Correction: "Nutripiatto": A tool for nutritional education. A survey to assess dietary habits in preschool children.

[This corrects the article DOI: 10.1371/journal.pone.0282748.].

Chronic Suppressive Antibiotic Treatment for Staphylococcal Bone and Joint Implant-Related Infections.

Prosthetic joint infection (PJI) and fracture-related infection (FRI) are difficult-to-treat conditions in patients with severe comorbidity or significant surgical risk. In cases not eligible for standard strategy, debridement procedures with the retention of prosthesis or internal fixation device, combined with long-term antibiotic treatment and subsequent indefinite chronic oral antimicrobial suppression (COAS), can be the only reasonable choice. The aim of this study was to investigate the role of COAS and its follow-up in the management of these cases. We retrospectively analyzed a cohort of 16 patients with a follow-up of at least 6 months (mean age 75 yo, 9F, 7M, 11 PJI, 5 FRI). All microbiological isolates were tetracycline-susceptible staphylococci and for this reason a minocycline-based COAS was adopted after debridement and 3 months of antibiogram-guided antibiotic treatment. Patient monitoring was carried out on a clinical basis, with bimonthly execution of the inflammation indices and serial radiolabeled leukocyte scintigraphy (LS). The overall median time of COAS follow-up was 15 months (min 6-max 30). Moreover, 62.5% of patients were still taking COAS with no relapse after cure at the last evaluation available. Clinical failure with a relapse of the infection was observed in 37.5% of patients; interestingly, 50% of them had previously stopped COAS due to side effects of the antibiotic used. In the COAS follow-up, a combination of clinical, laboratory and LS evaluation seems to monitor the infection properly. COAS can be considered as an interesting approach in patients not suitable for standard treatments of PJI or FRI but it requires careful monitoring.

"Nutripiatto": A tool for nutritional education. A survey to assess dietary habits in preschool children.

Childhood obesity is a global public health concern linked to metabolic and psychological comorbidities. There is growing evidence that children's lifestyle habits are shifting towards obesity, with dire consequences for their future well-being and healthcare costs. In this interventional study, we enrolled 115 children aged between 4-5 years (53% females and 47% males) and carried out nutrition education interventions to improve their dietary habits. We introduced "Nutripiatto", a visual plate icon and easy guide, which was used by the children during the study. We investigated the children's dietary habits using a Food Frequency Questionnaire at the beginning and end of the study, after one month of using "Nutripiatto". The results showed that the children significantly increased the portion sizes and frequency of vegetable consumption (P<0.001) and reduced the consumption of several junk foods such as French fries and crisps (P<0.001), reaching the recommended dietary allowances and frequency of consumption. Daily consumption of water also significantly increased, reaching the suggested amount of six glasses per day. Based on these results, "Nutripiatto" can be considered an effective visual guide and helpful tool to achieve small changes and empower families to make healthier food choices. It can also be considered an effective educational tool for nutritionists and healthcare professionals to improve children's dietary behavior.

Role of Protopine and Nuciferine in the Management of Nocturia, Urgency, and Dysuria in Pre- and Postmenopausal Women: A Prospective Pilot Study.

