Klippel-Feil syndrome. When using fiberoptic bronchoscopy guide, a case report

Klippel-Feil syndrome is a rare disease with congenital musculoskeletal condition characterized by faulty segmentation of cervical vertebrae and consists of cervical vertebra fusions with limitation of head movements, short neck and low posterior hairline. In several cases the syndrome is associated with cardiovascular malformations. Patients affected by Klippel-Feil syndrome could be an anesthetic challenge, not only during cardiac surgery. We are presenting a case of Klippel-Feil Syndrome in an adult patient, who was operated on for a pulmonary valve insufficiency in a previously corrected Tetralogy of Fallot Syndrome. We are going to discuss the features of this rare syndrome

Neoadjuvant treatment in pancreatic cance. Evidence-based medicine? A systematic review and meta-analysis

Neoadjuvant treatment in non-metastatic pancreatic cancer (PaC) has the theoretical advantages of downstaging the tumor, sterilizing any present systemic undetectable disease, selecting patients for surgery and administering therapy to each patient. The aim of this systematic review is to analyze the state of the art on neoadjuvant protocols for non-metastatic PaC. A literature search over the last 10 years was conducted, and papers had to be focused on resectable, borderline resectable (BLR) or locally advanced (LA) histo- or cytologically proven PaC; to be prospective studies or prospectively collected databases; to report percentage of protocol achievement and survival data at least in an intention-to-treat (ITT) analysis. Twelve studies were eligible for systematic review. Studies included a total of 624 patients: 248 resectable, 268 BLR, 71 LA and 37 non-specified. All studies were included for meta-analysis. ITT overall survival (OS) was 16.7 months (95% CI 15.16-18.26 months); for resected patients OS was 22.78 months (95% CI 20.42-25.16), and for eventually non-resected patients it was 9.89 months (95% CI 8.84-10.96). Neoadjuvant approaches for resectable, BLR and LA PaC are spreading. Outcomes tend to be better outside an RCT context, but strong evidences are lacking. Actually such treatments should be performed only in a randomized clinical trial setting

Impact of sarcopenia on outcomes after pancreatectomy for malignancy

Background: Sarcopenia, which is a subclinical loss of skeletal muscle mass as measured by cross-sectional imaging, is commonly observed in patients with malignancy. Few studies have examined the association between the presence of sarcopenia and outcome following surgery. The aim of this study is to evaluate the prevalence of sarcopenia and to investigate its impact on short- and long-term outcomes in patients who underwent pancreatectomy for malignancy. Materials and Methods: A retrospective review of a pancreatectomy database was performed. Skeletal muscle index (SMI) was measured on preoperative cross-sectional imaging in 144 patients undergoing pancreatectomy for cancer between 2007 and 2014. Sarcopenia was defined, according to the international consensus, as an SMI <52.4 cm2 /m2 and <38.9 cm2 /m2 for men and women respectively. The prevalence and impact of sarcopenia on morbidity, mortality, disease-free and overall survivals was assessed relative to other clinicopathological factors. Results: Mean age was 67.15 years and 51% was female. Pancreatic adenocarcinoma represents 66.7% of all cases. Pancreaticoduodenectomy was performed in 114 cases (79.2%). Margin status was R0 in 76.9%. Mean BMI was 24.85 Kg/m2 and mean SMI was 35,43 cm2 /m2 . One hundred and eight (74.5%) were sarcopenic, 37 (43.5%) were overweight/ obese and 43 (29.7%) were both (p = 0.041). Sarcopenia was significantly related to histology, sex, BMI and albumin. Overall morbidity and 90-days mortality were 50.7% and 9.1% respectively. The median follow up was 21 months. Overall and disease-free survival rate were 25,44 months and 11,84 months respectively. Sarcopenia was associated to a not statistically significant increased risk of overall morbidity, mortality and shorter disease- free and overall survivals after pancreatic surgery for cancer. Conclusions: Sarcopenia was found in 74.5% of cancer patients underwent pancreatectomy. It is an occult condition in overweight/obese patients but can be identified using CT scans. This condition, as defined by international consensus, is not associated with worse short-term and long-term outcomes after surgery

