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Background Gestational diabetes mellitus (GDM) incidence is increasing worldwide. It represents a major risk factor for adverse foetal-maternal outcomes. Awareness among women in regard to GDM-related risks (in particular foetus ones) has been proven to have an impact on compliance with recommendations. Therefore we aimed to evaluate the efficacy of our post-diagnosis counselling, that informs affected women of the GDM related risks for complications, in determining an adequate level of understanding. Method This is a cohort study involving 400 women undergoing the 24-28 weeks 75 g oral glucose tolerance test. Two hundred women diagnosed with GDM received the post-diagnosis counselling (treatment group) and two hundred women diagnosed without did not receive any counselling (control group). Both populations were surveyed with a 5 question questionnaire regarding their awareness about GDM foetal-maternal related risks. Their level of education about GDM foetal-maternal related risks, estimated according to the number of correct answers, was scored as: primary (score 0-1), secondary (score 2-3) or tertiary (score 4-5). Results Most of the women in the treatment group after receiving the post-diagnosis counselling have demonstrated a secondary level of education 132/200 (66%). Their mean level of awareness was higher in comparison to the control group 2.6 ± 1.8 (SD) versus 2.14 ± 1.8 (SD) p value = 0.012. In particular, they’ve demonstrated to be more aware of the risks for the foetus to become macrosomic (p = 0.004) or to die in utero (p = 0.0001). A high level of education and to have had previous pregnancies positively affected correct answers. Conclusions Our post-diagnosis counselling has played a role in improving women awareness about GDM foetal-maternal related risks. Future study will explore the impact of women’s level of awareness on glycaemic control.

The efficacy of platelet-rich plasma in the treatment for Achilles tendinopathy is debated. Therefore, it is important to know which factors, related to the subjects and/or the disease, are associated with positive or negative outcomes. Aim of this study was to evaluate in a large cohort of patients with Achilles mid-portion tendinopathy which variables were independently associated with a positive outcome after platelet-rich plasma treatment. Eighty-four subjects with Achilles tendinopathy were evaluated by means of VISA-A score and ultrasound and treated with a single platelet-rich plasma injection once a week for 3 weeks. Afterward, a rehabilitation program, based on eccentric training, was implemented. At 3 and 6 months, the relationship between the mean VISA-A score and the following putative predictors was evaluated: sex, age, physical activity, sport, smoking, metabolic risk factors, BMI, symptoms duration, tendon damage, neovessels, adherence to eccentric training. Finally, the percentage of clinically evident positive outcomes (defined as an increase in VISA-A score ≥ 20 points) related to each variable was computed. At final follow-up, using the General Linear Model for Repeated Measures procedure, male sex (0.02), age ≤ 40 (0.05) and adequate eccentric training (0.02) were found to be independently associated with a significant increase in the mean VISA-A score. Moreover, the clinically evident positive outcomes, as previously defined, were significantly associated with male sex (0.01), age ≤ 40 (0.000), BMI ≤ 25 (0.001), symptoms duration ≤ 12 months (0.02) and good adherence to eccentric training (0.004). Younger age, male sex and good adherence to eccentric training can be considered predictors of better results after platelet-rich plasma therapy in Achilles tendinopathy

Iatrogenic perforations are severe complications of gastrointestinal endoscopy; therefore, their management should be adequately planned. A 77-year-old man with a history of diverticulosis underwent a colonoscopy for anemia. During the procedure, an iatrogenic perforation occurred suddenly in the sigmoid colon, near a severe angle among the numerous diverticula. Through-the-scope clips were immediately applied to treat it and close mucosal edges. Laboratory tests showed increased levels of inflammation and infection, and although there were no complaints of abdominal pain, the patient had an extremely distended abdomen. A multidisciplinary board began management based on a conservative approach. Pneumoperitoneum was treated with computed tomography-assisted drainage. After 72 hours, his intestinal canalization and laboratory tests were normal. Though this adverse event is rare, a multidisciplinary board should be promptly gathered upon occurrence, even if the patient appears clinically stable, to consider a conservative approach and avoid surgical treatment.

Spinal Infection (SI) is an infection of vertebral bodies, intervening disc, and/or adjoining para-spinal tissue. It represents less than 10% of all skeletal infections. There are numerous factors that predispose to developing a SI. Due to the low specificity of signs, delayed diagnosis is common. Hence, SI may be associated with poor outcomes. Diagnosis of SI must be supported by clinicopathological and radiological findings. MRI is a reliable modality of choice. Treatment options vary according to the site of the infection, disease progression, neurology, presence of instability, and general condition of the subject. Conservative treatment (orthosis/ bed-rest + antibiotics) is recommended during the early course with no/ lesser degree of neurological involvement and to medically unfit patients. Nevertheless, when conservative measures alone fail, surgical interventions must be considered. The use of concomitant antimicrobial drugs intravenously during initial duration followed by oral administration is a necessity. Controversies exist regarding the optimal duration of antimicrobial therapy, yet never given less than six weeks. Heterogeneity in clinical picture and associated co-morbidities with a range of treatment modalities are available; however, a common applicable guideline for SI does not exist. Managing SI must be tailored on a case-to-case basis.

Background: Blood culturing remains the mainstream tool to inform an appropriate treatment in hospital-acquired bloodstream infections and to diagnose any bacteremia. Methods: A retrospective investigation on the prevalence of Gram-negative bacteria (GNB) and their resistance in hospitalized patients by age, sex, and units from blood cultures (BCs) was conducted from January 2018 to April 2020 at Sant’Elia hospital, Caltanissetta, southern Italy. We divided the patient age range into four equal intervals. Results: Multivariate demographic and microbiological variables did not show an association between bacteria distributions and gender and age. The distribution by units showed a higher prevalence of Klebsiella pneumoniae and Acinetobacter baumannii in the intensive care unit (ICU) and Escherichia coli in the non-intensive care units (non-ICUs). The analysis of antibiotic resistance showed that E. coli was susceptible to a large class of antibiotics such as carbapenem and trimethoprim-sulfamethoxazole. K. pneumoniae showed a significant susceptibility to colistin, tigecycline, and trimethoprim-sulfamethoxazole. From the survival analysis, patients with E. coli had a higher survival rate. Conclusions: The authors stress the importance of the implementation of large community-level programs to prevent E. coli bacteremia. K. pneumoniae and E. coli susceptibility patterns to antibiotics, including in the prescription patterns of general practitioners, suggest that the local surveillance and implementation of educational programs remain essential measures to slow down the spread of resistance and, consequently, increase the antibiotic lifespan.

Purpose: Cancer-related cognitive impairment (CRCI) has been reported in non-central nervous system neoplasms survivors. The purpose of this study was to evaluate the perception of cognitive decrement in patients undergoing surgical and / or medical therapy for gynecological cancers. Methods: All women diagnosed with primary gynecological cancer and undergoing active medical treatment have been enrolled in a prospective study. Before starting treatment (T1) and 6 months after the end of treatment (T2), patients were interviewed to evaluate the effects of cancer treatment on perceived cognitive function (using FACT-Cog -version 3), on depression (using Beck Depression Inventory-II test) and on quality of life (using EORTC-QLQC-30). Age, education level, marital status, lifestyle, menopausal state at diagnosis, cancer type, cancer FIGO stage, treatment modality was also recorded. The differences between baseline and post-treatment results have been evaluated with Student's t test. The results have been stratified by the menopausal state at diagnosis, type of tumor (endometrial, cervical, ovarian, vulvar) disease stage and type of treatment (chemotherapy or radiotherapy). Results: Seventy-three patients were included. A significant reduction in perceived cognitive impairments was demonstrated at T2 (CogPCI: 61.35 ± 13.83 vs 55.05 ± 16.56; p < 0.05). On the contrary, a significant improvement was shown in depression state (BDII: 21.14 ± 11.23 vs 12.82 ± 12.33, p < 0.005). The menopausal state at surgery, tumor site, stage and treatment modality seem to influence the variables analyzed. Conclusion: CRCI is a true risk also in gynecological cancer survivors. The cognitive impairment does not seem to be dependent on depression state after treatment or to a menopausal condition. Assessing cognitive decline in cancer survivorship is essential for ensuring the optimum quality of life and functioning.

