The impact of COVID-19 pandemic control on vaccine-preventable invasive bacterial diseases in Piedmont (Italy).

PURPOSE: The impact of SARS-CoV-2 pandemic on other pathogens is largely unknown. We aimed to compare the prevalence of vaccine-preventable invasive bacterial infections before and during the pandemic in Piedmont (Italy). METHODS: We defined the monthly incidence of S. pneumoniae, H. influenzae and N. meningitides-invasive diseases from January 2010 to June 2021. Then, we compared the mean monthly cases during the previous 5 years (2015-2019) and the monthly cases in 2020 or 2021. RESULTS: We found significant reductions for invasive pneumococcal diseases (IPDs) in adults and H. influenzae-invasive diseases in 2020 and 2021 in comparison to the previous years, but not for invasive meningococcal diseases and IPDs in children. CONCLUSIONS: Further data are needed to confirm these findings and define possible post-pandemic evolutions in the epidemiology of vaccine-preventable invasive bacterial diseases.

Integrating rapid diagnostics in Gram-negative bloodstream infections of patients colonized by carbapenemase-producing Enterobacterales.

We implemented a fast-track diagnostic approach for Gram-negative bloodstram infections (BSIs) among carbapenemase-producing Enterobacterales (CPE) carriers. Within a large cohort of patients with CPE rectal carriage, 18.1% developed Gram-negative BSIs, of which 69.5% were caused by CPE. Direct matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis provided reliable identification in 97% and 53.8% of monomicrobical blood cultures positive to Enterobacterales and non-fermenting Gram-negative species, respectively. Overall, sensitivity and specificity of NG-Test Carba 5 compared with the composite reference method after discrepant analysis were 100%, in polimicrobial blood cultures too. The combined use of direct MALDI-TOF MS and NG-Test Carba 5 assay might be a reliable and cost-effective tool for accelerating the laboratory diagnosis of CPE BSI in cohorts of high-risk patients such as CPE carriers.

Advanced microscopy analysis of the micro-nanoscale architecture of human menisci.

The complex inhomogeneous architecture of the human meniscal tissue at the micro and nano scale in the absence of artefacts introduced by sample treatments has not yet been fully revealed. The knowledge of the internal structure organization is essential to understand the mechanical functionality of the meniscus and its relationship with the tissue's complex structure. In this work, we investigated human meniscal tissue structure using up-to-date non-invasive imaging techniques, based on multiphoton fluorescence and quantitative second harmonic generation microscopy complemented with Environmental Scanning Electron Microscopy measurements. Observations on 50 meniscal samples extracted from 6 human menisci (3 lateral and 3 medial) revealed fundamental features of structural morphology and allowed us to quantitatively describe the 3D organisation of elastin and collagen fibres bundles. 3D regular waves of collagen bundles are arranged in "honeycomb-like" cells that are comprised of pores surrounded by the collagen and elastin network at the micro-scale. This type of arrangement propagates from macro to the nanoscale.

Does the type of graft affect the outcome of revision anterior cruciate ligament reconstruction? a meta-analysis of 32 studies.

AIMS: Our aim was to perform a meta-analysis of the outcomes of revision anterior cruciate ligament (ACL) reconstruction, comparing the use of different types of graft. MATERIALS AND METHODS: A search was performed of Medline and Pubmed using the terms "Anterior Cruciate Ligament" and "ACL" combined with "revision", "re-operation" and "failure". Only studies that reported the outcome at a minimum follow-up of two years were included. Two authors reviewed the papers, and outcomes were subdivided into autograft and allograft. Autograft was subdivided into hamstring (HS) and bone-patellar tendon-bone (BPTB). Subjective and objective outcome measures were analysed and odds ratios with confidence intervals were calculated. RESULTS: A total of 32 studies met the inclusion criteria. Five studies used HS autografts, eight reported using BPTB autografts, two used quadriceps tendon autografts and eight used various types. Seven studies reported using allografts, while the two remaining used both BPTB autografts and allografts. Overall, 1192 patients with a mean age of 28.7 years (22.5 to 39) and a mean follow-up of 5.4 years (2.0 to 9.6) were treated with autografts, while 269 patients with a mean age of 28.4 years (25 to 34.6) and a mean follow-up of 4.0 years (2.3 to 6.0) were treated with allografts. Regarding allografts, irradiation with 2.5 mrad was used in two studies while the graft was not irradiated in the seven remaining studies. Reconstructions following the use of autografts had better outcomes than those using allograft with respect to laxity, measured by KT-1000/2000 (MEDmetric Corporation) and the rates of complications and re-operations. Those following the use of allografts had better mean Lysholm and Tegner activity scores compared with autografts. If irradiated allografts were excluded from the analysis, outcomes no longer differed between the use of autografts and allografts. Comparing the types of autograft, all outcomes were similar except for HS grafts which had better International Knee Documentation Committee scores compared with BPTB grafts. CONCLUSION: Autografts had better outcomes than allografts in revision ACL reconstruction, with lower post-operative laxity and rates of complications and re-operations. However, after excluding irradiated allografts, outcomes were similar between autografts and allografts. Overall, the choice of graft at revision ACL reconstruction should be on an individual basis considering, for instance, the preferred technique of the surgeon, whether a combined reconstruction is required, the type of graft that was previously used, whether the tunnels are enlarged and the availability of allograft. Cite this article: Bone Joint J 2017;99-B:714-23.

