Prognostic value of scalp EEG ictal patterns in epilepsy surgery of hippocampal sclerosis.

BACKGROUND: Temporal lobe epilepsy associated with hippocampal sclerosis (TLE-HS) is a surgically treatable epileptic syndrome. While the core of pre-surgical evaluations rely on video-EEG, recent studies question the necessity of recorded seizures denying a possible role of ictal EEG in surgical decision. This study aims to retrospectively assess the prognostic value of EEG ictal patterns in TLE-HS, in order to identify which patients need further investigations before offering surgery. METHODS: We included TLE-HS patients who underwent surgery with at least one captured seizure during non-invasive pre-surgical video-EEG recordings. They were classified in "mesial" and "lateral/mixed", according to the ictal EEG patterns, defined by the frequency of the discharge (mesial ≥ 5 Hz, lateral < 5 Hz). Seizure outcome was assessed by Engel's Class. Statistical analyses were performed to evaluate associations between EEG patterns and post-surgical outcomes. RESULTS: Sixty-nine exhibited a mesial pattern, forty- two displayed lateral/mixed patterns. Mesial pattern group had a significantly higher rate of postsurgical seizure freedom (82.7% vs. 28.6%). Gender, age of onset, age at surgery, duration of epilepsy, seizure frequency, and lateralization did not influence the outcome. Mesial pattern significantly correlated with favorable outcomes (p < 0.001), suggesting its potential predictive value. CONCLUSION: This retrospective study proposes ictal EEG patterns as possible predictors of postoperative prognosis in TLE-HS. A mesial pattern correlates with better outcomes, indicating a potentially more circumscribed epileptogenic zone. Patients with lateral/mixed patterns may benefit from additional investigations to delineate the epileptogenic zone. Further studies are warranted to validate and extend these findings.

Impact of liver fibrosis on COVID-19 in-hospital mortality in Southern Italy.

BACKGROUND & AIMS: SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects. METHODS: This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3. RESULTS: At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3). CONCLUSIONS: FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

Parasagittal Meningiomas: The Impact of Sinus Opening and Grade of Resection on Clinical Outcome and Recurrence in a Consecutive Series of Patients.

BACKGROUND: Surgical management of parasagittal meningiomas (PMs) remains controversial in the literature. The need to pursue a resection as radical as possible and the high risk of venous injuries contribute to making the sinus opening a widely argued choice. This study aimed to analyze factors affecting the risk of recurrence and to assess clinical outcomes of patients who underwent surgical resection of PMs with conservative or aggressive management of the intrasinusal portion. METHODS: A single-institution retrospective review of all patients with PM surgically treated between January 2013 and March 2021 was conducted. RESULTS: Among 56 patients, the sinus was opened in 32 patients (57%), and a conservative approach was used in 24 patients (43%). The sinus opening was found to be a predictive factor of radical resection (Simpson grade [SG] I-II) (P = 0.007). SG was the only predictive factor of recurrence (P < 0.001). The radical resection group (SG I-II) showed recurrence-free survival at 72 months of about 90% versus 30% in the non-radical resection group (SG III-IV) (log-rank test = 14.21, P < 0.001). Aggressive management of the sinus and radical resection were not found to be related to permanent deficit (P = 0.214 and P = 0.254) or worsening of Karnofsky performance scale score (P = 0.822 and P = 0.933). CONCLUSIONS: Removal of the intrasinusal portion of the tumor using standard procedures is not associated with a higher risk of permanent deficit or worsening of Karnofsky performance scale and reduces the risk of recurrence.

Fasting duration impacts ribosome protein 6 phosphorylation in zebrafish brain: New insights in aquatic organisms' welfare.

