Clinical Features and Complications of the HLA-B27-associated Acute Anterior Uveitis: A Metanalysis

In this article, we report a literature-based metanalysis we have conducted to outline the clinical features of the HLA-B27 Acute Anterior Uveitis (AAU). The examined material was based on observational studies in which participants were affected by Acute Anterior Uveitis and divided into HLA B27+ and HLA B27–. We performed a search on articles with the words “HLA B27 uveitis” dated before May 2014. Among these, 29 articles were selected for a second review. After a further evaluation, 22 articles were analyzed. The clinical characteristics studied in the metanalysis were: (1) systemic disease; (2) sex distribution; (3) laterality; (4) visual acuity; (5) hypopion; (6) anterior chamber’s fibrin; (7) elevated intraocular pressure (IOP) during inflammation; (8) glaucoma; (9) posterior synechiae; (10) cataract; (11) cystoid macular edema; (12) papillitis. We have calculated a relative risk (RR) for each outcome measured. The results obtained remark some of the peculiar features linked to the HLA B27 Acute Anterior Uveitis, such as strong association with ankylosing spondylitis (RR = 6.80) and systemic diseases (RR = 9.9), male prevalence (RR = 1.2), unilateral (RR = 1.1) or alternating bilateral (RR = 2.2) involvement, hypopion (RR = 5.5), fibrinous reaction and even papillitis (R = 7.7). Simultaneous bilateral (RR = 0.3) AAU is more frequent in HLA-B27 negative form. We report higher risk of elevated IOP and glaucoma (RR = 0.6) in B27– Acute Anterior Uveitis. No significant difference between HLA B 27 positive and negative AAU was observed according to final visual acuity and complications such as posterior synechiae, cataract, and maculare edema. We trust that this will inform on the clinical evaluation and therapeutic decision in addressing a still ill-defined ophthalmologic condition.     

Total and not bevacizumab-bound vascular endothelial growth factor as potential predictive factors to bevacizumab-based chemotherapy in colorectal cancer

AIM: To identify suitable biomarkers of response to bevacizumab(BV)- it remains an open question. The measurement of serum vascular endothelial growth factor(VEGF) has been proposed as a predictive factor for this drug, even if literature data are contradictory. METHODS: We prospectively evaluated the role of BV, total and not BV-bound VEGF and angiopoietin-2(Ang-2) serum levels as potential predictive factors of response for BV in combination with an oxaliplatinbased chemotherapy. BV, Ang-2, total and not BVbound VEGF levels were measured at baseline, before 2~(nd) and 5~(th) cycle of oxaliplatin-based chemotherapy in 20 consecutive metastatic colorectal cancer patients. RESULTS: Results were correlated to response to treatment. Variability in BV levels have been found, with decreased level in less responding patients. In particular, the concentration of BV increased of 3.96 ± 0.69 folds in serum of responsive patients after 3 more cycles of therapy compared to those with stable or progressive disease with a 0.72 ± 0.25 and 2.10 ± 0.13 fold increase, respectively. The determination of free and total VEGF demonstrated that the ratio between the two values, evaluated immediately before the 2~(nd) and the 5~(th) cycle of therapy, decreased from 26.65% ± 1.33% to 15.50% ± 3.47% in responsive patients and from 53.41% ± 4.75 to 34.95% ± 2.88% in those with stable disease. Conversely, in those with progression of disease, the ratio showed the opposite behavior coming up from 25.99% ± 5.23% to 51.71% ± 5.28%. The Ang-2 levels did not show any relationship. CONCLUSION: Our data show that the ratio of not BV-bound VEGF to total VEGF serum and BV plasma concentrations for predicting the response to BV plus oxaliplatin-based chemotherapy could be a promising biomarker of response to BV.     

phosphatase and tensin homolog is a differential diagnostic marker between nonalcoholic and alcoholic fatty liver disease

AIM: To investigate the protein expression of phosphatase and tensin homolog(PTEN) in human liver biopsies of patients with alcoholic and non-alcoholic liver disease.METHODS: PTEN protein expression was assessed by immunohistochemistry in formalin-fixed, paraffinembedded liver sections of patients with non-alcoholic fatty liver disease(NAFLD)(n = 44) or alcoholic liver disease(ALD)(n = 25). Liver resections obtained from 3 healthy subjects candidate for partial liver donation served as controls. Histological evaluations were performed by two experienced pathologists, and diagnoses established based on international criteria. The intensity of the PTEN staining in nuclei was compared between steatotic and non-steatotic areas of each liver fragment analyzed. For each liver specimen, the antibody-stained sections were examined and scored blindly by three independent observers, who were unaware of the patients' clinical history.RESULTS: In healthy individuals, PTEN immunostaining was intense in both the cytoplasm and nuclei of all hepatocytes. However, PTEN was strongly downregulated in both the nucleus and the cytoplasm of hepatocytes from steatotic areas in patients with NAFLD, independently of the disease stage. In contrast, no changes in PTEN protein expression were observed in patients with ALD, regardless of the presence of steatosis or the stage of the disease. The degree of PTEN downregulation in hepatocytes of patients with NAFLD correlated with the percentage of steatosis(r = 0.3061, P = 0.0459) and the BMI(r = 0.4268, P = 0.0043). Hovewer, in patients with ALD, PTEN expression was not correlated with the percentage of steatosis with or without obesity as a confounding factor(P = 0.5574). Finally, PTEN expression level in steatotic areas of ALD patients was significantly different from that seen in steatotic areas of NAFLD patients(P 0.0001).CONCLUSION: PTEN protein expression is downregulated early in NAFLD, but not in ALD. PTEN immunohistochemical detection could help in the differential diagnosis of NAFLD and ALD.     