Objective to evaluate the impact of the COVID-19 pandemic on the obstetrics and gynecology residency training program in Italy. Study design This was a cross-sectional survey study aimed to assess the impact of the COVID-19 pandemic on the obstetrics and gynecology residency training program in Italy. An online survey with 45 questions was sent and completed anonymously by residents after accepting an informed consent. The invitation to the online survey was sent to all the Italian residents in obstetrics and gynecology. Those on maternity leave at the time of the study were excluded. Residents were asked about their routinely activity before the COVID-19 pandemic, and to report the reduction in their clinical practice. They were also asked about psychological impact of COVID-19 on their clinical practice. Results 933 Italian residents in obstetrics and gynecology, were invited for this survey study. Four-hundred and seventy-six (51 %) completed the survey and were included in the study. Three-hundred and eighty-seven (81.3 %) were female, and 89 (18.7 %) were male. Residents age ranged from 25 to 42. In 71,8 % (342/476) of the cases residents work in a COVID-19 reference Hospitals. One-hundred and eighty-four out of 76 residents (38.6 %) were tested on RT-PCR assay of nasal and pharyngeal swab specimens, and of them 12/184 (6.5 %) were positive to SARS−COV-2. Regarding the use of personal protective equipment (PPE), 267 (56.1 %) reported to receive adequate device, and 379 (79.6 %) felt to be well informed about prevention and management protocols. Three-hundred and thirty-one residents (69.5 %) reported to have managed COVID-19 positive patients. For 54,7 % of respondent residents, training activity in general decreased significantly during the COVID-19 epidemic. A one-third reduction was reported in 31,4 % of the cases, whereas a total suspension of the training in 9,9 % of the cases. In 89,3 % of cases the reduction was caused by the reorganization of work. Anxiety about the professional future was reported in 84 % of the residents, and 59 % of them had the perception that their training was irreversibly compromised. Conclusions Among Italian residents in obstetrics and gynecology, COVID-19 pandemic was associated with a significant training impairment.

Clubfoot is the most frequent congenital malformation of the foot, affecting more than 1–2 subjects per 1.000 newborns. Without appropriate treatment, a child with congenital clubfoot will never be able to walk physiologically with a dramatic impact on the quality of life. In the last decades, different corrective solutions have been proposed, and there is rising scientific evidence that the Ponseti non-invasive method is safe and effective in the treatment of the clubfoot. So, what should a general paediatrician know about this condition and what should he concretely do in the suspect of a congenital clubfoot?

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy from a first episode psychosis cohort that includes 136 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC-GSH, HP and SFG volumes, and age at onset, could potentially be biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

BACKGROUND Nowadays there is an increasing use of transcranial magnetic stimulation (TMS) both in neurological and psychiatric fields. After Food and Drug Administration approval of TMS for the therapy of treatment-resistant depression, TMS has been widely used in the context of mood disorders (MD). However, growing reports regarding the possibility of developing hypomanic/manic switch (HMS) have generated concern regarding its use in MDs. AIM To investigate the actual risk of developing HMS due to TMS in the treatment of MD. METHODS We led our research on PubMed, Scopus and Web of Science on March 22, 2020, in accordance to the PRISMA guidelines for systematic review. Only double blind/single blind studies, written in English and focused on the TMS treatment of MD, were included. A meta-analysis of repetitive TMS protocol studies including HMS was conducted using RevMan 5.4 software. The assessment of Risk of Bias was done using Cochrane risk of bias tool. This protocol was registered on PROSPERO with the CRD42020175811 code. RESULTS Twenty-five studies were included in our meta-analysis: Twenty-one double blind randomized controlled trials (RCT) and four single blind-RCT (no. of subjects involved in active stimulation = 576; no. of subjects involved in sham protocol = 487). The most frequently treated pathology was major depressive episode/major depressive disorder, followed by resistant depression, bipolar depression and other MD. The majority of the studies used a repetitive TMS protocol, and the left dorsolateral prefrontal cortex was the main target area. Side effects were reported in eight studies and HMS (described as greater energy, insomnia, irritability, anxiety, suicidal attempt) in four studies. When comparing active TMS vs sham treatment, the risk of developing HMS was not significantly different between conditions. CONCLUSION Applying the most usual protocols and the appropriate precautionary measures, TMS seems not to be related to HMS development.

Trigeminal neuralgia (TN) caused by vertebrobasilar artery (VBA) compression is a rare event, reported between 2 and 6% (Linskey et al. J Neurosurg 81:1-9,1992, Vanaclocha et al.World Neurosurg 96:516-529,2016) of the time. Microvascular decompression (MVD) is advised for drug-resistant pain and, although technically challenging, is associated with an excellent outcome in current literature (Apra et al.Neurosurg Rev 40:577-582,2017, Cruccuet al. EurJ Neurol 15:1013-1028,2008, Linskey et al. J Neurosurg 81:1-9,1992). The authors performed a systematic review and meta-analysis of the literature examining the rate of MVD for trigeminal neuralgia caused by VBA compression and the post-operative outcome. The systematic search of three databases was performed for studies published between January 1990 and October 2020. Random-effects meta-analysis was used to pool the analyzed outcomes, and random-effects meta-regression was used to examine the association between the effect size and potential confounders. Funnel plot followed by Egger’s linear regression was used to test publication bias. We included 9 studies, and the overall rate of TN due to VBA compression was 3.4% (95% CI 2.5–4.3%, p

Purpose of the review Pain in chronic inflammatory joint diseases is a common symptom reported by patients. Pain becomes of absolute clinical relevance especially when it becomes chronic, i.e., when it persists beyond normal healing times. As an operational definition, pain is defined chronic when it lasts for more than 3 months. This article aims to provide a review of the main mechanisms underlying pain in patients with chronic inflammatory joint diseases, discussing in particular their overlap. Recent findings While it may be intuitive how synovial inflammation or enthesitis are responsible for nociceptive pain, in clinical practice, it is common to find patients who continue to complain of symptoms despite optimal control of inflammation. In this kind of patients at the genesis of pain, there may be neuropathic or nociplastic mechanisms. Summary In the context of chronic inflammatory joint diseases, multiple mechanisms generally coexist behind chronic pain. It is the rheumatologist’s task to identify the mechanisms of pain that go beyond the nociceptive mechanisms, to adopt appropriate therapeutic strategies, including avoiding overtreatment of patients with immunosuppressive drugs. In this sense, future research will have to be oriented to search for biomarkers of non-inflammatory pain in patients with chronic inflammatory joint diseases.

Simple Summary Intrahepatic cholangiocarcinoma is a rare disease with increasing incidence and mortality still characterized by an insufficient clinical outcome. Growing attention has recently surrounded this disease, and liver transplantation has emerged as a novel curative treatment for cholangiocarcinoma, along with a better understanding of genetic alterations potentially capable of driving tumorigenesis. The aim of this paper is to present a clinical description of our case series of patients affected by intrahepatic cholangiocarcinoma and by mixed forms of hepatocellular and cholangiocellular carcinoma, together with a genomic profiling of mutations occurring in a panel of genes relevant to solid tumor cancer investigations. Mutations were observed in genes activating signaling pathways known to be involved in intrahepatic cholangiocarcinoma tumorigenesis; a strong association was observed between mutation in genes involving the Notch signaling pathway and tumor size (point-biserial rhopb = 0.93). Abstract Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive primary liver tumor, characterized by a range of different clinical manifestations and by increasing incidence and mortality rates even after curative treatment with radical resection. In recent years, growing attention has been devoted to this disease and some evidence supports liver transplantation (LT) as an appropriate treatment for intrahepatic cholangiocarcinoma; evolving work has also provided a framework for better understanding the genetic basis of this cancer. The aim of this study was to provide a clinical description of our series of patients complemented with Next-Generation Sequencing genomic profiling. From 1999 to 2021, 12 patients who underwent LT with either iCCA or a combined hepatocellular and cholangiocellular carcinoma (HCC-iCCA) were included in this study. Mutations were observed in gene activating signaling pathways known to be involved with iCCA tumorigenesis (KRAS/MAPK, P53, PI3K-Akt/mTOR, cAMP, WNT, epigenetic regulation and chromatin remodeling). Among several others, a strong association was observed between the Notch pathway and tumor size (point-biserial rhopb = 0.93). Our results are suggestive of the benefit potentially derived from molecular analysis to improve our diagnostic capabilities and to devise new treatment protocols, and eventually ameliorate long-term survival of patients affected by iCCA or HCC-iCCA.