BACKGROUND: Short- or mid-term fasting, full or partial, triggers metabolic response known to have in turn health effects in an organism. At central level, the metabolic stimulus triggered by fasting is known to be perceived firstly by hypothalamic neurons. In the field of neuroscience, ribosomal protein S6 (S6) phosphorylation is commonly used as a readout of the mammalian target of rapamycin complex 1 signalling activation or as a marker for neuronal activity. The aim of this study is addressed to evaluate whether the phosphorylation of S6 occurs in the central neurons of zebrafish exposed to four (short-term) and seven (mid-term) days of complete fasting. METHODS: Group-housed adult zebrafish were exposed to four and seven days of complete food withdrawal. At the end of the experimental period, Western blotting analyses were carried out to measure the expression levels of the phosphorylated S6 (pS6) by comparing the two experimental conditions versus the control group. The same antibody was then used to identify the distribution pattern of pS6 immunoreactive neurons in the whole brain and in the taste buds. RESULTS: We did not observe increased pS6 levels expression in the brain of animals exposed to short-term fasting compared to the control, whereas the expression increased in brain homogenates of animals exposed to mid-term fasting. pS6 immunoreactivity was reported in some hypothalamic neurons, as well as in the dorsal area of telencephalon and preoptic area, a neurosecretory region homolog to the mammalian paraventricular nucleus. Remarkably, we observed pS6 immunostaining in the sensory cells of taste buds lining the oral epithelium. CONCLUSIONS: Taken together, our data show that in zebrafish, differently from other fish species, seven days of fasting triggers neuronal activity. Furthermore, the immunostaining on sensory cells of taste buds suggests that metabolic changes may modulate also peripheral sensory cells. This event may have valuable implications when using zebrafish to design metabolic studies involving fasting as well as practical consequences on the animal welfare, in particularly stressful conditions, such as transportation.

A Study of Alternative TrkA Splicing Identifies TrkAIII as a Novel Potentially Targetable Participant in PitNET Progression.

Pituitary neuroendocrine tumors (PitNETs) are generally benign but comprise an aggressive, invasive, therapy-resistant, metastatic subset, underpinning a need for novel therapeutic targets. PitNETs exhibit low mutation rates but are associated with conditions linked to alternative splicing, an alternative oncogene pathway activation mechanism. PitNETs express the neurotrophin receptor TrkA, which exhibits oncogenic alternative TrkAIII splicing in other neuroendocrine tumors. We, therefore, assessed whether TrkAIII splicing represents a potential oncogenic participant in PitNETs. TrkAIII splicing was RT-PCR assessed in 53 PitNETs and TrkA isoform(s) expression and activation were assessed by confocal immunofluorescence. TrkAIII splicing was also compared to HIF1α, HIF2α, SF3B1, SRSF2, U2AF1, and JCPyV large T antigen mRNA expression, Xbp1 splicing, and SF3B1 mutation. TrkAIII splicing was detected in all invasive and most non-invasive PitNETs and was significantly elevated in invasive cases. In PitNET lineages, TrkAIII splicing was significantly elevated in invasive PIT1 PitNETs and high in invasive and non-invasive SF1 and TPIT lineages. Immunoreactivity consistent with TrkAIII activation characterized PitNET expressing TrkAIII mRNA, and invasive Pit1 PitNETs exhibited elevated HIF2α expression. TrkAIII splicing did not associate with SF3B1 mutations, altered SF3B1, SRSF2, and U2AF1 or JCPyV large T antigen expression, or Xbp1 splicing. Therefore, TrkAIII splicing is common in PitNETs, is elevated in invasive, especially PIT1 tumors, can result in intracellular TrkAIII activation, and may involve hypoxia. The data support a role for TrkAIII splicing in PitNET pathogenesis and progression and identify TrkAIII as a novel potential target in refractory PitNETs.

Enhanced Mechanical and Electromechanical Properties of Compositionally Complex Zirconia Zr1-x(Gd1/5Pr1/5Nd1/5Sm1/5Y1/5)xO2-δ Ceramics.

Compositionally complex oxides (CCOs) or high-entropy oxides (HEOs) are new multielement oxides with unexplored physical and functional properties. In this work, we report fluorite structure-derived compositionally complex zirconia with composition Zr1-x(Gd1/5Pr1/5Nd1/5Sm1/5Y1/5)xO2-δ (x = 0.1 and 0.2) synthesized in solid-state reaction route and sintered via hot pressing at 1350 °C. We explore the evolution of these oxides' structural, microstructural, mechanical, electrical, and electromechanical properties regarding phase separation and sintering mechanisms. Highly dense ceramics are achieved by bimodal mass diffusion, composing nanometric tetragonal and micrometric cubic grains microstructure. The material exhibits an anomalously large electrostriction response exceeding the M33 value of 10-17 m2/V2 at room temperature and viscoelastic properties of primary creep in nanoindentation measurement under fast loading. These findings are strikingly similar to those reported for doped ceria and bismuth oxide derivates, highlighting the presence of a large concentration of point defects linked to structural distortion and anelastic behavior, which are characteristics of nonclassical ionic electrostrictors.

Outcome of Epilepsy Surgery in MRI-Negative Patients Without Histopathologic Abnormalities in the Resected Tissue.