OBJECTIVES: Nocturia was commonly treated with drugs burdened with high costs and numerous side effects; in fact, more than 70% of patients drop out of long-term treatment. Protopine and nuciferine are two alkaloids that have different effects on the neurotransmitter receptors involved in the regulation mechanism of the onset of urinary stimuli. The aim of the study was to evaluate the efficacy in controlling primarily nocturia and secondarily urgency and dysuria after 3 months of treatment with combination therapy of protopine and nuciferine syrup. DESIGN: This is a prospective cohort study in which all patients were diagnosed with overactive bladder syndrome (OAB) and the presence of the following symptoms: nocturia, urgency, and dysuria. Thirty patients were administered 10 mL/die (16.6 mg of nuciferine, 0.09 mg of protopine) of syrup for 3 months. Patients were evaluated at baseline (T0) with the International Consultation on Incontinence Questionnaire (ICIQ), Visual Analogue Scale (VAS) for the evaluation of dysuria, Patient Perception of Intensity of Urgency Scale (PPIUS) and at 3 months (T1) with the Patients' Global Impression of Change (PGI-C) scale, PPIUS, VAS, and ICIQ. PARTICIPANTS: Women with diagnosis of OAB; the presence of nocturia, urgency, and dysuria symptoms agreeing to undergo treatment and compiling informed consent; and the absence of contraindications to the use of active ingredients were included in the study. SETTING: Patients were recruited at T0 during the visit to the Uro-Gynecology clinic of the University of "Campus Bio-Medico" and visited again 3 months (T1) after the initiation of therapy. METHODS: We explored survey data by descriptive statistics: in particular, continuous values (i.e., ICIQ) have been summarized by mean and standard deviation of discrete ordinal values (i.e., VAS, PPIUS, and bladder diary parameters at T0 and T1) by median, minimum, and maximum reported scores. Where we could assume normality in distribution, assessed by the Shapiro-Wilk test and the evaluation of the QQ plot, we compared the observation of T0 and T1 with the paired Student's t test; otherwise, we tested differences in distribution with the paired Mann-Whitney U test. RESULTS: Thirty patients completed a 3-month therapy. The ICIQ and VAS questionnaires for the assessment of dysuria, both, reported an improvement in dysuria at T1 (p < 0.001). The PPIUS questionnaire reported an improvement in urinary urgency at T1 (p < 0.001). The PGI-C scale in T1 indicated an improvement in symptoms: 93% for nocturia, 70% for urinary urgency, and 63% for dysuria. LIMITATIONS: The weaknesses of this study are the small number of patients; as a pilot study, the study design was not randomized with a placebo and without blinding; and the short follow-up. CONCLUSIONS: Protopine and nuciferine can be an interesting alternative to primarily treat and reduce nocturia episodes, in addition to improving OAB-related urgency and dysuria.

C-reactive protein "at first sight": Standard postoperative trend in gynecological surgery and a comparative analysis with white blood cell levels.

OBJECTIVE: There is a lack of information about the normal trend of C-reactive protein (CRP) blood levels in the postoperative days after gynecological benign surgery. We investigated the impact of different surgical techniques on CRP trend. We performed a comparative analysis between a CRP and white blood cell (WBC) trend in postoperative monitoring. METHODS: We studied 207 surgical patients for benign gynecological pathology. We analyzed CRP and WBC levels after surgery in the total number of women and separately by approaches. RESULTS: CRP mean log scores showed a typical behavior. Moreover, results from chi-square test underline that the proportion of women with this result is independent from the type of surgery they underwent. Log score mean values of CPR differed between all groups and between times. No difference in the mean number of white cells between the second and the third day was found, as observed for CRP. CONCLUSIONS: Our study shows a trend reference model in postoperative monitoring of patients with benign gynecological surgery. The comparative analysis between the CRP and WBC trend in the postoperative days provided us data demonstrating the superiority of CRP in postsurgical patient outcomes monitoring.

Colorectal cancer risk of flat low-grade dysplasia in inflammatory bowel disease: a systematic review and proportion meta-analysis.

BACKGROUND: To date, the optimal management of patients with inflammatory bowel disease (IBD) and flat low-grade dysplasia (fLGD) of the colon or rectum remains controversial. METHODS: A systematic review was reported in accordance with PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Patients diagnosed with fLGD on surveillance endoscopy were pooled from studies published between 2000 and 2020. Advanced neoplasia was defined by the presence of HGD, CRC or small bowel adenocarcinoma detected on subsequent surveillance endoscopy or from examination of resection specimens. We estimated the pooled annual incidence rate of colorectal cancer (CRC) and advanced neoplasia, and the risk factors associated with neoplastic progression. RESULTS: We identified 24 articles and 738 IBD patients were diagnosed with fLGD on endoscopy. Two hundred thirty-six patients (32%) underwent immediate surgery with surgical specimens demonstrating CRC in 8 patients (pooled prevalence, 8.66%; 95% CI 3.58-19.46) and HGD (high grade dysplasia) in 11 patients (pooled prevalence, 13.97%; 95% CI 5.65-30.65). Five hundred-two patients (68%) underwent endoscopic surveillance with 63 patients with fLGD progressing to advanced neoplasia during endoscopic surveillance (38 HGD, 24 CRC and one patient developing small bowel adenocarcinoma). The mean duration of follow-up after fLGD diagnosis was 71 months (10.9-212). The pooled incidence of CRC and advanced neoplasia was 0.5 (95% CI 0.23-0.77) and 1.71 per 100 patient-year (95% CI 0.88-2.54) respectively. The use of corticosteroids and location of fLGD in the distal colon were significantly associated with neoplastic progression. CONCLUSIONS: This study provides a summary incidence rate of CRC and advanced neoplasia in patients with IBD and fLGD to inform surgeons' and endoscopists' decision-making thus reducing potential ineffective treatments.