Is there a role for femoral offset restoration during total hip arthroplasty? A systematic review.

Benefits of femoral offset restoration during total hip arthroplasty should be the reduction of bearing surfaces wear, implant loosening and dislocation rates. Modular neck stems ensure offset customization but fretting corrosion and catastrophic failures are well-documented complications. Since clinical evidences are needed to substantiate the effectiveness of femoral offset restoration and promote modular neck choice, we systematically reviewed the literature to ascertain whether femoral offset itself has a proven clinical influence: (1) on bearing surfaces wear, (2) implant loosening, (3) and dislocation rates. A systematic literature screening was conducted to find papers dealing with the influence of femoral offset on wear, dislocation and loosening, including articles with conventional radiographic femoral offset assessment and with comparative design. Observational studies, case reports, instructional course lectures, cadaveric and animal studies as well as biomechanical studies, letters to the editor, surgical techniques or technical notes were all excluded. No limits about publication date were supplied but only papers in English were taken into account. Data were extracted into an anonymous spreadsheet. Offset values, dislocation rates, wear rates, follow-up and surgical approaches were all detailed. Ten manuscripts were finally selected. A statistically significant correlation between femoral offset restoration and the reduction of conventional ultrahigh-molecular-weight polyethylene wear was found in two out of three papers investigating this issue, but no correlations were found between femoral offset and dislocation rates or implant loosening. Femoral offset modification influences ultrahigh-molecular-weight polyethylene liners wear, but no correlation was found with dislocation rates or implant loosening. Advantages on wear can be counterbalanced by the use of hard bearing surfaces or highly cross-linked polyethylene liners, besides the availability of larger femoral heads improving implant stability further reduces the importance of femoral offset restoration by means of modularity. We believe that efforts in restoring femoral offset during total hip arthroplasty do not translate into tangible clinical profits and consequently, we do not advise the routinely usage of modular neck stems in total hip arthroplasty. LEVEL OF EVIDENCE: level III, systematic review of case-control studies.

The diagnostic value of cytohistological urine analysis and cytokeratin 20 in malignant and atypical urothelial cells.

INTRODUCTION: To determine the ability of cytohistology and cytokeratin 20 (CK 20) expression in malignant and atypical cells (AUC) from urine to serve as a diagnostic tool for assessing urothelial carcinoma (UC). METHODS: Diagnoses from 55 urine cytological samples from 55 patients were analyzed and correlated with subsequent biopsy findings. A total of 50 archived urine slides from patients that received a cytological diagnosis and histological follow-up were selected for immunostaining with monoclonal CK 20 antibodies and elaborated by Z-test for proportions. RESULTS: The majority of all positive or atypical smears (24; 89%) were confirmed through histological analysis. The majority of urinary cytological diagnoses reported as negative (15; 54%) were also confirmed through biopsies. The overall sensitivity, specificity, PPV, and NPV were 65%, 83%, 89%, and 54%, respectively. All 13 smears cytologically determined to contain malignant cells, with subsequent biopsies confirming UC, exhibited strong positive staining with the CK 20 antibody. All cases evaluated as benign both cytologically and histologically had negative CK 20 staining. Of the 15 AUC cases with lesions confirmed through biopsies, 11 (73%) had atypical cells that stained positive for CK 20. DISCUSSION: Our results demonstrate the diagnostic value of urinary cytology and confirm CK 20 as an adjunct marker for the diagnosis of UC and for the triage of AUC.

