Into the Un(Known). Unveiling Science's intrinsic Art

Entrerete in un mondo nuovo e quasi astratto, apparentemente innaturale. Sarete circondati da suoni e immagini familiari e allo stesso tempo distanti dalla vostra quotidianità. Gli eventi in cui vi troverete immersi sono comuni nella vita di tutti i giorni, anche se non li riconoscete perché “silenziati”. Sono, infatti, fenomeni che acquistano importanza su scale molto grandi, cosmiche potremmo dire, e in condizioni fisiche incompatibili con la vita umana. A raccontarvi questo meraviglioso mondo sarà la “voce” familiare della luce, la radiazione elettromagnetica prodotta dalle varie sorgenti astrofisiche sparse nell’Universo, il principale canale di comunicazione a disposizione degli astronomi per indagare i più reconditi segreti del Cosmo. La luce, esploratrice instancabile, ci racconta gli scenari in cui è stata generata: esplosioni di Supernovae, materia che cade in un buco nero, brillamenti solari, e molto altro. Fenomeni lontani e misteriosi che sfuggono alla nostra esperienza diretta, ma che da anni sono al centro delle ricerche scientifiche più avanzate. Preparatevi ad entrare nell'ignoto, lasciate che la luce vi mostri l'invisibile

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial

Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population

Elevata espressione di hsp-60 di Chlamydophila pneumoniae su placche aterosclerotiche carotidee a prognosi infausta

Some difficult microorganisms, including Chlamydophila pneumoniae, are associated with the atherosclerotic tissue damage.The aim of this study was to evaluate the employment of culture together molecular techniques in order to define the possible role of C. pneumoniae in the atherosclerotic tissue damage. Atheromatous carotid plaques (ACP) were obtained by endoarterectomies from 10 patients with severe stenosis of the internal carotid artery. Each specimen was divided in three parts: a proximal tract to heart, without stenosis, a medial tract, corresponding to the atheromatous plaque, and a distal tract, above the plaque.Aliquots were employed to perform cultures for C. pneumoniae on Hep - 2 cell line in DMEM. DNA and total RNA were extracted from 50-70 mg. of tissue sample and from Hep - 2 106 cultures to investigate 16S rRNA, momp and hsp60 genes.The PCR and RT-PCR resulted negative for momp gene of C. pneumoniae in all samples. PCR and RT-PCR resulted positive for 16S rRNA or hsp60 genes of C. pneumoniae in the proximal portion of two ACPs with hemorrhagic evolution in two patients, one of which complicated with a retinal tromboembolic outcome. Molecular analyses on C. pneumoniae growing from the cultures are in progress.The DNA and RNA amplification of different portions from ACP seems to be useful to evidence the effective localization of C. pneumoniae in the atheromatous arterial tissue. The highly gene expression of C. pneumoniae hsp60 in a patient with acute hemorrhagic evolution of the carotid plaque may suggest that C. pneumoniae might partecipate in the atherogenesis and induce atherosclerosis complications by inflammatory pathways (activation of cytokines, endothelial factors and matrix-degrading metalloproteinases)

GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (COVITAR study, ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed

FUSE-ML: development and external validation of a clinical prediction model for mid-term outcomes after lumbar spinal fusion for degenerative disease

Background: Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. Methods: Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. Results: Models were developed and integrated into a web-app (https://neurosurgery.shinyapps.io/fuseml/) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59–0.74], back pain (0.72, 95%CI: 0.64–0.79), and leg pain (0.64, 95%CI: 0.54–0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. Conclusions: Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk–benefit estimation, truly impacting clinical practice in the era of “personalized medicine” necessitates more robust tools in this patient population

FUSE-ML: development and external validation of a clinical prediction model for mid-term outcomes after lumbar spinal fusion for degenerative disease

Background: Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. Methods: Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. Results: Models were developed and integrated into a web-app (https://neurosurgery.shinyapps.io/fuseml/) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59–0.74], back pain (0.72, 95%CI: 0.64–0.79), and leg pain (0.64, 95%CI: 0.54–0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. Conclusions: Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk–benefit estimation, truly impacting clinical practice in the era of “personalized medicine” necessitates more robust tools in this patient population

Multicenter external validation of prediction models for clinical outcomes after spinal fusion for lumbar degenerative disease