Health-related quality of life in survivors of severe COVID-19 infection.

BACKGROUND: Long-term effects of Coronavirus Disease 2019 (COVID-19) are increasingly recognized as having a significant impact on Health-Related Quality of Life (HRQoL). Understanding HRQoL status for each patient affected by long COVID-19 and its determinants may have a key role to prevent and treat this condition. METHODS: In this prospective observational study conducted in a large academic COVID-19 hospital in Rome, participants were contacted 2 years after hospital admission for severe COVID-19. To assess HRQoL, EQ-5D-5L and Visual analog scale (EQ VAS) standard questionnaires were administered by interview. Logistic regression model was used to the five health dimensions as dependent variables (0 = no problem, 1 = some/extreme problem). KEY RESULTS: In 137 enrolled patients, the mean pre-COVID and post-COVID EQ-5D-5L index and EQ-VAS score were 0.97 (SD 0.06), 0.79 (SD 0.26) and 72.38 (SD 15.18), respectively. After subdivision of the participants for clinical and social variables, the EQ-5D-5L index resulted significantly lower than in the pre-COVID-19 period. Female gender, unemployed status, and chronic comorbidities were the most common predictors for having any problems in each EQ-5D-5L domain, while also older age and higher Body Mass Index (BMI) showed to be related to a lower EQ-VAS score. CONCLUSION: HRQoL showed to be still low in patients 2 years after acute severe COVID-19. Given the significant impact of SARS-CoV-2 on long-term chronic symptoms, predictors of poor outcomes must be considered during the acute phase of illness to plan a tailored follow-up path for each patient.

Clinical Impact of Colonization with Carbapenem-Resistant Gram-Negative Bacteria in Critically Ill Patients Admitted for Severe Trauma.

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) have raised concerns as common, frequent etiologic agents of nosocomial infections, and patients admitted to intensive care units (ICUs) present the highest risk for colonization and infection. The incidence of colonization and infection in trauma patients remains poorly investigated. The aim of this study was to assess the risk factors for Carbapenem-resistant (CR)-GNB colonization and the clinical impact of colonization acquisition in patients with severe trauma admitted to the ICU in a CR-GNB hyperendemic country. This is a retrospective observational study; clinical and laboratory data were extracted from the nosocomial infection surveillance system database. Among 54 severe trauma patients enrolled in the study, 28 patients were colonized by CR-GNB; 7 (12.96%) patients were already colonized at ICU admission; and 21 (38.89%) patients developed a new colonization during their ICU stay. Risk factors for colonization were the length of stay in the ICU (not colonized, 14.81 days ± 9.1 vs. colonized, 38.19 days ± 27.9; p-value = 0.001) and days of mechanical ventilation (not colonized, 8.46 days ± 7.67 vs. colonized, 22.19 days ± 15.09; p-value < 0.001). There was a strong statistical association between previous colonization and subsequent development of infection (OR = 80.6, 95% CI 4.5−1458.6, p-value < 0.001). Factors associated with the risk of infection in colonized patients also included a higher Charlson comorbidity index, a longer length of stay in the ICU, a longer duration of mechanical ventilation, and a longer duration of treatment with carbapenem and vasopressors (not infected vs. infected: 0(0−4) vs. 1(0−3), p = 0.012; 24.82 ± 16.77 vs. 47 ± 28.51, p = 0.016; 13.54 ± 15.84 vs. 31.7 ± 16.22, p = 0.008; 1.09 ± 1.14 vs. 7.82 ± 9.15, p = 0.008). The adoption of MDR-GNB colonization prevention strategies in critically ill patients with severe trauma is required to improve the quality of care and reduce nosocomial infections, length of hospital stay and mortality.

Rates and Determinants of Hospital-Acquired Infection among ICU Patients Undergoing Cardiac Surgery in Developing Countries: Results from EMERGENCY'NGO's Hospital in Sudan.