Impaired Ca2+ sensitivity of a novel GCAP1 variant causes cone dystrophy and leads to abnormal synaptic transmission between photoreceptors and bipolar cells

Guanylate cyclase-activating protein 1 (GCAP1) is involved in the shutdown of the phototransduction cascade by regulating the enzymatic activity of retinal guanylate cyclase via a Ca2+/cGMP negative feedback. While the phototransduction-associated role of GCAP1 in the photoreceptor outer segment is widely established, its implication in synaptic transmission to downstream neurons remains to be clarified. Here, we present clinical and biochemical data on a novel isolate GCAP1 variant leading to a double amino acid substitution (p.N104K and p.G105R) and associated with cone dystrophy (COD) with an unusual phenotype. Severe alterations of the electroretinogram were observed under both scotopic and photopic conditions, with a negative pattern and abnormally attenuated b-wave component. The biochemical and biophysical analysis of the heterologously expressed N104K-G105R variant corroborated by molecular dynamics simulations highlighted a severely compromised Ca2+-sensitivity, accompanied by minor structural and stability alterations. Such differences reflected on the dysregulation of both guanylate cyclase isoforms (RetGC1 and RetGC2), resulting in the constitutive activation of both enzymes at physiological levels of Ca2+. As observed with other GCAP1-associated COD, perturbation of the homeostasis of Ca2+ and cGMP may lead to the toxic accumulation of second messengers, ultimately triggering cell death. However, the abnormal electroretinogram recorded in this patient also suggested that the dysregulation of the GCAP1-cyclase complex further propagates to the synaptic terminal, thereby altering the ON-pathway related to the b-wave generation. In conclusion, the pathological phenotype may rise from a combination of second messengers' accumulation and dysfunctional synaptic communication with bipolar cells, whose molecular mechanisms remain to be clarified

Prevalence of Asymptomatic SARS-CoV-2 Infection in the General Population of the Veneto Region: Results of a Screening Campaign with Third-Generation Rapid Antigen Tests in the Pre-Vaccine Era

The aim of our study was to ascertain the prevalence of SARS-CoV-2 infection in the general population during a period of moderate risk, just before Italy started to implement its vaccination campaign. A third-generation antigenic nasal swab sample was collected by a healthcare provider, and all individuals testing positive subsequently had a nasopharyngeal swab for molecular testing; the result was used to calculate the positive predictive value. The population consisted of 4467 asymptomatic adults with a mean age of 46.8 +/- 16.00 years. The 62.2% tested for the first time, while 37.8% had previously undergone a mean 2.2 tests for SARS-CoV-2. With 77 of our overall sample reporting they had previously tested positive for COVID-19 and 14 found positive on our screening test, the overall estimated prevalence of the infection was 0.31%. Nine of the 14 cases were confirmed on molecular testing with a PPV of 64.3%. The mean age of the individuals testing positive was 38.1 +/- 17.4. Based on the timing of symptom onset, six of the above cases were classified as false negatives, and the adjusted estimated prevalence was 0.34%. Describing levels of infection in a general population seems to be very difficult to achieve, and the universal screening proved hugely expensive particularly in a low-prevalence situation. Anyway, it is only thanks to mass screening efforts that epidemiological data have been collected. This would support the idea that routine screening may have an impact on mitigating the spread of the virus in higher-risk environments, where people come into contact more frequently, as in the workplace

Attitudes of university students towards mandatory COVID-19 vaccination policies. A cross-sectional survey in Rome, Italy

Mandatory vaccination (MV) against COVID-19 is a contentious topic. In this study, we used logistic regression models to identify attitudes among Sapienza University students towards MV for COVID-19. We considered three different scenarios: mandatory COVID-19 vaccination (MCV) for healthcare workers (HCWs) (Model 1), for all people aged ≥ 12 years (Model 2), and for admission to schools and universities (Model 3). We collected 5287 questionnaires over a six-month period and divided these into three groups (September-October 2021, November-December 2021, and January-February 2022). MCV for HCWs was the most strongly supported policy (69.8% in favour), followed by MCV for admission to schools and universities (58.3%), and MCV for the general population (54.6%). In a multivariable analysis, the models showed both similarities and differences. There was no association of socio-demographic characteristics with the outcomes, apart from being enrolled in non-healthcare courses, which negatively affected Models 2 and 3. A greater COVID-19 risk perception was generally associated with a more positive attitude towards MCV, although heterogeneously across models. Vaccination status was a predictor of being in favour of MCV for HCWs, whereas being surveyed in November-February 2022 favoured MCV for admission to schools and universities. Attitudes towards MCV were variable across policies; thus, to avoid unintended consequences, these aspects should be carefully considered by policymakers