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

Impact of Acute Kidney Injury on the COVID-19 In-Hospital Mortality in Octogenarian Patients: Insights from the COVOCA Study.

BACKGROUND AND AIMS: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. METHODS: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. RESULTS: 197 patients were included in the study (median age 83.0 [82.0-87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0-25.0] days. From the multivariable Cox regression analysis, after the application of Sidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan-Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank: <0.0001). CONCLUSIONS: In our investigation, we identified a significant association between AKI and mortality rates among octogenarian patients admitted for COVID-19. These findings raise notable concerns and emphasize the imperative for vigilant monitoring of this demographic cohort.

Clinical and Molecular Characteristics of Gonadotroph Pituitary Tumors According to the WHO Classification.

Since 2017, hormone-negative pituitary neuroendocrine tumors expressing the steroidogenic factor SF1 have been recognized as gonadotroph tumors (GnPT) but have been poorly studied. To further characterize their bio-clinical spectrum, 54 GnPT defined by immunostaining for FSH and/or LH (group 1, n = 41) or SF1 only (group 2, n = 13) were compared and studied for SF1, ßFSH, ßLH, CCNA2, CCNB1, CCND1, caspase 3, D2R, and AIP gene expression by qRT-PCR. Immunohistochemistry for AIP and/or D2R was performed in representative cases. Overall, patients were significantly younger in group 1 (P = 0.040 vs group 2), with a similar trend excluding recurrent cases (P = 0.078), and no significant difference in gender, tumor size, invasion or Ki67. SF1 expression was similar in both groups but negatively correlated with the patient's age (P = 0.013) and positively correlated with ßLH (P < 0.001) expression. Beta-FSH and AIP were significantly higher in group 1 (P = 0.042 and P = 0.024, respectively). Ki67 was unrelated to gonadotroph markers but positively correlated with CCNB1 (P = 0.001) and negatively correlated with CCND1 (P = 0.008). D2R and AIP were strongly correlated with each other (P < 0.001), and both positively correlated with SF1, ßFSH, ßLH, and CCND1. AIP immunopositivity was frequently observed in both groups, with a similar median score, and unrelated to Ki67. D2R immunostaining was best detected with a polyclonal antibody and mostly cytoplasmic. This study indicates that hormone-negative GnPT tend to occur in older patients but do not significantly differ from other GnPT in terms of invasion or proliferation. It also points out the current limits of D2R immunostaining in such tumors.

Post-lithiation: a way to control the ionic conductivity of solid-state thin film electrolyte.

Ionic conductivity is pivotal for solid-state battery performance. While the garnet oxide electrolyte Li7La3Zr2O12 (LLZO) boasts high ionic conductivity due to its distinct crystal structure and lithium-ion mobility, lithium loss during fabrication hampers its potential. In this study, we introduce a method that merges synthesis optimization with a post-lithiation process, enhancing LLZO's ionic conductivity. This approach compensates lithium loss with a gas-phase diffusion process, which stabilizes the cubic LLZO phase and amplifies its ionic conductivity by more than three orders of magnitude compared to electrolytes without post-lithiation. Through our comprehensive experimental procedure, we have conclusively determined that the film deposited at 700 °C and subsequently annealed at 700 °C with LiOH exhibits the highest conductivity, with a notable value of 1.11 × 10-2 S cm-1 at 200 °C. This is a significant boost compared to the as-deposited film (3.54 × 10-6 S cm-1 at 200 °C). Our findings present an additional approach to boosting lithium ion diffusion. The approach employed in this work has the potential to be applicable to films produced through other deposition methods, as it addresses the prevalent issue of lithium loss, a significant barrier to the utilization of lithium-rich thin films.

Identifying brain tumor patients' subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis.

Introduction: Central nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear. Objective: The aim of this pilot study was to identify CNS tumor patients' subtypes based on this information and to test associations with tumor malignancy. Methods: 90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy. Results: Out of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10-3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10-3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026). Discussion: These preliminary data suggest that patients' profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery.

Anatomical landmarks during high-magnification microsurgery for a safe and effective resection of high-grade gliomas: how I do it.

BACKGROUND: Gross total resection, when possible, is the first crucial treatment for high-grade gliomas, as it has been demonstrated to be associated with longer survival. Different intraoperative tools, such as neuronavigation, fluorescent agents, and intra-operative ultrasound, have been developed to help neurosurgeons to extend the resection. METHODS: We describe the high-magnification microsurgery technique used during the first surgical removal for high-grade gliomas. We illustrate the key anatomical "markers" of normal brain parenchyma, which guide the surgery. CONCLUSION: High-magnification microsurgery is an anatomically based approach that allows the identification of key anatomical "markers" of normal brain parenchyma in order to resect high-grade gliomas safely and effectively.