Introduction. Knowledge of local and regional antimicrobial resistance (AMR) is crucial in clinical decision-making, especially with critically ill patients. The aim of this study was to investigate the rate and pattern of infections in valvular heart disease patients admitted to the intensive care unit (ICU) at the Salam Centre for Cardiac Surgery in Khartoum, Sudan (run by EMERGENCY NGO). Methods. This is a retrospective, observational study from a single, large international referral centre (part of a Regional Programme), which enrolled patients admitted to the ICU between 1 January and 31 December 2019. Data collected for each patient included demographic data, operating theatre/ICU data and microbiological cultures. Results. Over the study period, 611 patients were enrolled (elective surgery n = 491, urgent surgery n = 34 and urgent medical care n = 86). The infection rate was 14.2% and turned out to be higher in medical than in surgical patients (25.6% vs. 12.4%; p = 0.002; OR = 2.43) and higher in those undergoing urgent surgery than those undergoing elective (29.4% vs. 11.2%; p = 0.004; OR = 3.3). Infection was related to (a) SOFA score (p < 0.001), (b) ICU length of stay (p < 0.001) and (c) days from ICU admission to OT (p = 0.003). A significant relationship between the type of admission (elective, urgent surgery or medical) and the presence of infections was found (p < 0.001). The mortality rate was higher among infected patients (infected vs. infection-free: 10.3% vs. 2.1%; p < 0.001; OR = 5.38; 95% CI: 2.16−13.4; p < 0.001). Conclusions. Hospital-acquired infections remain a relevant preventable cause of mortality in our particular population.

Early Mini-Invasive Treatment of Persistent Cervical Dysplasia: Clinical Outcome and Psycho-Relational Impact.

Introduction: After the diagnosis of L-SIL, 77. 3% had a persistent infection and anomalous Pap Test results. Many of these patients had highlighted psychological consequences such as anxiety, hypochondria, fear of cancer, and sexual problems. Several studies suggested that the clearance of HR-HPV infection could be accelerated by cervical excisional procedures, especially in L-SIL. In consideration of the psychological implications for HPV infection and related dysplasia in patients with CIN1 at PAP-smear and HR-HPV positivity at least for 6 months, we decided to plan a prospective study where we tried to anticipate excisional cervical using a minimally invasive treatment: thin loop electrosurgical excision procedure (t-LEEP). This study aims to analyze the clearance of HR-HPV after 6 and 12 months, clinical outcomes related to t-LEEP, and the psycho-relational impact at 12 months after t-LEEP. Materials and Methods: We enrolled patients with the diagnosis of L-SIL at PAP-smear and HR-HPV positivity with a persistent CIN 1 (at least for 6 months), confirmed by cervical biopsy. All enrolled patients underwent t-LEEP. We followed prospectively and performed for all patients the HPV DNA test at 6 (T1) and 12 months (T2) and STAI-Y and FSFI scores at T0 and T2. Results: We prospectively enrolled 158 patients, 22 are excluded for the established criteria. Patients with HR-HPV and CIN 1 lesions treated with t-LEEP had an overall clearance of 83.8% at T2. In subgroups analysis at T2, we had a regression: in smoker 71.8%, in contraceptive users 69.5%, in patients aged <25 years 100%, aged 25-30 years 85%, aged 30-35 years 94.4%, aged 35-40 years 92%, and aged ≥40 years 89.1%, in HPV-16 96.4%, in HPV-53 89.5%, in HPV-18 87.5%, in HPV-31 86.6%, and in coinfected 3.5%. STAI-Y and FSFI after t-LEEP (T2) were statistically significant, reducing anxiety status and improving sexual function. Conclusion: Based on these results, the use of t-LEEP in patients with persistent CIN 1 and HPV-HR at least for 6 months could be useful for accelerating HPV-HR clearance, in particular, for a subpopulation patient with an increased risk of progression and/or patients with psychological and sexual consequences of carrying an HR-HPV infection.

HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.