In critically ill patients with liver disease, vitamin D deficiency is associated with higher disease severity, increased frequency of infections, and worse outcomes. This study sought to describe the trend of vitamin D in orthotopic liver transplantation (OLT) recipients and its association with outcomes.Prospective observational study of 67 consecutive OLT recipients enrolled between September, 2016 and August, 2017 at IRCCS-ISMETT, Palermo (Italy). Trend of vitamin D levels and potential factors influencing it levels were evaluated through a generalized linear mixed regression model.Sixty-four (95.5%) recipients were vitamin D deficient (20 ng/ml), with a median value of 8.8 ng/ml [6.2-12.9], and forty-seven of these (70.1%) showed severe deficiency (12 ng/ml) at baseline, 7.9 ng/ml [5.4-8.9]. The baseline vitamin D showed an inverse correlation with liver disease severity: Child-Pugh, MELD score, bilirubin, INR, and organ failure (p 0.01) at baseline. Vitamin D increased on postoperative day (POD) 28 compared with POD1: +4.5 ng/ml, C.I. 95% 3.6-5.3 ng/ml, p 0.01. Lower baseline vitamin D, donor age, transfusion of fresh frozen plasma (negative impact, all p 0.05), and intra-operative bypass (positive impact at POD 28, p 0.01) were associated with variation of vitamin D levels after transplantation. Incomplete graft recovery was associated with lower vitamin D on POD28: 8.2 ± 4.4 versus 13.8 ± 9.4 ng/ml, p 0.01; the odds ratio (OR) was 0.84; CI 95% 0.73-0.97, p = 0.014. The OR for infections within POD 28 was inversely associated with baseline vitamin D: 0.87; CI 95% 0.79-0.98, p = 0.02, and with vitamin D level at baseline12 ng/ml: OR 6.44; CI 95% 1.66-24.94; p 0.01.Preoperative Vitamin D is correlated with disease severity, and was highly associated with invasive infection in the first 28 PODs. After OLT, the value on POD 28 had a strong association with graft function.

Objectives To measure with US the intima-media thickness (IMT) of temporal (superficial, parietal and frontal branches) and axillary arteries in subjects without a diagnosis of GCA and/or PMR with different cardiovascular (CV) risk; and to assess the performance of previously proposed cut-off values for normal IMT. Methods Subjects ≥ 50 years without a diagnosis of GCA or PMR were included. Bilateral US of the temporal arteries, including the frontal and parietal branches, and axillary arteries was performed by two sonographers using a 10–22 MHz and 6–18 MHz probe. The following previously proposed cut-offs were considered: superficial temporal artery: 0.42 mm; frontal branch: 0.34 mm; parietal branch: 0.29 mm; axillary artery: 1.0 mm. Results A total of 808 arteries in 101 subjects were evaluated; of these, 31 (30.7%) were classified as very high CV risk, seven (6.9%) as high, 34 (33.7%) as moderate and 29 (28.7%) as low risk. Subjects with very high or high risk showed higher IMT than those with moderate or low risk in the superficial temporal arteries [0.23 (s.d. 0.07) vs 0.20 (s.d. 0.04), P < 0.01] and in the axillary arteries [0.54 (s.d. 0.17) vs 0.48 (s.d. 0.10), P = 0.002] . The IMT was higher than the reference cut-off in 13/808 (1.6%) arteries, in ≥1 artery in 10/101 subjects (10.1%). Of these 10 subjects, 8 (80%) were classified as having very high or high risk. Conclusion Our results suggest that CV risk might influence the US-determined IMT of the temporal and axillary arteries in subjects without GCA. Therefore, in patients with suspected GCA, particular attention should be paid when measuring the IMT in those patients with very high/high CV risk.

Objective Various studies have shown that overweight and obesity are central features of FM, but the real impact of a high BMI on clinical severity in patients with FM is still controversial. The aim of this study was to analyse the relationships between BMI categories and measures of symptom severity and functional impairment using data from a Web-based registry of patients with FM. Methods Adult patients with an ACR 2010/2011 diagnosis of FM underwent a complete physical examination and laboratory tests and were asked to complete a package of questionnaires covering their sociodemographic and treatment details, in addition to the following disease-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status questionnaire (ModFAS) and the Polysymptomatic Distress Scale (PDS). Results A total of 2339 patients were recruited and divided into two weight categories, underweight/normal (U/N, n = 1127, 48.2%) and overweight/obese (O/O, n = 1212, 51.8%). The total and subscales of FIQR, ModFAS and PSD scores were significantly higher in the O/O patients, as were all the mean scores of the individual FIQR items (P Conclusion Our findings demonstrate that O/O patients with FM are significantly more impaired than U/N patients in all the symptomatological and functional domains as measured using the FIQR, ModFAS and PDS, thus suggesting that being O/O has an additional effect on symptoms and function.

Objective To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. Methods Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: ‘In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?’—which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. Results The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th–75th percentiles) were respectively 61.16 (41.16–77.00), 27.00 (19.00–32.00) and 19.0 (13.00–24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0–23 for remission, 24–40 for mild disease, 41–63 for moderate disease, 64–82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0–12 for remission, 13–20 for mild disease, 21–28 for moderate disease, 29–33 for severe disease and >33 for very severe disease; PDS: 0–5 for remission, 6–15 for mild disease, 16–20 for moderate disease, 21–25 for severe disease and >25 for very severe disease. Conclusions Disease severity cut-offs can represent an important improvement in interpreting FM.

Technique, indications and outcomes of laparoscopic splenectomy in stable trauma patients have not been well described yet. All hemodynamically non-compromised abdominal trauma patients who underwent splenectomy from 1/2013 to 12/2017 at our Level 1 trauma center were included. Demographic and clinical data were collected and analysed with per-protocol and an intention-to-treat comparison between open vs laparoscopic groups. 49 splenectomies were performed (16 laparoscopic, 33 open). Among the laparoscopic group, 81% were successfully completed laparoscopically. Laparoscopy was associated with a higher incidence of concomitant surgical procedures (p 0.016), longer operative times, but a significantly faster return of bowel function and oral diet without reoperations. No significant differences were demonstrated in morbidity, mortality, length of stay, or long-term complications, although laparoscopic had lower surgical site infection (0 vs 21%).The isolated splenic injury sub-analysis included 25 splenectomies,76% (19) open and 24% (6) laparoscopic and confirmed reduction in post-operative morbidity (40 vs 57%), blood transfusion (0 vs 48%), ICU admission (20 vs 57%) and overall LOS (7 vs 9 days) in the laparoscopic group. Laparoscopic splenectomy is a safe and effective technique for hemodynamically stable patients with splenic trauma and may represent an advantageous alternative to open splenectomy in terms of post-operative recovery and morbidity. Supplementary Information The online version contains supplementary material available at 10.1007/s13304-021-01045-z.