Possible role of tocopherols in the modulation of host microRNA with potential antiviral activity in patients with hepatitis B virus-related persistent infection: a systematic review.

Hepatitis B virus (HBV) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis, hepatocellular carcinoma and liver failure. Recently, the study of the role of microRNA (miRNA) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved. A few studies have investigated the antiviral activity of vitamin E (VE) in chronic HBV carriers. Herein, we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity. A systematic research of the scientific literature was performed by searching the MEDLINE, Cochrane Library and EMBASE databases. The keywords used were 'HBV therapy', 'HBV treatment', 'VE antiviral effects', 'tocopherol antiviral activity', 'miRNA antiviral activity' and 'VE microRNA'. Reports describing the role of miRNA in the regulation of HBV life cycle, in vitro and in vivo available studies reporting the effects of VE on miRNA expression profiles and epigenetic networks, and clinical trials reporting the use of VE in patients with HBV-related chronic hepatitis were identified and examined. Based on the clinical results obtained in VE-treated chronic HBV carriers, we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity. This approach may contribute to the improvement of our understanding of pathogenetic mechanisms involved in HBV infection and increase the possibility of its management and treatment.

Probiotics in the gastrointestinal diseases of the elderly.

Changes of the gut microflora in elderly appear to involve a reduction in numbers of healthy bacteria (lactobacilli and bifidobacteria) and an increase in numbers of potentially pathogenic species. These changes are generally described as gastrointestinal disorders and infections. This review analyses benefits of probiotics in old people, with particular interesting for the latest researches relevant to elderly people, e.g. trials examining enteric infections, antibiotic-associated diarrhea and Clostridium difficile associated diarrhea, functional bowel problems (constipation and irritable bowel syndrome), inflammatory bowel diseases, stimulation of the immune system and prevention of cancer. A growing number of researches indicates that some probiotic strains may help to maintain the health in old people, suggesting both health and cost-saving benefits in offering fermented dairy products. These benefits include: establishment of balanced intestinal microflora; improving colonization resistance and or prevention of diarrhea; reduction of fecal enzymes; reduction of serum cholesterol; reduction of potential mutagenes; reduction of lactose intolerance; synthesis of vitamins; predigestion of proteins.

Immunocytochemistry in Europe: results of the European Federation of Cytology Societies (EFCS) inquiry.

OBJECTIVE: This report describes the results of the first chosen topic of the European Federation of Cytology Societies (EFCS) scientific committee, which concerns the application of immunocytochemistry (ICC) to cytological material. While ICC has become an important ancillary method, not only for diagnosis but also to assess prognostic and predictive factors on cytological material, there are many different methodologies used and the lack of standardization has been criticized. This inquiry aimed first to obtain an overview of the techniques used and second to suggest mechanisms for standardization and quality control. METHODS: We report the results of 28 replies from 13 countries to a web-based inquiry into types of specimens, preparations and technical methods. RESULTS: Conventional smears were the preparations most commonly used, followed by cytospins, cell blocks and liquid-based preparations, in that order. Avidin-biotin complex, labelled streptavidin-biotin or peroxidase anti-peroxidase were used in 61% and enhanced-polymer technology in 39%. Automated staining techniques were used by 64%. More than half used the same antibody dilutions as histopathology although only 20% used cell blocks. CONCLUSION: Reduction of variability by using automation, appropriate controls and customized dilution of antibodies according to different samples could improve the quality of ICC and standardize the techniques, along with quality control and quality assurance measures.

Hemangiopericytoma-solitary fibrous tumour of soft tissue: description of a case showing atypical histological features.

Extrathoracic solitary fibrous tumours have been reported in almost all anatomic sites, but reports of tumours in the extremities or in intramuscular locations, as well as of tumours with atypical histological features and malignant behaviour, are rare. Herein the authors describe a case of hemangiopericytoma-solitary fibrous tumour that arose in the gluteal region of a 47-year-old woman. The tumour showed atypical histological features, such as high cellularity, increased mitotic activity and focal expression of cytokeratins.

[HPV infection: comparison between morphological studies and molecular biology]. / L'infezione da HPV: confronto diagnostico tra indagini morfologiche e biologia molecolare.