AIDS-defining cancers declined after combined antiretroviral therapy (cART) introduction, but lymphomas are still elevated in HIV type 1 (HIV-1)-infected patients. In particular, non-Hodgkin's lymphomas (NHLs) represent the majority of all AIDS-defining cancers and are the most frequent cause of death in these patients. We have recently demonstrated that amino acid (aa) insertions at the HIV-1 matrix protein p17 COOH-terminal region cause protein destabilization, leading to conformational changes. Misfolded p17 variants (vp17s) strongly impact clonogenic B cell growth properties that may contribute to B cell lymphomagenesis as suggested by the significantly higher frequency of detection of vp17s with COOH-terminal aa insertions in plasma of HIV-1-infected patients with NHL. Here, we expand our previous observations by assessing the prevalence of vp17s in large retrospective cohorts of patients with and without lymphoma. We confirm the significantly higher prevalence of vp17s in lymphoma patients than in HIV-1-infected individuals without lymphoma. Analysis of 3,990 sequences deposited between 1985 and 2017 allowed us to highlight a worldwide increasing prevalence of HIV-1 mutants expressing vp17s over time. Since genomic surveillance uncovered a cluster of HIV-1 expressing a B cell clonogenic vp17 dated from 2011 to 2019, we conclude that aa insertions can be fixed in HIV-1 and that mutant viruses displaying B cell clonogenic vp17s are actively spreading.

Assessment of core and support functions of the communicable disease surveillance system in the Kurdistan Region of Iraq.

Early detection and prompt response are crucial measures to prevent and control outbreaks. Public health agencies, therefore, designed the Communicable Disease Surveillance System (CDSS) to obtain essential data instantaneously to be used for appropriate action. However, a periodic evaluation of CDSS is indispensable to ensure the functionality of the system. For this reason, this study aims to assess the performance of the core and support functions of the CDSS in the Kurdistan Region of Iraq. A descriptive cross-sectional study was used. From a total of 291 health facilities HFs (Primary health care centers and Hospitals) in the Kurdistan region of Iraq that have surveillance activities, 74 HFs were selected using a random stratified sampling approach. The World Health Organization (WHO) generic questionnaire has been used to interview the surveillance staff, together with direct collection of the data. Our analysis shows a lack of surveillance guiding manual in the HFs. Even at the district level, where a surveillance manual existed, case definitions, thresholds, and control measures were still missing. To note, more than 93% of HFs had organized and comprehensive patients registers for the collection of their clinical and secondary data. Also, all HFs had functioning laboratories. The majority of them (almost 93%) were equipped to collect, process, and store blood, stool, and urine specimens. About 72% of these laboratories were also able to transport timely the specimens to more specialized laboratories. At all levels, data reporting to the higher level exceeded the recommended minimum rate of 80%. The reporting system at the district level was based on emails, while in the periphery on hand-delivered in paper-based formats (50%), telephone (22%), and social media (22%). Furthermore, our analysis highlights the lack of data analysis: only 3.8% of Primary Health Care Centers conduct simple data analysis regularly, while hospitals do not do any sort of analysis. Also, only a few HFs investigated an outbreak, though using system routine sources to capture these public health events. Our findings show a lack in epidemic preparedness (3%), in feedback (53%), in standard guidelines, training, supervision, and resource allocations in HFs (0%). Taken together, our data show the importance of strengthening the CDSS in the Kurdistan region of Iraq, by reinforcing the surveillance system with continuous feedback, supervision, well-trained and motivated staff, technical support, and coordination between researchers and physicians.

SARS-CoV-2 Among Migrants Recently Arrived in Europe From Low- and Middle-Income Countries: Containment Strategies and Special Features of Management in Reception Centers.

Despite the "migrants and COVID-19" topic has been neglected since felt marginal concerning other aspects of the SARS-CoV-2 pandemic, it represents a relevant public health issue in the European countries. This report describes COVID-19 containment strategies adopted in a large Italian reception center hosting recently arrived asylum-seeker migrants. Risk assessment and prevention measures adopted were described. Geo-spatial epidemiological analysis of the outbreak was reported. Significant gaps in the knowledge of self-protection measures from contagious diseases and in the perception of the pandemic risk were observed in migrants; health promotion activities, targeted to remove cultural barriers and improve behaviors appropriate to individual protection, were able to fulfill this gap. In low-resource settings, especially in closed communities, the implementation of social distancing strategies, the systematic use of individual protection devices, and active syndromic surveillance are essential tools to limit the risk of outbreaks. In the event of an outbreak, it is relevant to rapidly activate containment procedures based on systematic screening, isolation, and quarantine, taking into consideration the limits of tracing contacts within a closed community. Not being able to trace certain contacts, the geo-spatial epidemiological analysis of cases distribution could be key in the management of the outbreak. Interestingly, positive cases identified in our facility were all clinically pauci-symptomatic or asymptomatic. Dedicated strategies are needed to minimize the chance of SARS-CoV-2 transmission in a limited space such as reception centers and a vulnerable population such as migrants.