Malignancies in bullous pemphigoid: A controversial association

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disorder that has been reported to be associated with malignancies. Some authors described several cases of pemphigoid associated with malignancies (PAM); however, the evidence of this correlation still remains controversial. Several theories have been postulated to explain the relationship between malignant neoplasms and BP; the main theory suggests that antibodies directed against tumor‐specific antigens of malignant cells may cross‐react with antigens (like BP antigens) in the basement membrane zone leading to the formation of blisters. We performed an extensive review of the English published work focusing on the epidemiology, the pathogenetic theories and the clinical and histological aspects of the disease. We identified 40 cases of PAM: of these, seven cases were associated with hematological malignancies and 33 with solid tumors. Physicians should be aware of the existence of PAM and we suggest an oncological screening in early‐onset pemphigoid, in patients with a former oncological history, in those with signs and symptoms that could be related to a neoplasm and in BP refractory to common immunosuppressive therapy.     

Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia

Spastic paraplegia type 4 is caused by mutations in the gene that encodes spastin (SPG4), a member of the AAA protein family. A cohort of 34 unrelated Italian patients with pure spastic paraplegia, of which 18 displayed autosomal dominant inheritance and 16 were apparently sporadic, were screened for mutations in the SPG4 gene by denaturing high performance liquid chromatography. We identified a previously reported mutation in a sporadic patient with pure hereditary spastic paraplegia. We also identified eight unrelated patients with pure autosomal dominant hereditary spastic paraplegia carrying five novel mutations in the SPG4 gene (one missense mutation, c.1304 C>T; one nonsense mutation, c.807C>A; two frameshift mutations, c.1281dupT, c.1514_1515insATA; and one splicing mutation, c.1322-2A>C). The frequency for SPG4 mutations detected in autosomal dominant hereditary spastic paraplegia was 44.4%. This study contributes to expand the spectrum of SPG4 mutations in Italian population.     

Tympanic reperforation in myringoplasty: evaluation of prognostic factors

OBJECTIVES: The most frequent failure in myringoplasty is reperforation. This complication appears at a rate of 7% to 27%. The aim of this study was to evaluate the importance of the principal prognostic factors to the risk of reperforation. METHODS: This is a study of prognosis based on an inception cohort. The prognostic factors considered in the study refer to clinical and surgical aspects; follow-up ranged from 5 to 7 years (mean, 68 months). The study was performed on 212 patients with or without otorrhea who underwent operation for tympanic perforation. All subjects underwent myringoplasty by means of an underlay or overlay technique depending on the size and site of the perforation. RESULTS: Healing of the tympanic perforation was obtained in 182 cases (86%). Age, otorrhea, status of the contralateral ear, and conductive hearing loss did not significantly affect the outcome of surgery. On the other hand, time from surgery, the site of perforation, the type of anesthesia, the approach, the surgical technique, and the type of graft were significantly related to the outcome. CONCLUSIONS: In the analysis of our results, the surgical approach proved to be the principal prognostic factor in the anatomic outcome of myringoplasty. The results obtained suggest that the principal factors influencing the outcome of myringoplasty are technical and not clinical.     

Impact of celecoxib on capecitabine tolerability and activity in pretreated metastatic breast cancer: results of a phase II study with biomarker evaluation

BACKGROUND: Preclinical evidence suggests that the cyclo-oxygenase-2 (COX-2) enzyme plays an important role in breast cancer progression. The aim of the present phase II study was to determine the activity and safety of the combination of the COX-2 inhibitor celecoxib with capecitabine in metastatic breast cancer (MBC) patients pretreated with anthracyclines and/or taxanes. METHODS: Eligible patients received capecitabine 1,000 mg/m(2) twice daily on days 1-14 every 21 days and celecoxib 200 mg twice daily, continuously, until disease progression or unacceptable toxicity. RESULTS: About 42 pretreated MBC patients were enrolled into the study. Median number of previous chemotherapy lines for metastatic disease was 2 (0-3). Seven patients (19%) responded to treatment while disease stabilization occurred in 17 patients (40.5%). Overall, 20 patients (47.5%) achieved clinical benefit [objective responses (CR) plus stable disease (SD) >/=6 months]. Median time to progression (TTP) and median overall survival (OS) were 5.2 and 17.8 months, respectively. Treatment was very well tolerated: grade 3 toxicities were observed in only five patients, respectively, and no grade 4 adverse events were reported. Celecoxib was never discontinued for toxicity. Analysis of COX-2 expression in the 22 patients with available tissue revealed a significantly longer TTP and OS for patients whose tumors over-expressed COX-2. CONCLUSIONS: The combination of capecitabine and celecoxib is active and safe in far advanced MBC patients. Interestingly, this association resulted in a lower-than-expected toxicity, as compared to single-agent capecitabine. The clinical relevance of COX-2 as determinant of sensitivity to treatment with celecoxib should be further evaluated in larger series of patients.     

Impact of COVID-19 prevention measures on risk of health care-associated Clostridium difficile infection

Clostridium difficile is the most common pathogen between health care-associated infections and its incidence has increased during the last years. lack of enough evidence about effective hygiene interventions to prevent this disease. Due to the coronavirus disease 2019 (COVID?19) pandemic, several strategies to reduce microorganism spread were adopted in hospital setting. The objective of this study was to establish whether such strategies can reduce health care associated C difficile infection (HA-CDI) incidence. We found that, during the pandemic (2020) HA-CDI incidence was significantly lower with respect to the previous years. This work demonstrates that maintaining this level of attention regarding control activities related to prevention of microorganism transmission significantly reduce HA-CDI and related expenses in terms of health costs and human lives.