Human Papilloma Virus plays an essential role in the development of cervical cancer. We investigated the global prevalence of Human Papilloma Virus infection in a population of 699 women recruited at the Ospedali Riuniti in Foggia for gynaecological controls from September 2005 to March 2007, and compared with a group of 90 women, selected on clinical aspects for Human Papilloma Virus features. The observed prevalence was 27.4%, which is higher that that reported in the literature. In the study group, the most frequent viral type was 16, while type 18 was considerably less frequent compared with other emergent viral types (39, 52, 56, 58, 59). The high prevalence of Human Papilloma Virus-DNA in women with negative cytology or inflammatory changes raises doubts about the utility of the Human Papilloma Virus-DNA method as a primary screening test because of the low cost/benefit ratio. The absence of uniform and standardised reports does not allow objective comparison between different methods of analysis (cytology, colposcopy and molecular biology), pointing out the need for a unique centre for collection and data analysis.

Epithelioid angiomyolipoma of the kidney: case report.

Renal angiomyolipoma is a benign tumour histologically characterized by a mixture of adipose tissue, smooth muscle cells and thick walled blood vessels. Long-believed to be a benign hamartoma, angiomyolipoma is now considered to arise from perivascular epithelioid cells. Epithelioid angiomyolipoma is a rare type of angiomyolipoma, composed partially or completely of epithelioid cells, with a potentially aggressive behaviour. Histologically it can mimic renal cell carcinoma. Positivity for HMB45, Melan A, CD68 and CD117 are useful for diagnosis. Herein, we report the clinicopathologic and immunohistochemical features of a renal tumour composed of large epithelioid mononucleated or multinucleated cells with abundant acidophilic cytoplasm and prominent nucleoli. Despite the morphologic resemblance of this tumour to renal cell carcinoma, its phenotype (HMB45, Melan A and CD68 positivity and keratin negativity) parallels the phenotypic profile of angiomyolipoma. Therefore, immunohistochemistry should be considered when diagnosing this variant of angiomyolipoma.

Interlaboratory reproducibility of liquid-based equivocal cervical cytology within a randomized controlled trial framework.

Within a multicentre controlled trial framework, an external quality control (EQC) was scheduled to evaluate the interlaboratory reproducibility of liquid-based cytology. In particular, this EQC intended to evaluate the reproducibility of the ASCUS diagnosis.A selected set of 30 slides (4 within normal limit cases, 16 atypical squamous cells of undetermined significance; 4 low-grade squamous intraepithelial lesions and 6 high-grade squamous intraepithelial lesions) circulated among the 13 laboratories involved in the trial.Kappa values were obtained from the comparison between individual laboratory diagnoses and majority diagnoses with target diagnoses. Specific kappa values resulted moderate to high for HSIL and low to moderate for LSIL and WNL. Meanwhile, the specific kappa for ASCUS was below 0.4 in 12 of 13 participating laboratories. The lack of reproducibility for ASCUS was not a result of the introduction of this new technology but rather to the low reproducibility of the ASCUS category itself stemming from intrinsic uncertainties in the reporting criteria.

Technical evaluation of the new thin layer device CellSlide (Menarini Diagnostics).

The CellSlide Processor (Menarini Diagnostics) is an automatic computer-controlled instrument, designed to prepare standardized, thin-layer cytological preparations using a filtration process. In this report, this new processor has been tested in a multicentric investigation, designed to evaluate cell recovery, cellular morphology and possible time saved in reading the slide. The results of this study show that the CellSlide processing system is suitable for use in the preparation of liquid-based gynaecology samples. Furthermore, the high-quality smear produced by the CellSlide decreases the reading time by approximately 20-25%.

Differential location and structural specificities of sialic acid-beta-D-Gal sequences belonging to sialoderivatives of rabbit oviduct under hormonal treatment.

Sialoderivatives expressed in the rabbit oviduct under hormonal treatment have been investigated in situ by lectin histochemistry with a view to specifying further regional and temporal specializations which enable ampulla and isthmus to play distinct roles in the reproductive events. Application of MAL II and SNA lectins allowed sialoglycoconjugates containing Sia(alpha2,3)Gal and Sia(alpha2,6)Gal groups to be discriminated. Sialic acid residues linked to Gal(beta1,3)-D-GalNAc sequences were identified using PNA combined with sialidase digestion. Information on structural features of sialic acids were acquired by deacetylation and differential oxidation pretreatments. In both oviductal portions, Sia(alpha2,6) groups were restricted to the luminal surface of the lining epithelium while Sia(alpha2,3) groups were specifically located in the secretory, non-ciliated cells. In the ampullary epithelium, non-acetylated sialic acids alpha2,3-linked to Gal(beta1,3)-D-GalNAc sequences were largely present. Only at ovulation time were sialic acid residues containing acetyl substituents on C4 also found. A great variety of sialic acids were found in the isthmic epithelium which showed the highest expression of acetylated forms at the first hours after the hormonal treatment. The heterogeneity of sialoderivatives differently expressed in the ampulla and isthmus as well as their distinct cycle-dependent modulation suggest that sialylated components may contribute to the molecular and functional specificities within the oviductal epithelium.