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on practical activities and didactic teaching of residents and fellows. This survey aimed to propose long-term changes for ophthalmology training based on the changes experienced by trainees and their perception of new training opportunities. Methods: An online survey was distributed to ophthalmology trainees in multiple countries. Descriptive statistics were used to analyse the data. Results: A total of 504 analyzable responses were collected from 32 different countries. The current impact of COVID-19 pandemic was described as “severe” by most trainees (55.2%); however, the future perspective was more optimistic as demonstrated by the greater number of responses reporting a presumed “moderate” (37.3%), “mild” (14.1%) or “slight” (4.2%) long-term impact. The vast majority of trainees reported a decrease ≥50% of clinical activity (76.4%) and >75% of surgical activity (74.6%). Although an initial gap in didactic teaching has been experienced by many (55.4%), regular web-based teaching was reportedly attended by 67.7% of the respondents. A strong agreement was found regarding the worthwhile role of web-based case-presentations in clinical training (91.7%), web-based discussion of edited surgical videos (85.7%) and simulation-based practice (86.9%) in surgical training. Conclusions: This survey, focusing on trainees’ perspective, strongly reinforces the need to promptly include new technology-based training tools, such as web-based teaching, virtual surgical simulators, and telementoring, in long-term reorganisation of ophthalmology training to ensure its continuity and effectiveness, which would remain available even in the face of another unpredictable crisis within the health system.

Because of the current limits of immunological tests in the diagnosis of tuberculosis there is a need to identify new and rapid tests that can be carried out on a large scale in endemic countries and useful in the identification of infected subjects, but also able to discriminate those with latent infection from subjects with active. We have taken into consideration and analysed the LIODetect®TB-ST Tuberculosis Rapid Test, a membrane test for the qualitative detection of specific IgG, IgA, and IgM antibodies against Mycobacterium tuberculosis, performed on serum, plasma, or whole blood.85 samples positive to QuantiFERON TB-GOLD PLUS test were processed using this test and the results obtained were concordant with clinical diagnosis.To our knowledge, the LIODetect®TB-ST Tuberculosis Rapid Test is the only test; that identifies active tuberculosis disease with high sensitivity and specificity and its use might be of help in the diagnosis of tuberculosis, especially in endemic countries.

At present, infertility is a key-issue. When applicable, in vitro fertilization (IVF) has become the standard approach to treat this condition but a thorough investigation and, whenever possible, the individual diagnosis of the underlying causes of infertility are required. For many female causes, indeed, efficient medical therapies are available to achieve a fast solution of the problem. This review is based on the relevant literature indexed in PubMed and SCOPUS and is focused on the most recent clinical literature on the treatment of women (and couples) affected from infertility. The reduction in IVF treatment burden and risks are now considered pivotal to set ‘patient-friendly’ therapies and represent crucial issues for both patients and physicians. To this end, the researchers are now focusing their attention on old drugs with new indications and new compounds with more appropriate functions, to improve the compliance of the women and reduce the burden of infertility, a condition that is becoming an important issue in the modern world, also for the Public Health System.

To compare the accuracy of contrast-enhanced MRI using established dimensional and morphological criteria versus integrated [18F]FDG PET/MRI in identifying regional lymph node metastases in patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC). For this purpose, we compare MRI and PET/MRI using the histopathological findings in dissected lymph nodes as the gold standard. We retrospectively reviewed 26 patients with histologically proven HNSCC who underwent gadolinium-enhanced [18F]FDG PET/MRI as part of their staging. All neck lymph nodes were classified on MRI using dimensional and/or morphological criteria. Then, they were jointly assessed by a nuclear medicine physician and a radiologist using integrated [18F]PET/MR images. ROC curves were obtained to compare the techniques. Lymph node histopathology was considered as the reference standard. Out of 865 lymph nodes, 35 were malignant at histopathology (3 with micro-metastases). Sensitivity and specificity were 48.6% and 99.5% for MRI using dimensional criteria; 60.0% and 99.6% for MRI using morphological criteria; 60.0% and 99.4% for MRI using both; and 74.3% and 97.6% for PET using MR as anatomic localization. The area under the ROC curve was higher for PET and MRI localization (0.859) than for MRI using dimensional (0.740; p

Objective: Several symptoms are common to knee osteoarthritis and Baker’s cyst. To what extent each condition contributes to the patient’s discomfort is still a matter of debate. The aim of the present study was twofold: first, to compare the burden of symptoms in patients with isolated knee osteoarthritis and patients with knee osteoarthritis associated with Baker’s cyst; second, to assess the outcomes after conservative treatments. Subject and Methods: Patients suffering from monolateral idiopathic knee osteoarthritis were enrolled. Demographic, anthropometric and clinical data (KOOS scale) were collected. Ultrasound evaluation was performed according to standard protocols. On the basis of the clinical presentation different therapeutic options were used (fluid withdrawal, hyaluronic acid and/or steroids injections). Results: One-hundred and thirty patients were included in the study (97 with isolated knee osteoarthritis, 33 with knee osteoarthritis and Baker’s cyst). In basal conditions, lower scores in KOOS sub-scales were observed in patients with knee osteoarthritis associated with Baker’s cyst and in patients with effusion compared with patients without effusion. At 3 months after therapy significant higher scores were observed in both groups. At 6 months the scores were unchanged in the patients without Baker’s cyst, but worsened in those with Baker’s cyst. Conclusions: The study shows that Baker’s cysts associated with knee osteoarthritis contribute to the burden of symptoms. The conservative treatment of both conditions allows significant improvements, but in the medium term (6 months) the efficacy of the therapy declines in patients with knee osteoarthritis associated with Baker’s cyst.

Background/aim Quality of life (QoL) in early breast cancer (BC) treatment may be affected by acute and late toxicities. This study evaluated the impact of radiotherapy (RT) schedules, treatment-related toxicities, hormone therapy (HT) and age on QoL. Patients and methods Ninety-five patients answered the FACT-B 4.0 questionnaire. Acute or late toxicities were recorded at each follow-up visit. Results The median trend of the QoL subscales was stable during all questionnaires. HT negatively impacted on Functional Assessment of Cancer Therapy-General-Total, functional and emotional wellbeing. No difference was recorded between RT schedules and toxicity. No significant differences for age were detected in QoL. Conclusion RT seems not to influence QoL of BC patients, in terms of fractionation regimen or RT-related side-effects. Moreover, women having systemic HT experienced a QoL worse than patients treated with RT only. Further and long-term protocols are needed to improve the validity of the tool.

Ultrasound (US) is a promising tool for assessing sarcopenia. We aimed to test in the rheumatology setting two US scanning protocols to measure muscle thickness (MT) at the anterior thigh level and to assess their feasibility and reliability. In the first phase of the study, three rheumatologists performed a US examination on 19 consecutive patients adopting two scanning protocols, namely the anterior superior iliac spine (ASIS) and the greater trochanter techniques. After consensus was obtained on the easiest scanning protocol to perform, two rheumatologists adopted only the ASIS technique in 40 consecutive patients. MT measurements were recorded as well as the time needed to complete each scanning protocol bilaterally. The median time needed to complete the US examination was under 5 minutes for each of the two techniques, with no significant difference between them (p = 0.64). In the first phase, we found an excellent inter-observer reliability of the proposed scanning protocols, with a higher but nonstatistically significant intraclass correlation coefficient (ICC) for the ASIS technique compared with the greater trochanter technique (ICC 0.97 vs. ICC 0.92, p = 0.05). The ASIS technique had a significantly higher intra-observer reliability (ICC 0.97 vs. ICC 0.92, p 0.01). In the second phase, the ASIS technique confirmed on a larger sample its excellent inter-observer reliability, with an ICC of 0.96. The present study presents a novel tool for assessing sarcopenia and provides evidence in favor of feasibility and reliability of US measurement of MT at the anterior thigh level in rheumatology setting. Key Points • This study demonstrates that ultrasound (US) measurement of muscle thickness at the anterior thigh level is highly reliable, especially for the "anterior superior iliac spine (ASIS)" technique. • The short time needed to complete the US assessment highlights the feasibility of the proposed scanning protocols. • The simplicity and conciseness of the proposed techniques will allow other researchers and clinicians to use it for a fast assessment of sarcopenia.