Long-term treatment outcomes of temozolomide-based chemoradiation in patients with adult-type diffuse IDH-mutant grade 2 astrocytoma.

PURPOSE: To report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based chemoradiation. METHODS: One hundred and three patients with histologically proven grade 2 astrocytoma received radiation therapy (RT), 50.4-54 Gy in 1.8 Gy fractions, and adjuvant TMZ up to 12 cycles. Fifty-two patients received RT at the time of tumor progression and 51 in the early postoperative period for the presence of at least one high-risk feature (age > 40 years, preoperative tumor size > 5 cm, large postoperative residual tumor, tumor crossing the midline, or presence of neurological symptoms). Overall survival (OS) and progression-free survival (PFS) were calculated from the time of diagnosis. RESULTS: With a median follow-up time of 9.0 years (range, 1.3-15 years), median PFS and OS times were 9 years (95%CI, 6.6-10.3) and 11.8 years (95%CI, 9.3-13.4), respectively. Median PFS was 10.6 years in the early treatment group and 6 years in delayed treatment group (hazard ratio (HR) 0.30; 95%CI 0.16-0.59; p = 0.0005); however, OS was not significantly different between groups (12.8 vs. 10.4 years; HR 0.64; 95%CI 0.33-1.25; p = 0.23). Extent of resection, KPS, and small residual disease were associated with OS, with postoperative tumor ≤ 1 cc that emerged as the strongest independent predictor (HR: 0.27; 95%CI 0.08-0.87; p = 0.01). CONCLUSIONS: TMZ-based chemoradiation is associated with survival benefit in patients with grade 2 IDH-mutant astrocytoma. For this group of patients, chemoradiation can be deferred until time of progression in younger patients receiving extensive resection, while early treatment should be recommended in high-risk patients.

Prognostic Value of Creatinine Levels at Admission on Disease Progression and Mortality in Patients with COVID-19-An Observational Retrospective Study.

INTRODUCTION: Acute kidney disease and chronic kidney disease are considered conditions that can increase the mortality and severity of COVID-19. However, few studies have investigated the impact of creatinine levels on COVID-19 progression in patients without a history of chronic kidney disease. The aim of the study was to assess the impact of creatinine levels at hospital admission on COVID-19 progression and mortality. METHODS: We performed a multicenter, observational, retrospective study involving seventeen COVID-19 Units in the Campania region in southern Italy. All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction on a naso-oropharyngeal swab, from 28 February 2020 to 31 May 2021, were enrolled in the CoviCamp cohort. RESULTS: Evaluating inclusion/exclusion criteria, 1357 patients were included. Considering in-hospital mortality and creatinine value at admission, the best cut-off point to discriminate a death during hospitalization was 1.115 mg/dL. The logistic regression demonstrated that factors independently associated with mortality were age (OR 1.082, CI: 1.054-1.110), Charlson Comorbidity Index (CCI) (OR 1.341, CI: 1.178-1.526), and an abnormal creatinine value at admission, defined as equal to or above 1.12 mg/dL (OR 2.233, CI: 1.373-3.634). DISCUSSION: In conclusion, our study is in line with previous studies confirming that the creatinine serum level can predict mortality in COVID-19 patients and defining that the best cut-off of the creatinine serum level at admission to predict mortality was 1.12 mg/dL.

Pillars of long-term antiretroviral therapy success.

BACKGROUND: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. METHODS: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. RESULTS: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. CONCLUSIONS: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history.

Prevalence and Epidemiological and Clinical Features of Bacterial Infections in a Large Cohort of Patients Hospitalized for COVID-19 in Southern Italy: A Multicenter Study.