Background: Clinical prediction models (CPM), such as the SCOAP-CERTAIN tool, can be utilized to enhance decision-making for lumbar spinal fusion surgery by providing quantitative estimates of outcomes, aiding surgeons in assessing potential benefits and risks for each individual patient. External validation is crucial in CPM to assess generalizability beyond the initial dataset. This ensures performance in diverse populations, reliability and real-world applicability of the results. Therefore, we externally validated the tool for predictability of improvement in oswestry disability index (ODI), back and leg pain (BP, LP). Methods: Prospective and retrospective data from multicenter registry was obtained. As outcome measure minimum clinically important change was chosen for ODI with ≥ 15-point and ≥ 2-point reduction for numeric rating scales (NRS) for BP and LP 12 months after lumbar fusion for degenerative disease. We externally validate this tool by calculating discrimination and calibration metrics such as intercept, slope, Brier Score, expected/observed ratio, Hosmer-Lemeshow (HL), AUC, sensitivity and specificity. Results: We included 1115 patients, average age 60.8 ± 12.5 years. For 12-month ODI, area-under-the-curve (AUC) was 0.70, the calibration intercept and slope were 1.01 and 0.84, respectively. For NRS BP, AUC was 0.72, with calibration intercept of 0.97 and slope of 0.87. For NRS LP, AUC was 0.70, with calibration intercept of 0.04 and slope of 0.72. Sensitivity ranged from 0.63 to 0.96, while specificity ranged from 0.15 to 0.68. Lack of fit was found for all three models based on HL testing. Conclusions: Utilizing data from a multinational registry, we externally validate the SCOAP-CERTAIN prediction tool. The model demonstrated fair discrimination and calibration of predicted probabilities, necessitating caution in applying it in clinical practice. We suggest that future CPMs focus on predicting longer-term prognosis for this patient population, emphasizing the significance of robust calibration and thorough reporting

Sex Differences in Patient-rated Outcomes After Lumbar Spinal Fusion for Degenerative Disease

Study design: Heterogeneous data collection via a mix of prospective, retrospective, and ambispective methods. Objective: To evaluate the effect of biological sex on patient-reported outcomes after spinal fusion surgery for lumbar degenerative disease. Summary of Background Data: Current literature suggests sex differences regarding clinical outcome after spine surgery may exist. Substantial methodological heterogeneity and limited comparability of studies warrants further investigation of sex-related differences in treatment outcomes. Methods: We analyzed patients who underwent spinal fusion with or without pedicle screw insertion for lumbar degenerative disease included within a multinational study, comprising patients from 11 centers in 7 countries. Absolute values and change scores (change from pe-operative baseline to post-operative follow-up) for 12-month functional impairment (Oswestry disability index [ODI]) and back and leg pain severity (numeric rating scale [NRS]) were compared between male and female patients. Minimum clinically important difference (MCID) was defined as > 30% improvement. Results: Six-hundred-sixty (59%) of 1115 included patients were female. Female patients presented with significantly baseline ODI (51.5 ± 17.2 vs. 47.8 ± 17.9, P<0.001) and back pain (6.96 ± 2.32 vs. 6.60 ± 2.30, P=0.010) and leg pain (6.49 ± 2.76 vs. 6.01 ± 2.76, P=0.005). At 12-months, female patients still reported significantly higher ODI (22.76 ± 16.97 vs. 20.50 ± 16.10, P=0.025), but not higher back (3.13 ± 2.38 vs. 3.00 ± 2.40, P=0.355) or leg pain (2.62 ± 2.55 vs. .34 ± 2.43, P=0.060). Change scores at 12 months did not differ significantly among male and female patients in ODI (∆ 1.31, 95% CI -3.88-1.25, P=0.315), back (∆ 0.22, 95% CI -0.57-0.12, P=0.197) and leg pain (∆ 0.16, 95% CI -0.56-0.24, P=0.439). MCID at 12-months was achieved in 330 (77.5%) male patients and 481 (76.3%) female patients (P=0.729) for ODI. Conclusion: Both sexes experienced a similar benefit from surgery in terms of relative improvement in scores for functional impairment and pain. Although female patients reported a higher degree of functional impairment and pain preoperatively, at 12 months only their average scores for functional impairment remained higher than those for their male counterparts, while absolute pain scores were similar for female and male patients

Surgical treatment of intraforaminal/extraforaminal lumbar disc herniations: Many approaches for few surgical routes

BACKGROUND: Several disc disease nomenclatures and approaches for LDH exist. The traditional midline bone-destructive procedures together with approaches requiring extreme muscular retraction are being replaced by muscle sparing, targeted, stability-preserving surgical routes. The increasing speculation on LDHs and the innovative corridors described to treat them have lead to an extensive production of papers frequently treating the same topic but adopting different terminologies and reporting contradictory results. METHODS: The review of such literature somehow confounding gave us the chance to regroup by surgical corridors the vast amount of approaches for LDH differently renamed over time. Likewise, LDHs were simplified in intra-foraminal (ILDH), extra-foraminal (ELDH), and intra-/extra-foraminal (IELDH) in relation to precise anatomical boundaries and extent of bulging disc. RESULTS: Through the analysis of the papers, it was possible to identify ideal surgical corridors for ILDHs, ELDHs, and IELDHs, distinguishing for each approach the exposure provided and the technical advantages/disadvantages in terms of muscle trauma, biomechanical stability, and nerve root preservation. A significant disproportion was noted between studies discussing traditional midline approaches or variants of the posterolateral route and those investigating pros and cons of simple or combined alternative corridors. Although rarely discussed, these latter represent valuable strategies particularly for the challenging IELDHs, thanks to the optimal compromise between herniation exposure and bone-muscle preservation. CONCLUSIONS: The integration of adequate mastery of traditional approaches together with a greater confidence through unfamiliar surgical corridors can improve the development of combined mini-invasive procedures, which seem promising for future targeted LDH excisions