Integrating self-referral for mammography into organised screening: results from an Italian experience.

OBJECTIVE: To compare self-referred screenees with respondents to invitation for main performance indicators of mammography screening. SETTING: First round of an organised, population-based screening programme in six districts of northern Italy. METHODS: The screening test was a two-view mammography. Eligible women aged 50-69 years were invited. Self-referred attendees were accepted if they were eligible for screening and had not yet been invited or had been invited >6 months before presentation. Age-specific performance indicators were compared with the calculation of their ratio and 95% confidence intervals (CIs). Total ratios were age standardised. In situ carcinomas were excluded. RESULTS: The eligible population was 183 542 women. There were 112 188 respondents to invitation and 20 280 self-referred attendees. Self-referral rate was inversely related to age. Performance indicators were as follows: recall rate, 5.6% for self-referred attendees vs 5.5% for respondents (ratio 1.02, 95% CI 0.96 to 1.08); total aspiration cytology rate, 37.3% vs 28.3% (1.37, 1.24 to 1.51); biopsy rate, 17.0 vs 12.6 x 1000 (1.51, 1.35 to 1.67); total detection rate, 10.7 vs 7.5 x 1000 (1.70, 1.48 to 1.94); detection rate of pT1 carcinoma, 7.0 vs 6.1 x 1000 (1.35, 1.14 to 1.59); detection rate of pT2-4 carcinoma, 3.5 vs 1.2 x 1000 (3.51, 2.75 to 4.43); false-positive rate, 4.5% vs 4.7% (0.93, 0.87 to 0.99); positive predictive value (PPV) of mammography, 19.1% vs 13.5% (1.59, 1.39 to 1.82); PPV of biopsy, 63.7% vs 60.6% (1.13, 0.98 to 1.29); detected:expected ratio, 5.02 vs 3.37 (1.49, 1.28 to 1.74). All differences were more pronounced among or restricted to women aged 50-54 years. CONCLUSIONS: Self-referred screenees were similar to respondents to invitation in main indicators of screening feasibility such as recall rate and PPV of biopsy, while showing important increases in detection rates and detected:expected ratios, especially among women aged 50-54 years.

Performance indicators of organized cervical screening in Romagna (Italy).

The availability of published data from organized cervical screening programmes in southern Europe is scant. In the Italian area of Romagna, a first round of organized screening (based on a 3-yearly Pap smear for women aged 25-64 years) was initiated between December 1995 and January 1997 and was completed in an average of 42 months (range 36-48 months). The target population included 305 478 women. Of these, 253 949 were eligible and received a personal letter of invitation. Age-specific screening performance indicators were calculated according to standard methods. The response rate within 6 months of invitation was 49.1% (n=124 621). The total participation rate including women who presented later was 61.7% (n=156 735). The recall rate was 35.2 per 1000 of participants (n=5514). Positive cytology results were distributed as follows: atypical squamous cells of un-determined significance/atypical glandular cells of undetermined significance (ASCUS/AGUS) 40.1%, low-grade squamous intraepithelial neoplasia (LGSIL) 48.6%, high-grade squamous intraepithelial neoplasia (HGSIL) 10.7% and carcinoma 0.7%. Compliance to colposcopy follow-up was 93.4% (n=5149). The biopsy rate was 52.4% (n=2696) of patients undergoing colposcopy. The detection rate was 4.5 per 1000 of participants (n=707) for CIN2-3 and 0.5 (n=75) for invasive carcinoma. The proportion of microinvasive carcinomas was 36.0% (n=27). The positive predictive value for CIN2-3/carcinoma was 5.8% for the cytology reports of ASCUS/AGUS, 7.6% for those of LGSIL, 76.5% for those of HGSIL, and 100.0% for those of carcinoma (80.4% for combined HGSIL/carcinoma). The ratio of observed to expected (or prevalent to incident) cases of invasive carcinoma was 2.35 (95% confidence interval (CI) 1.85-2.95). In conclusion, most early results of the programme were compatible with an acceptable performance.