug discovery process is strongly relying on the improved understanding of disease mechanisms and on a synergistic approach with chemistry, molecular biology and robotics. In this scenario, we present the case of a newly discovered molecular mechanism that may be of interest for drug discovery programmes in Huntington's disease and other neurodegenerative diseases.     

Impaired Vagal Activity in Long-COVID-19 Patients

Long-COVID-19 refers to the signs and symptoms that continue or develop after the “acute COVID-19” phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized β-coefficient = 0.259), NT-ProBNP (standardized β-coefficient = 0.281), HF component of spectral analysis (standardized β-coefficient = 0.696), and LF/HF ratio (standardized β-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.     

Osseointegrated Metallic Implants for Finger Amputees: A Review of the Literature

Digital trauma amputations and digital agenesis strongly affect the functionality and aesthetic appearance of the hand. Autologous reconstruction is the gold standard of treatment. Unfortunately, microsurgical options and transplantation procedures are not possible for patients who present contraindications or refuse to undergo transplantation from the toe (e.g. toe‐to‐thumb transplantation). To address these issues, osseointegrated finger prostheses are a promising alternative. The functional assessments registered during follow‐up confirmed the promising outcomes of osseointegrated prostheses in the treatment of hand finger amputees. This review outlines (a) a detailed analysis of osseointegrated finger metallic components of the implants, (b) the surgical procedures suggested in the literature, and (c) the functional assessments and promising outcomes that demonstrate the potential of these medical osseointegrated devices in the treatment of finger amputees.     

Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients

Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.     

Niosomes as carriers for tretinoin. II. Influence of vesicular incorporation on tretinoin photostability

In this work, we compared the chemical stability of tretinoin (TRA) in methanol and in vesicular suspensions exposed both to UV and artificial daylight conditions with the aim of evaluating the potential of niosomes as topical carriers capable of improving the stability of photosensitive drugs. Tretinoin-loaded niosomes were prepared from polyoxyethylene (4) lauryl ether (Brij^® 30), sorbitan esters (Span^® 40 and Span^®60) and a commercial mixture of octyl/decyl polyglucosides (Triton^® CG110). Liposomes made from hydrogenated (P90H) and non-hydrogenated (P90) soy phosphatidylcholines were also prepared and studied. In order to evaluate the influence of vesicle structure on the photostability of tretinoin, TRA-loaded vesicles were prepared by the film hydration method, extrusion technique and sonication. After UV irradiation, TRA dissolved in methanol degraded very quickly while the incorporation in vesicles always led to a reduction of the photodegradation process. The photoprotection offered by vesicles varied depending on the vesicle structure and composition. After fluorescent light irradiation for 21 days, not all the studied vesicular formulations improved TRA stability when compared with the free drug in methanol. Tretinoin incorporated in P90 or Span vesicles presented a half-life shorter or very close to that of the free drug. However, the inclusion of TRA in P90H liposomes and Brij^® 30 or Triton^® CG110 niosomes retarded the drug photodegradation.     

Metronidazole-induced hepatotoxicity in a patient with xeroderma pigmentosum: A case report

Rationale:Whereas metronidazole-induced hepatotoxicity is quite rare in the general population, in individuals carrying a nucleotide excision repair disorder, namely Cockayne syndrome, there is a high risk of developing this complication.Patient concerns:We report the case of a 44-year-old man, affected by xeroderma pigmentosum, who was admitted to the hospital presenting aspiration pneumoniae caused by worsening dysphagia and with severe hepatotoxicity during the hospitalization.Diagnoses:Acute hepatitis, which was leading to acute liver failure, occurred during antibiotic treatment with metronidazole and ceftazidime with an elevation of liver enzymes consistent with hepatocellular damage pattern.Interventions:Hydration with glucose 5% solution, pantoprazole and vitamin K were administered, meanwhile other causes of hepatitis were ruled out and the ongoing antibiotic treatment was stopped suspecting a drug-induced liver injury.Outcomes:Liver function nearly completely recovered 1 month later with a first rapid improvement, within few days, of aminotransferases and coagulation studies, and slower of cholestatic enzymes.Lessons:We describe the first case available in the literature of hepatotoxicity associated with metronidazole treatment in a xeroderma pigmentosum patient. Clinicians therefore, based on this report and according to the possible underlying mechanism shared by other genetic diseases characterized by alterations in the pathway of DNA-repair, should consider such adverse event also in patients affected by this rare disease.     

SARS-CoV-2 Specific Immune Response and Inflammatory Profile in Advanced HIV-Infected Persons during a COVID-19 Outbreak

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann–Whitney or Kruskal–Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53–62); 76% male; median HIV duration of infection, 18 years (15–29); nadir of CD4, 57/mmc (23–100) current CD4 count, 348/mmc (186–565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination.     

Metformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer

IntroductionDiabetic patients treated with metformin have a lower risk of developing BC or a better BC prognosis. Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin. In a randomized study on nondiabetic BC patients in natural menopause with high testosterone levels, we observed a significant decrease in insulin and in testosterone levels with metformin 1500 mg/d compared with 1000 mg/d. We present the results of a new analysis of our study on the effect of metformin on the bioavailability of sex hormones.Patients and MethodsOne hundred twenty-four eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months continued the study using 1000 mg/d for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose to 1500 mg/d, and the other group continued with 1000 mg/d.ResultsNinety-six women completed the study, 43 receiving metformin 1500 mg/day, and 53 receiving 1000 mg/day. The women receiving 1500 mg/d showed a greater and significant reduction of free testosterone (?29%) and estradiol (?38%), a borderline significant reduction of estrone and insulin-like growth factor-1, and a nonsignificant reduction of androstenedione. They also showed a nonsignificant increase of dehydroepiandrosterone sulfate.ConclusionMetformin does not interfere with the production of dehydroepiandrosterone sulfate. Besides, it decreases estradiol levels, basically through the reduction of testosterone. These hormonal changes might have clinical relevance.     

The role of apical vaginal support in the appearance of anterior and posterior vaginal prolapse

OBJECTIVE: To describe how simulated apical support affects the appearance of prolapse in the anterior and posterior vagina using a modification of the Pelvic Organ Prolapse Quantification (POP-Q) examination. METHODS: Women with prolapse stage II or greater were examined using the POP-Q. To simulate apical support, the posterior blade of a standard Graves speculum was positioned over the posterior vagina to support the vaginal apex while remeasuring points Aa and Ba and over the anterior vagina to support the apex while remeasuring points Ap and Bp. Change in anterior and posterior POP-Q points and prolapse stage with apical support were calculated. RESULTS: One hundred ninety-seven women were enrolled with mean age of 62+/-14 years, median parity of 2 (range 0-8), and mean body mass index of 28+/-5 kg/m(2). By standard POP-Q, 36% had stage II prolapse, 54% had stage III, and 10% had stage IV prolapse. With simulated apical support, point Ba changed to stage 0 or I in 55% of cases and point Bp changed to stage 0 or I in 30% (P<.001 for each point). Mean change for point Ba with apical support was 3.5+/-2.6 cm and point Bp was 1.9+/-2.9 cm (P<.001). CONCLUSION: When the POP-Q examination is performed with simulated apical support, the critical role of level I vaginal support on the position of the anterior and posterior vagina, particularly the anterior vagina, becomes apparent. LEVEL OF EVIDENCE: II.