Some case reports and small case series of patients with silicone breast implant (SBI) have reported the development of systemic sclerosis (SSc) many years later, despite conflicting evidence of this association in the literature. Recently, patients with SSc and anti-RNA polymerase III antibodies positivity have been associated with previous silicone implants and/or breast cancer, showing clinical features that differ from the classic SSc, such as rapid and diffuse cutaneous involvement and scleroderma renal crisis (SRC). The specific autoimmune reaction is not yet fully understood, although knowledge in this regard is increasing. We describe a case that can support these previous observations, strengthening this association which must be taken into account. Clinicians should be aware of this new clinical entity, given the widespread use of silicone implants.

BACKGROUND/OBJECTIVES Atrial fibrillation (AF) subtypes may carry different cardiovascular risk profiles, but information on their frequency from population-based studies is lacking. We estimated prevalence of AF subtypes in a representative sample of the Italian older population, projecting figures for Italy and the European Union. DESIGN Cross-sectional study. SETTING Three primary care practices in northern, central, and southern Italy. PARTICIPANTS All individuals aged 65 years or older, for a total sample of 6,016 subjects. Excluding 235 noneligible, participation was 78.3%, which left 4,528 participants. MEASUREMENTS A double systematic and opportunistic screening procedure identified possible AF cases, followed by clinical and electrocardiogram confirmation. Patients were categorized with paroxysmal, persistent, or permanent AF. Prevalence was calculated by sex and 5-year age groups. Prevalence figures were applied to population projections for all 28 European Union states to estimate AF subtypes expected in future decades. RESULTS In the 4,528 participants (mean age = 74.5 ± 6.8 years; 47.2% men), 331 AF cases were identified: 140 (42.3%) paroxysmal, 77 (23.3%) persistent, and 114 (34.4%) permanent. Prevalence was 3.1% (95% confidence interval (CI) = 2.6%-3.6%) for paroxysmal, 1.7% (95% CI = 1.4%-2.1%) for persistent, and 2.5% (95% CI = 2.1%-3.0%) for permanent AF. Italian older persons having AF in 2016 were estimated at approximately 449,000 for paroxysmal, approximately 240,000 for persistent, and approximately 391,000 for permanent AF, projected to increase in 2060 to approximately 785,000, approximately 358,000, and approximately 748,000, respectively. European Union older persons having AF in 2016 were estimated at approximately 3,185,000 for paroxysmal, approximately 1,722,000 for persistent, and approximately 2,710,000 for permanent AF, projected to increase in 2060 to approximately 5,989,000, approximately 2,833,000, and approximately 5,579,000, respectively. CONCLUSION We provided first projections of AF subtypes for Italy and Europe. The worse cardiovascular risk profile of persistent and permanent forms indicates an increased burden in future decades.

Purpose Closure of bladder exstrophy is one of the most complex reconstructive procedures. Basic concepts of these operations, as well as their subtle nuances, require years of experience. However, the volume of these cases is low. The authors describe the experience of a junior surgeon learning the details of exstrophy closure during fellowship and her initial career. Methods Fellows graduating in 2014 were surveyed for their exstrophy experience during fellowship and the following four years. Operative logs of the junior faculty member were reviewed during the same time. Average operative times were calculated for each year. Results Seventeen of the 25 fellows responded to the survey. Eight surgeons did one or fewer exstrophy closures during fellowship; 14 did one or fewer closures as an attending. The junior faculty member assisted in 18 closures as a fellow and 48 exstrophy closures during the next four years. Average operative time decreased from 485 to 309 min from attendingship year one to four. Conclusions There are subtle details inside and outside of the operating room required to ensure a successful outcome in this important step of exstrophy reconstruction. Working alongside senior colleagues is essential to allow the junior surgeon to ascend this ladder of mastering exstrophy closure. Type of study Diagnostic. Level of evidence V

Background Frailty is a frequent condition in patients with knee osteoarthritis (KOA). However, there are different constructs on how to define it. Survey of Health, Ageing and Retirement in Europe-Frailty Instrument (SHARE-FI) is one of them. Aim To assess the prevalence of frailty, according to the SHARE-FI definition in patients with symptomatic KOA, and to establish its associated factors. Methods Symptomatic KOA patients were evaluated for pain symptoms, quality of life, comorbidities, ongoing drug therapy, and radiological damage. Patients were categorised according to the SHARE-FI definition into frail, pre-frail, and non-frail, and compared to a group of healthy controls associated by age and gender. Results 170 symptomatic KOA patients (76.5% female, mean age 70.1 years) and 186 healthy controls were included. According to SHARE-FI criteria, 35 patients (20.6%) were categorised frail, 50 (29.4%) pre-frail, and 85 (50%) non-frail. The prevalence of frail or pre-frail subjects was statistically significantly higher in patients with symptomatic KOA. Stratifying the patients according to the frailty categories, frail subjects showed significantly higher mean values of pain. The results from logistic regression analysis revealed that polypharmacy (p = 0.003), pain (p = 0.016) and comorbidities (p = 0.035) were the variables independently associated with frailty in symptomatic KOA. Discussion Frailty or pre-frailty, defined by SHARE-FI, is common in symptomatic KOA. The main factors associated with frailty were polypharmacy, pain and comorbidity burden. Conclusions SHARE-FI can represent an useful tool to define frailty in symptomatic KOA.

Objectives To comparatively assess the sonographic spectrum of carpal tunnel syndrome (CTS) in patients with rheumatoid arthritis (RA) and in patients with idiopathic CTS. Methods Fifty-seven RA patients and 25 idiopathic CTS patients were consecutively enrolled. The diagnosis of CTS in RA patients was made according to clinical history and examination. The following sonographic findings were assessed at carpal tunnel level: median nerve cross-sectional area (CSA) at the carpal tunnel proximal inlet, finger flexor tendons tenosynovitis, radio-carpal synovitis and intraneural power Doppler (PD) signal. Results CTS was diagnosed in 15/57 RA patients (26.3%). Twenty-three RA wrists with CTS, 84 RA wrists without CTS and 34 idiopathic CTS wrists were evaluated. The average CSA of the median nerve was higher in idiopathic CTS than in RA wrists with CTS (17.7 mm2 vs 10.6 mm2, p p = 0.04) and idiopathic CTS (p = 0.02). Intraneural PD signal was more common in CTS (in both RA and idiopathic CTS) wrists compared with wrists without CTS (p Conclusion The sonographic spectrum of CTS in RA patients is characterized by an inflammatory pattern, defined by the presence of finger flexor tendons tenosynovitis and/or radio-carpal joint synovitis. Conversely, a marked median nerve swelling is the dominant feature in idiopathic CTS. Intraneural PD signal is a frequent finding in both conditions. Key Points• Carpal tunnel syndrome (CTS) associated with rheumatoid arthritis (RA) and idiopathic CTS have distinct ultrasound patterns.• The most characteristic sonographic features of CTS in RA patients are those indicative of synovial tissue inflammation at carpal tunnel level. Conversely, marked median nerve swelling is the dominant finding in idiopathic CTS.• Intraneural power Doppler signal is a frequent finding in both conditions.• In patients with CTS, differently from electrophysiology, US can provide clues prompting a rheumatology referral in case of prominent inflammatory findings at carpal tunnel level.