BACKGROUND: The aim of this study was to evaluate the prevalence of bacterial infections and antimicrobial prescriptions in a large cohort of COVID-19 patients and to identify the independent predictors of infection and antibiotic prescription. METHODS: All consecutive patients hospitalized for COVID-19 from March 2020 to May 2021 at 1 of the 17 centers participating in the study were included. All subjects showing a clinical presentation consistent with a bacterial infection with microbiological confirmation (documented infection), and/or a procalcitonin value >1 ng/mL (suspected infection) were considered as having a coinfection (if present at admission) or a superinfection (if acquired after at least 48 h of hospital stay). RESULTS: During the study period, of the 1993 patients, 42 (2.1%) presented with a microbiologically documented infection, including 17 coinfections and 25 superinfections, and 267 (13.2%) a suspected infection. A total of 478 subjects (24.5%) received an antibacterial treatment other than macrolides. No independent predictors of confirmed or suspected bacterial infection were identified. On the contrary, being hospitalized during the second wave of the pandemic (OR 1.35, 95% CI 1.18-1.97, p = 0.001), having a SOFA score ≥3 (OR 2.05, 95% CI 1.53-2.75, p < 0.001), a severe or critical disease (OR 1.66, 95% CI 1.24-2.23, p < 0.001), and a high white blood cell count (OR 1.03, 95% CI 1.004-1.06, p = 0.023) were all independently related to having received an antimicrobial prescription. CONCLUSIONS: Our study reported a high rate of antimicrobial prescriptions despite a limited number of documented or suspected bacterial infections among the large cohort of hospitalized COVID-19 patients.

The impact of COVID-19 pandemic on surgical neuro-oncology: A survey from the Italian society of neurosurgery (SINch).

Background: The COVID-19 pandemic and its impact on hospitals' activity and organization has imposed a vast change in standard neurosurgical oncology practice to accommodate for shifting resources. Aims: This investigation aims to analyse the nationwide capability in reorganizing the surgical neuro-oncological activity during the COVID-19 pandemic to evaluate whether COVID-19-pandemic influenced the surgical management in these patients. Method: A web-based dataset model organized by the Italian Neurosurgical Society (SINCh) was sent to all the Italian neurosurgical departments in May 2021, requesting to report the types and numbers of surgical procedures performed in the pre-pandemic period (from March 9th 2019 to March 9th 2020) compared to the pandemic period (from March 10th 2020 to March 10th 2021). Results: This multicentre investigation included the surgical activity of 35 Italian Neurosurgical Departments in a pre-pandemic year versus a pandemic year. During the COVID period, 699 fewer neuro-oncological patients were operated on than in the pre-COVID period. We noted a slight increase in urgency and a more severe decrease in elective and benign pathology. None of these differences was statistically significant. Surgically treated patients who tested positive for SARS-CoV-2 were 36, of which 11 died. Death was found to be COVID-related only in 2 cases. Conclusion: The reorganization of the Italian Neurosurgical Departments was able to guarantee a redistribution of the CNS tumors during the inter-pandemic periods, demonstrating that patients even in the pandemic era could be treated without compromising the efficacy and safety of the surgical procedure.

Unexpected effects of COVID-19 outbreak: adaption of Anti-Retroviral Therapy (ART) delivery policies improved adherence in a population of People Living With HIV (PLWH).

Background: Adherence to Anti-Retroviral Therapy (ART) is crucial for People Living With HIV (PLWH). In Italy, ART is delivered by Hospital Pharmacies, on a renewable prescription from the hospital physician. The measurement of package-refill (the rate of ART packages actually collected out of those to be collected in order to comply with therapy) is an effective tool to evaluate the adherence.During COVID-19 outbreak, at "D. Cotugno" hospital in Naples, Italy, the ART delivery policies have been adapted, in order to reduce the number of patients' access. We analysed the impact of these changes on the pill-refill of ART in January-August 2020, compared with 2018-2019. Methods: "D. Cotugno" hospital is a mono-specialistic Infectious Diseases hospital, caring for about 2500 PLWH. Since February 2020, the hospital was almost entirely dedicated to COVID-19 patients. All out-patient activities were interrupted, except for those dedicated to HIV/AIDS patients.In this preliminary study we included all patients assigned to one of the three Medical Divisions dedicated to HIV, who were already under treatment since at least 2017. Rate of package-refill was obtained by the Hospital Pharmacy registry, demographic and clinical data were derived from clinical database.During COVID-19, many measures were adopted in order to increase safety of PLWH attending to hospital. Among these, medical prescription validity increased from 4 to 6 months, and number of packages to be collected increased from 2 to 4, adopting a multi-month dispensing strategy.Package-refill is adequate if at least 95% of ART have been actually collected; partial and inadequate if 75%-94% or less than 75% of ART, respectively, have been collected. Package-refill was measured during the first year of COVID-19 (March 2020 - February 2021), compared to the same period in the two years before. Results: A total of 594 PLWH were included. PLWH with optimal pill-refill significantly increased in 2020-21 compared to 2018-2020 (62% vs 55%, p 0.013). Discussion: Due to COVID-19, we would have expected a reduction in ART deliveries. Surprisingly, the opposite occurred. The increase of pill-refill rates may be due to different reasons, but we hypothesized that the adaption of delivery policies, with a higher number of packages allowed to be collected, strongly contributed to this result. This study suggests that multi-month dispensing policies may contribute to the improvement of adherence among PLWH.