SARS-CoV-2 shifting transmission dynamics and hidden reservoirs potentially limit efficacy of public health interventions in Italy.

We investigated SARS-CoV-2 transmission dynamics in Italy, one of the countries hit hardest by the pandemic, using phylodynamic analysis of viral genetic and epidemiological data. We observed the co-circulation of multiple SARS-CoV-2 lineages over time, which were linked to multiple importations and characterized by large transmission clusters concomitant with a high number of infections. Subsequent implementation of a three-phase nationwide lockdown strategy greatly reduced infection numbers and hospitalizations. Yet we present evidence of sustained viral spread among sporadic clusters acting as "hidden reservoirs" during summer 2020. Mathematical modelling shows that increased mobility among residents eventually catalyzed the coalescence of such clusters, thus driving up the number of infections and initiating a new epidemic wave. Our results suggest that the efficacy of public health interventions is, ultimately, limited by the size and structure of epidemic reservoirs, which may warrant prioritization during vaccine deployment.

SARS-CoV-2 Lineages and Sub-Lineages Circulating Worldwide: A Dynamic Overview.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan, China, in early December 2019 has rapidly widespread worldwide, becoming one of the major global public health issues of the last centuries. Key Messages: Over the course of the pandemic, due to the advanced whole-genome sequencing technologies, an unprecedented amount of genomes have been generated, providing invaluable insights into the ongoing evolution and epidemiology of the virus during the pandemic. Therefore, this large amount of data played an important role in the SARS-CoV-2 mitigation and control strategies. Key Messages: The active monitoring and characterization of the SARS-CoV-2 lineages circulating worldwide is useful for a more specific diagnosis, better care, and timely treatment. In this review, a concise characterization of all the lineages and sub-lineages circulating and co-circulating across the world has been presented in order to determine the magnitude of the SARS-CoV-2 threat and to better understand the virus genetic diversity and its dispersion dynamics.

Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection.

Respiratory and gastrointestinal symptoms are the predominant clinical manifestations of the coronavirus disease 2019 (COVID-19). Infecting intestinal epithelial cells, the severe acute respiratory syndrome coronavirus-2 may impact on host's microbiota and gut inflammation. It is well established that an imbalanced intestinal microbiome can affect pulmonary function, modulating the host immune response ("gut-lung axis"). While effective vaccines and targeted drugs are being tested, alternative pathophysiology-based options to prevent and treat COVID-19 infection must be considered on top of the limited evidence-based therapy currently available. Addressing intestinal dysbiosis with a probiotic supplement may, therefore, be a sensible option to be evaluated, in addition to current best available medical treatments. Herein, we summed up pathophysiologic assumptions and current evidence regarding bacteriotherapy administration in preventing and treating COVID-19 pneumonia.

Role of BRCA Mutation and HE4 in Predicting Chemotherapy Response in Ovarian Cancer: A Retrospective Pilot Study.

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in BRCA mutated patients and in BRCA wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to BRCA mutation test, patients were further divided into BRCA wild-type (53 patients), and BRCA mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence < 12 months). Thus, in the total population, HE4 performed as a marker of chemosensitivity with a sensibility of 79% and a specificity of 97%. In the BRCA WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the BRCA WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the BRCA mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the BRCA mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios.

Evolution patterns of SARS-CoV-2: Snapshot on its genome variants.

An acute respiratory syndrome (COVID-19), caused by a novel coronavirus (SARS-CoV-2) with a high rate of morbidity and elevate mortality, has emerged as one of the most important threats to humankind in the last centuries. Rigorous determination of SARS-CoV-2 infectivity is very difficult owing to the continuous evolution of the virus, with its single nucleotide polymorphism (SNP) variants and many lineages. However, it is urgently necessary to study the virus in depth, to understand the mechanism of its pathogenicity and virulence, and to develop effective therapeutic strategies. The present contribution summarizes in a succinct way the current knowledge on the evolutionary and structural features of the virus, with the aim of clarifying its mutational pattern and its possible role in the ongoing pandemic.