A Perfusion Bioreactor for Longitudinal Monitoring of Bioengineered Liver Constructs

In the field of in vitro liver disease models, decellularised organ scaffolds maintain the original biomechanical and biological properties of the extracellular matrix and are established supports for in vitro cell culture. However, tissue engineering approaches based on whole organ decellularized scaffolds are hampered by the scarcity of appropriate bioreactors that provide controlled 3D culture conditions. Novel specific bioreactors are needed to support long-term culture of bioengineered constructs allowing non-invasive longitudinal monitoring. Here, we designed and validated a specific bioreactor for long-term 3D culture of whole liver constructs. Whole liver scaffolds were generated by perfusion decellularisation of rat livers. Scaffolds were seeded with Luc(+)HepG2 and primary human hepatocytes and cultured in static or dynamic conditions using the custom-made bioreactor. The bioreactor included a syringe pump, for continuous unidirectional flow, and a circuit built to allow non-invasive monitoring of culture parameters and media sampling. The bioreactor allowed non-invasive analysis of cell viability, distribution, and function of Luc(+)HepG2-bioengineered livers cultured for up to 11 days. Constructs cultured in dynamic conditions in the bioreactor showed significantly higher cell viability, measured with bioluminescence, distribution, and functionality (determined by albumin production and expression of CYP enzymes) in comparison to static culture conditions. Finally, our bioreactor supports primary human hepatocyte viability and function for up to 30 days, when seeded in the whole liver scaffolds. Overall, our novel bioreactor is capable of supporting cell survival and metabolism and is suitable for liver tissue engineering for the development of 3D liver disease models

Prevalence of SARS-CoV-2 infection and associated risk factors. A testing program and nested case-control study conducted at Sapienza University of Rome between March and June 2021

Background: To safely resume in-person activities during the COVID-19 pandemic, Sapienza University of Rome implemented rigorous infection prevention and control measures, a successful communication campaign and a free SARS-CoV-2 testing program. In this study, we describe the University's experience in carrying out such a program in the context of the COVID-19 response and identify risk factors for infection. Methods: Having identified resources, space, supplies and staff, from March to June 2021 Sapienza offered to all its enrollees a molecular test service (8.30 AM to 4 PM, Monday to Thursday). A test-negative case-control study was conducted within the program. Participants underwent structured interviews that investigated activity-related exposures in the 2 weeks before testing. Multivariable conditional logistic regression analyses were performed. Adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) were calculated. Results: A total of 8,959 tests were administered, of which 56 were positive. The detection trend followed regional tendencies. Among 40 cases and 80 controls, multivariable analysis showed that a known exposure to a COVID-19 case increased the likelihood of infection (aOR: 8.39, 95% CI: 2.38–29.54), while having a job decreased it (aOR: 0.23, 95% CI: 0.06–0.88). Of factors that almost reached statistical significance, participation in activities in the university tended to reduce the risk (aOR: 0.32, 95% CI: 0.09–1.06), while attendance at private gatherings showed an increasing risk trend (aOR: 3.48, 95% CI: 0.95–12.79). Age, gender, activities in the community, visiting bars or restaurants, and use of public transportation were not relevant risk factors. When those students regularly attending the university campus were excluded from the analysis, the results were comparable, except that attending activities in the community came close to having a statistically significant effect (aOR: 8.13, 95% CI: 0.91–72.84). Conclusions: The testing program helped create a safe university environment. Furthermore, promoting preventive behavior and implementing rigorous measures in public places, as was the case in the university setting, contributed to limit the virus transmission