Does COVID-19 Vaccination with BNT162b2 Influence HIV-Related Immunological and Virological Markers? Data from 235 Persons Living with HIV at Cotugno Hospital, Naples, Italy: Immune Response After Second and Third Doses, and Influence on Immunovirological Markers.

Few data are available on the impact of COVID-19 vaccination on CD4 counts and HIV-RNA in persons living with HIV (PLWH). We present the data of 235 PLWH who were vaccinated with BNT162b2 in March 2021-February 2022 at the "Cotugno" hospital in Naples. PLWH treated at the "Cotugno" hospital, who were vaccinated at the hospital vaccination center, without prior COVID-19 and for whom immunological/virological data were available in the last 12 months and in the 6 months after vaccination were included. Antispike Ab were available for 187 and 64 PLWH after the second and third doses: PLWH with antispikes >33 binding antibodies units (BAU)/mL increased from 91% to 98%. Antinucleocapsid Ab performed in 147 and 56 patients identified 19 (13%) asymptomatic/paucisymptomatic COVID-19 infections after the second dose and an additional 15 (27%) after the third dose. Immunological/virological data were collected before vaccination (T0), after the second dose (T1), and after the third dose (T2). The absolute number of CD4 increased after the third dose (median 663, 657, and 707 at T0, T1, and T2; p < 0.000 T0 vs. T2). The proportion of patients with HIV-RNA <50 copies/mL increases significantly after the second dose (73%; 85.7%; 87.7%; p < 0.000 T0 vs. T2). The presence of COVID-19 asymptomatic/paucisymptomatic infections (demonstrated by the presence of antinucleocapsid Ab) significantly increases SARS-CoV-2 antispike Ab after second dose, but not after third dose. Asymptomatic/paucisymptomatic COVID-19 infections do not have influence on CD4 cell number and HIV-RNA level. Similarly, the presence of not-controlled HIV-RNA (HIV-RNA >50 copies/mL) does not influence antispike Ab response. According to our data, the response to SARS-CoV2 vaccination is effective in people living with HIV. Vaccination against COVID-19 appears to positively affect immunological and virological levels in people living with HIV.

Key role of microsurgical dissections on cadaveric specimens in neurosurgical training: Setting up a new research anatomical laboratory and defining neuroanatomical milestones.

Introduction: Neurosurgery is one of the most complex surgical disciplines where psychomotor skills and deep anatomical and neurological knowledge find their maximum expression. A long period of preparation is necessary to acquire a solid theoretical background and technical skills, improve manual dexterity and visuospatial ability, and try and refine surgical techniques. Moreover, both studying and surgical practice are necessary to deeply understand neuroanatomy, the relationships between structures, and the three-dimensional (3D) orientation that is the core of neurosurgeons' preparation. For all these reasons, a microsurgical neuroanatomy laboratory with human cadaveric specimens results in a unique and irreplaceable training tool that allows the reproduction of patients' positions, 3D anatomy, tissues' consistencies, and step-by-step surgical procedures almost identical to the real ones. Methods: We describe our experience in setting up a new microsurgical neuroanatomy lab (IRCCS Neuromed, Pozzilli, Italy), focusing on the development of training activity programs and microsurgical milestones useful to train the next generation of surgeons. All the required materials and instruments were listed. Results: Six competency levels were designed according to the year of residency, with training exercises and procedures defined for each competency level: (1) soft tissue dissections, bone drilling, and microsurgical suturing; (2) basic craniotomies and neurovascular anatomy; (3) white matter dissection; (4) skull base transcranial approaches; (5) endoscopic approaches; and (6) microanastomosis. A checklist with the milestones was provided. Discussion: Microsurgical dissection of human cadaveric specimens is the optimal way to learn and train on neuroanatomy and neurosurgical procedures before performing them safely in the operating room. We provided a "neurosurgery booklet" with progressive milestones for neurosurgical residents. This step-by-step program may improve the quality of training and guarantee equal skill acquisition across countries. We believe that more efforts should be made to create new microsurgical laboratories, popularize the importance of body donation, and establish a network between universities and laboratories to introduce a compulsory operative training program.