Background The aim of this study was to evaluate and compare the internal and external responsiveness of a computed-aided method (CaM) with a conventional visual reader-based score (CoVR) to measure interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) on high resolution computed tomography (HRCT). Methods Forty-five patients were evaluated in this retrospective cohort. HRCTs were collected at baseline and after 1 year. HRCT abnormalities were evaluated according to a CoVR (Warrick's method) and a quantitative CaM. Internal 1-year responsiveness was tested with a standardized mean response (SRM). Analyses of the receiver operating characteristic curves (ROCs) evaluated the sensitivity and specificity of the two methods to discriminate between clinically relevant progression and no relevant progression, using expert judgment as the gold standard (external responsiveness). Results In one year, lung involvement was stable/improved in 17 of the 45 patients (37.8%) and worsened in 28 patients (62.2%). HRCT scores changed moderately over the follow-up period. Using SFM, CaM was significantly more responsive in detecting changes due to treatment than the CoVR method. Likewise, in the analysis of the ROC curve, CaM scores showed the highest performance (AUC ROC CaM vs. CoVR, 0.951 vs. 0.807; p = 0.0065). Conclusion Quantitative analysis of CaM was more responsive than the CoVR method to accurately evaluate and monitor SSc-ILD progression or response to therapy.

The role of the pediatric urologic surgeon does not end with initial reconstructive surgery. Many of the congenital anomalies encountered require multiple staged operations while others may not involve further surgery but require a life-long follow-up and often revisions. Management of most of these disorders must extend into and through adolescence before transitioning these patients to adult colleagues. The primary goal of management of all congenital uropathies is protection and/or reversal of renal insult. For posterior urethral valves, in particular, avoidance of end-stage renal failure may not be possible in severe cases due to the congenital nephropathy but usually can be prolonged. Likewise, prevention or minimization of urinary tract infections is important for overall health and eventual renal function. Attainment of urinary continence is an important goal for most with a proven positive impact on quality of life; however, measures to achieve that goal can require significant efforts for those with neuropathic bladder dysfunction, obstructive uropathies, and bladder exstrophy. A particular challenge is maximizing future self-esteem, sexual function, and reproductive potential for those with genital anomalies such as hypospadias, the bladder exstrophy epispadias complex, prune belly syndrome, and Mullerian anomalies. Few endeavors are rewarding as working with children and their families throughout childhood and adolescence to help them attain these goals, and modern advances have enhanced our ability to get them to adulthood in better physical and mental health than ever before.

Aim The aims of this prospective study were to determine the dimension of adherence in rheumatoid arthritis (RA) patients receiving subcutaneously administered anti-tumor necrosis factor-α (anti-TNFα) agents and to evaluate the influence of injection site pain and skin perceptions following subcutaneous administration of anti-TNFα drugs on patients' adherence. Method An inception cohort of patients starting subcutaneously administered anti-TNFα treatment was enrolled. Injection site pain perception was assessed through the Self-Injection Assessment Pain Questionnaire (SIAPQ), and adherence to treatment was ascertained by the Compliance Questionnaire for Rheumatology (CQR5). Associations between beliefs and non-adherence, and the influence of demographic (age, disease duration, educational level), clinical (body mass index, patient global assessment, physician global assessment, Numerical Rating Scale of pain, Health Assessment Questionnaire-Disability Index, Simplified Disease Activity Index, and comorbidities measured by the modified Rheumatic Disease Comorbidty Index), and radiographic (Simple Erosion Narrowing Score) variables were assessed using logistic regression models. Results Adherence data over a 12-month interval were available for 193 patients. Of these, 21.7% reported non-adherence to anti-TNFα therapy. No difference (P = .383) was found for anti-TNFα drugs (adalimumab, etanercept, certolizumab pegol and golimumab). In the logistic model, age (P = .0029), higher disease activity (P = .020), low numbers of comorbidity conditions (P = .0004), injection site pain and skin perception (P = .0008), were significantly associated with increased likelihood of medication adherence. Conclusion Adherence is influenced by both demographic characteristics (age) and clinical factors (disease activity, comorbidity burden and injection site pain and skin perception) in RA patients.

Objective To explore a series of classic bladder exstrophy (CBE) cases referred to the authors’ institution where primary closure with penile disassembly epispadias repair was complicated by penile injury. The penile disassembly technique is frequently combined with bladder closure in patients with CBE undergoing the complete primary repair of exstrophy (CPRE). Penile disassembly has been posited as a risk for penile injury by ischemic mechanisms. Methods A prospectively-maintained institutional database of 1337 exstrophy-epispadias complex patients was reviewed for CPRE cases referred to the authors’ institution, and those with injury to the penis were identified. The location, extent of injury, and subsequent management is reported. Triplanar magnetic resonance imaging (MRI) of the pelvis with volumetric analysis was used for penile compartment quantification. Results 131 male CBE patients were referred after prior CPRE. 26 (20%) were identified with penile loss and reviewed. 81% were closed in the neonatal period, and 54% had a pelvic osteotomy. Median follow-up time was 9.9 years (range 0.6-21.3). Of 26 patients with penile loss, 77% had unilateral loss and in 23% had bilateral loss involving the glans and/or one or both corpora cavernosa. MRI of the pelvis confirmed anterior corporal deficiency that resulted from primary closure. Three patients were successfully managed with myocutaneous neophalloplasty. Conclusions Complete penile disassembly during bladder exstrophy closure may lead to penile ischemia. MRI may be used in the assessment of the extent of injury and planning surgical correction. This major complication questions the continued application of complete penile disassembly in the reconstruction of bladder exstrophy.

Breast cancer (BC) mortality is mainly due to metastatic disease, which is primarily driven by cancer stem cells (CSC). The chemokine C-X-C motif ligand-1 (CXCL1) is involved in BC metastasis, but the question of whether it regulates breast cancer stem cell (BCSC) behavior is yet to be explored. Here, we demonstrate that BCSCs express CXCR2 and produce CXCL1, which stimulates their proliferation and self-renewal, and that CXCL1 blockade inhibits both BCSC proliferation and mammosphere formation efficiency. CXCL1 amplifies its own production and remarkably induces both tumor-promoting and immunosuppressive factors, includingSPP1/OPN,ACKR3/CXCR7,TLR4,TNFSF10/TRAILandCCL18and, to a lesser extent, immunostimulatory cytokines, includingIL15, while it downregulatesCCL2,CCL28, andCXCR4. CXCL1 downregulatesTWIST2andSNAI2, while it boostsTWIST1expression in association with the loss of E-Cadherin, ultimately promoting BCSC epithelial-mesenchymal transition. Bioinformatic analyses of transcriptional data obtained from BC samples of 1,084 patients, reveals thatCXCL1expressing BCs mostly belong to the Triple-Negative (TN) subtype, and that BC expression ofCXCL1strongly correlates with that of pro-angiogenic and cancer promoting genes, such asCXCL2-3-5-6,FGFBP1,BCL11A,PI3,B3GNT5,BBOX1, andPTX3, suggesting that the CXCL1 signaling cascade is part of a broader tumor-promoting signaling network. Our findings reveal that CXCL1 functions as an autocrine growth factor for BCSCs and elicits primarily tumor progression and immune escape programs. Targeting the CXCL1/CXCR2 axis could restrain the BCSC compartment and improve the treatment of aggressive BC.

Altered insulin signaling and insulin resistance are considered the link between Alzheimer's disease (AD) and metabolic syndrome. Here, by using an in vitro and an in vivo model, we investigated the relationship between these disorders focusing on neuronal mitochondrial dysfunction and mitophagy. In vitro Aβ insult induced the opening of mitochondrial permeability transition pore (mPTP), mitochondrial membrane potential (ΔΨm) loss, and apoptosis while insulin addition ameliorated these dysfunctions. The same alterations were detected in a 16 weeks of age mouse model of diet-induced obesity and insulin resistance. In addition, we detected an increase of fission related proteins and activation of mitophagy, proved by the rise of PINK1 and Parkin proteins. Nevertheless, in vitro, the increase of p62 and LC3 indicated an alteration in autophagy, while, in vivo decreased expression of p62 and increase of LC3 suggested removing of damaged mitochondria. Finally, in aged mice (28 and 48 weeks), the data indicated impairment of mitophagy and suggested the accumulation of damaged mitochondria. Taken together these outcomes indicate that alteration of the insulin pathway affects mitochondrial integrity, and effective mitophagy is age-dependent.

Background Despite the current therapeutic options for the treatment of inflammatory bowel disease, surgery is still frequently required in the emergency setting, although the number of cases performed seems to have decreased in recent years. The World Society of Emergency Surgery decided to debate in a consensus conference of experts, the main pertinent issues around the management of inflammatory bowel disease in the emergent situation, with the need to provide focused guidelines for acute care and emergency surgeons. Method A group of experienced surgeons and gastroenterologists were nominated to develop the topics assigned and answer the questions addressed by the Steering Committee of the project. Each expert followed a precise analysis and grading of the studies selected for review. Statements and recommendations were discussed and voted at the Consensus Conference of the 6th World Society of Emergency Surgery held in Nijmegen (The Netherlands) in June 2019. Conclusions Complicated inflammatory bowel disease requires a multidisciplinary approach because of the complexity of this patient group and disease spectrum in the emergency setting, with the aim of obtaining safe surgery with good functional outcomes and a decreasing stoma rate where appropriate.

We investigated the contribution of human leukocyte antigen A2 (HLA-A2) and HLA-E-restricted CD8+ T cells in patients with Mycobacterium tuberculosis and human immunodeficiency virus 1 (HIV-1) coinfection. HIV-1 downregulates HLA-A, -B, and -C molecules in infected cells, thus influencing recognition by HLA class I-restricted CD8+ T cells but not by HLA-E-restricted CD8+ T cells, owing to the inability of the virus to downmodulate their expression. Therefore, antigen-specific HLA-E-restricted CD8+ T cells could play a protective role in Mycobacterium tuberculosis and HIV-1 coinfection. HLA-E- and HLA-A2-restricted Mycobacterium tuberculosis-specific CD8+ T cells were tested in vitro for cytotoxic and microbicidal activities, and their frequencies and phenotypes were evaluated ex vivo in patients with active tuberculosis and concomitant HIV-1 infection. HIV-1 and Mycobacterium tuberculosis coinfection caused downmodulation of HLA-A2 expression in human monocyte-derived macrophages associated with resistance to lysis by HLA-A2-restricted CD8+ T cells and failure to restrict the growth of intracellular Mycobacterium tuberculosis. Conversely, HLA-E surface expression and HLA-E-restricted cytolytic and microbicidal CD8 responses were not affected. HLA-E-restricted and Mycobacterium tuberculosis-specific CD8+ T cells were expanded in the circulation of patients with Mycobacterium tuberculosis/HIV-1 coinfection, as measured by tetramer staining, but displayed a terminally differentiated and exhausted phenotype that was rescued in vitro by anti-PD-1 (programmed cell death protein 1) monoclonal antibody. Together, these results indicate that HLA-E-restricted and Mycobacterium tuberculosis-specific CD8+ T cells in patients with Mycobacterium tuberculosis/HIV-1 coinfection have an exhausted phenotype and fail to expand in vitro in response to antigen stimulation, which can be restored by blocking the PD-1 pathway using the specific monoclonal antibody nivolumab.

BACKGROUND CIN2 is considered a biologically equivocal lesion falling between low and high grade cervical dysplasia, but it is often managed with cervical conization as a high-grade lesion. However, since cervical conization can lead to an increased risk of adverse obstetric events, it might be interesting to identify, by colposcopy, a subgroup of women with a low risk of "occult" CIN3 who could be managed with a "wait and see" approach. METHODS All the women with CIN2 cervical biopsy from 1999 to 2019 were retrospectively identified. Their colposcopic patterns at the time of biopsy and the histopathological findings on the final cone specimen were compared. RESULTS Among the 354 women with CIN2 biopsy included, the overall CIN3+ lesion rate on final cone specimen was 21.4%. The rate of CIN3 on final specimen was higher in women with G2 colposcopy compared to G1 (27,2% vs 15.9%, p= 0.01). Among women with G1 colposcopy, the rate of CIN3+ lesions was significantly higher in women with fine punctation (p=0.02) while no differences in women with thin acetowhite epithelium or fine mosaic emerged. CONCLUSIONS In women with CIN2 biopsy, when a G2 pattern or G1 with fine punctation on colposcopy is detected, there is an increased risk of CIN3+ on final histology, therefore an excisional treatment should be preferred. Otherwise, in women with CIN2 biopsy and other G1 patterns on colposcopy, a "wait and see" approach could be considered.

Sexually transmitted infections (STIs) are a serious global health problem. In Italy, data describing the vulnerability to STIs of specific sexual minorities and the influence of sociodemographic and behavioral determinants are limited, as most infections are not subject to mandatory notification. This retrospective study describes the sociodemographic profile and main sexual behaviors of patients attending a hospital in Palermo (Sicily, Italy) from January 2018 to March 2019 as predictors of STI risk. Patients were divided in subgroups: men-who-have-sex-with-men (MSM), men-who-have-sex-with-women (MSW), bisexual men and females. Data were obtained through an anonymous questionnaire. Patients were tested for chlamydia, syphilis, Mycoplasma genitalium infection, genital herpes and HPV infection. A total of 294 subjects with STIs (male/female ratio about 2:1) were screened. Of the total sample, 79.6% of patients were Italian. MSM accounted for 34.3%, MSW for 29.6%, bisexual men for 5.8% and females for 30.3%. A total of 44.5% of patients had a high education level, 42.5% reported irregular use of condoms, 20.7% reported having had 5–10 partners in the six months prior to the visit and 32.9% were HIV-positive. HPV infection and syphilis were the most prevalent STIs. Conclusions: The most common profile of patients attending our clinic was that of an adult, Italian man with a high level of education, poor use of condoms and a high number of partners. MSM had the highest sex-behavior-related risk for STIs. In addition, our results suggest that all STD teams need to implement counselling topics and recommendations to share with patients, as well as tips on how to approach sexual health education/counselling, thereby promoting patient-centered approaches and educational programs.

Funder: Università degli Studi di Trieste, PURPOSE: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. METHODS: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). RESULTS: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51-6.90 for PFS and HR 3.41, CI 1.47-7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31-4.51 for PFS and HR = 2.40, 95% CI: 1.19-4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone. CONCLUSIONS: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.

Background Global variations in survival for brain tumors are very wide when all histological types are considered together. Appraisal of international differences should be informed by the distribution of histology, but little is known beyond Europe and North America. Methods The source for the analysis was the CONCORD database, a program of global surveillance of cancer survival trends, which includes the tumor records of individual patients from more than 300 population-based cancer registries. We considered all patients aged 0-99 years who were diagnosed with a primary brain tumor during 2000-2014, whether malignant or nonmalignant. We presented the histology distribution of these tumors, for patients diagnosed during 2000-2004, 2005-2009, and 2010-2014. Results Records were submitted from 60 countries on 5 continents, 67 331 for children and 671 085 for adults. After exclusion of irrelevant morphology codes, the final study population comprised 60 783 children and 602 112 adults. Only 59 of 60 countries covered in CONCORD-3 were included because none of the Mexican records were eligible. We defined 12 histology groups for children, and 11 for adults. In children (0-14 years), the proportion of low-grade astrocytomas ranged between 6% and 50%. Medulloblastoma was the most common subtype in countries where low-grade astrocytoma was less commonly reported. In adults (15-99 years), the proportion of glioblastomas varied between 9% and 69%. International comparisons were made difficult by wide differences in the proportion of tumors with unspecified histology, which accounted for up to 52% of diagnoses in children and up to 65% in adults. Conclusions To our knowledge, this is the first account of the global histology distribution of brain tumors, in children and adults. Our findings provide insights into the practices and the quality of cancer registration worldwide.

Pregnancy related transient osteoporosis of the hip (PR-TOH) is a rare condition that manifests with sudden pain located in the groin region, anterior thigh and buttocks. It is a benign and in the majority of cases self-limiting disease, related to bone marrow oedema. It occurs during the third trimester of pregnancy or less frequently during the post-partum period. Hip movements are usually restricted by pain and it often becomes a non-obstetric indication for Caesarean delivery. Here, we report a case of unilateral PR-TOH diagnosed by magnetic resonance imaging (MRI) and a literature review.

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.

Objective: To evaluate concordance between prenatal and postnatal diagnosis of congenital talipes equinovarus (cTEV), rates of surgery and postnatal outcomes in relation to the prenatal classification of severity. Study design: This is a retrospective observational cohort study on fetuses with a prenatal diagnosis of cTEV between 2004 and 2018. All cases of isolated cTEV in singleton pregnancies were included. Postnatally, the Ponseti method was applied. Children were followed-up postnatally for at least two years, with a specific focus on neurodevelopmental outcome. Results: The cohort included 81 fetuses with a prenatal diagnosis of cTEV confirmed postnatally in 86.4% of cases. Concordance between prenatal and postnatal assessment was good for both laterality and degree of severity (k = 0.61 and 0.66, respectively). The average Pirani score, number of casts and rates of Achilles tendon tenotomy were higher for III degree cTEV (p < 0.001). Within this group only, the rate of relapse was 11% and the rates of major surgery was 6%. The postnatal outcome was normal in 68.6% newborns, while 14% of cases had a diagnosis of minor additional findings and 17% had an impairment of neurological development. None of the outcome was statistically correlated to the prenatal assessment of laterality or degree. Conclusions: The accuracy of prenatal ultrasound for isolated cTEV is 86% with a false positive diagnosis of 14%. The grade of cTEV assigned prenatally correlates to postnatal severity and longer orthopedic rehabilitation in terms of number of casts and need of surgery. The assessment of the correlation between cTEV and neurological impairment requires further prospective studies on larger cohorts.

IntroductionClinical presentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in old adults from Southern Italy is little known. This study aims to investigate the mortality risk related to risk factors, therapy and clinical course and to suggest prognostic indicators based on day-to-day follow-up of clinical and laboratory findings.Material and methodsIt was designed as a retrospective longitudinal cohort study of adult SARS-CoV-2 patients admitted at Partinico COVID Hospital in Palermo, Southern Italy. Patients were recruited between 4 March and 25 April and followed up until 31 May 2020, day-to-day until death or hospital discharge. Clinical data, laboratory tests and treatment data were extracted from medical records and epidemiologic information was obtained by clinical history and the medical interview.ResultsForty-seven patients (median age = 75 IQR: 59.50–86.00) were followed up during a 87 days observation period, accounting for a total of 1,035 person days. At the end of follow-up, 28 (60%) patients were discharged and 19 (40%) died, so that the estimated incidence density rate was 0.018 deaths per day (18 SARS-CoV-2-related deaths per 1,000 patient days). Diabetes (HR = 8.13, 95% CI: 1.91–34.67), chronic kidney failure (HR = 5.86, 95% CI: 1.36–25.21), dementia (HR = 7.84, 95% CI: 1.80–34.20), and neutrophil/lymphocyte ratio > 7 (HR = 10.37, 95% CI: 2.24–48.14) were found as significant prognostic factors.ConclusionsThe joint evaluation of dementia, diabetes, chronic kidney failure and neutrophil/lymphocyte ratio showed an optimal prognostic value already in the first week of follow-up. The day-to-day follow-up provides essential information for clinical monitoring and treatment of the disease in a hospital setting and improves the disease’s home management, especially for older patients with frailty.

Background: Aphanizomenon flos-aquae (AFA) is a unicellular cyanobacterium considered to be a &ldquo, superfood&rdquo, for its complete nutritional profile and beneficial properties. We investigated possible beneficial effects of an AFA extract, commercialized as AphaMax&reg, containing concentrated amount of phycocyanins and phytochrome, in 2,4 dinitrobenzensulfonic acid(DNBS)-induced colitis in rats. Methods: Effects of preventive oral treatment of AphaMax&reg, (20, 50 or 100 mg/kg/day) in colitic rats were assessed and then macroscopic and microscopic analyses were performed to evaluate the inflammation degree. Myeloperoxidase (MPO) activity and NF-&kappa, B, pro-inflammatory citockines, cycloxygenase-2 (COX-2), and inducible NOS (iNOS) levels of expression were determined, as Reactive Oxygen Species (ROS) and nitrite levels. Results: AphaMax&reg, treatment attenuated the severity of colitis ameliorating clinical signs. AphaMax&reg, reduced the histological colonic damage and decreased MPO activity, NF-&kappa, B activation, as well as iNOS and COX-2 expression. AphaMax&reg, treatment improved the altered immune response associated with colonic inflammation reducing IL-1&beta, IL-6 expression. Lastly, AphaMax&reg, reduced oxidative stress, decreasing ROS and nitrite levels. Conclusions: Preventive treatment with AphaMax&reg, attenuates the severity of the inflammation in DNBS colitis rats involving decrease of the NF-kB activation, reduction of iNOS and COX-2 expression, and inhibition of oxidative stress. Due its anti-inflammatory and antioxidant proprieties AphaMax&reg, could be a good candidate as a complementary drug in inflammatory bowel disease (IBD) treatment.

Spondylodiscitis is a complex disease whose diagnosis and management are still challenging. The differentiation between infectious and non-infectious aetiology is mandatory to avoid delays in the treatment of life-threatening infectious conditions. Imaging methods, in particular magnetic resonance imaging (MRI), play a key role in differential diagnosis. MRI provides detailed anatomical information, especially regarding the epidural space and spinal cord, and may allow differential diagnosis by assessing the characteristics of certain infectious and inflammatory/degenerative lesions. In this article, we provide an overview of the radiological characteristics and differentiating features of non-infectious inflammatory spinal disorders and infectious spondylodiscitis, focussing on MRI results and presenting relevant clinical and pathological features that help early diagnosis.

Highlights • No data are available to the distress of infertile couples during COVID-19. • Stop performing ART treatments during COVID-19 contributed to increase anxiety. • The psychological impact was more severe for women than for men. • Psychological impact of COVID-19 in infertility couple should not be underestimated., Objective(s) to evaluate the impact of the COVID-19 pandemic on infertile couples’ emotions, anxiety and future plans. Study Design An observational study was perfomed by Italian ART centers and online forums. In this study, infertile couples candidate to ART and whose treatment was blocked due to the COVID-19 lockdown were enrolled through an online survey. The psychological impact of COVID-19 was measured by Impact of Event Scale-Revised (IES-R) and by a short form of the Spielberger State-Trait Anxiety Inventory (STAI); Self-perceived anxiety related either to pregnancy safety and to economic crisis measured by VAS scale. Results 627 patients completed the survey. The COVID-19 lock-down had a moderate/severe psychological impact on infertile patients (mean IES-R score 36.4 ± 16.6). The mean STAI score was 49.8 ± 15.3, with an overall incidence of STAI > 36 of 71%. The mean VAS scale for anxiety perception was 45.3 ± 15.3. Women were more emotionally distressed, anxious and depressed than men (36.8 ± 16.4 vs 31.0 ± 18.4 for IES-R, respectively; p = 0.03). Notwithstanding the uncertainty about pregnancy safety, 64.6% of respondents chose to maintain their reproductive programme. Economic crisis induced 11.5% of the surveyed patients to give up their ART program. Respondents who had at least one relative affected by COVID-19 had a significantly higher IES-R score and anxiety VAS, but not higher STAI scores, than patients belonging to unaffected families. Conclusion(s) COVID-19 pandemic itself and the recommendation to stop ART program generated higher distress levels in infertile couples. The psychological impact of COVID-19 pandemic in infertility patients should not be underestimated, and a specific psychological support should be planned.