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The international PRECONNECT Phase IIIb study demonstrated safety and efficacy of trifluridine/tipiracil in the management of patients with metastatic colorectal cancer. Post-hoc analyses in a national context are important because of the differences in disease management across countries. Post-hoc safety and efficacy analyses in the PRECONNECT Italian patient subset were conducted. Patients' quality of life was assessed from baseline to end of treatment. In Italy, 161 patients were enrolled. The median age was 64 years, with a performance status of 0–1. The most common hematological drug-related adverse events ≥grade 3 were neutropenia (41.0%) and anemia (13.7%). The median progression-free survival was reached at 3.0 months, with a disease control rate of 28.6%. The Quality of Life Questionnaire Core 30 score improved in 25.4% of the patients. Safety, efficacy and quality of life results confirmed trifluridine/tipiracil as a feasible and favorable treatment option for metastatic colorectal cancer patients.

Colorectal cancer (CRC) represents one of the most frequent malignancies in terms of incidence and mortality, thus representing the third leading cause of cancer death worldwide. In the last decade, few drugs have enriched the treatment landscape of metastatic CRC and have significantly affected prognosis. Unlike other neoplasms, metastatic CRC patients who have exhausted treatment options often still maintain a good performance status. There are many challenges to increasing potential treatment options, notably a better understanding of disease biology and the mechanisms of resistance underlying cancer treatment failure. The development of new drugs for metastatic CRC certainly represents one of the most important challenges in medical oncology. This article discusses the main limitations in the development of new drugs and potential future scenarios. In particular, we addressed three questions: (1) The main limitations of targeted therapy in the treatment of metastatic CRC (mCRC); (2) New target armamentarium that could escape primary and secondary resistance and lead to more personalized mCRC therapy; and (3) Future directions.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Summary Background The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. Methods TRIBE2 was an open-label, phase 3, randomised study of patients aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatment given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov , NCT02339116 . Findings Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1–41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3–21·4) in the experimental group and 16·4 months (15·1–17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63–0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3–4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis). Interpretation Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria. Funding The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann–La Roche.

Mazama gouazoubira is a widely distributed deer in the South American continent. However, studies on its anatomical characteristics are still scarce. The objective of this study was to elucidate the coronary circulation of M. gouazoubira. With this aim, after collecting cadavers on highways, twenty-four hearts injected with latex and preserved in formaldehyde at 10% were dissected. The dissections revealed that all specimens presented left coronary dominance, characterized by the origin of the subsinuous interventricular branch from the circumflex branch of the left coronary artery. The number of ventricular branches originated from branches of the left coronary artery was approximately five times higher than that of the right coronary artery. The occurrence of myocardial bridges was registered in 91.7% of the individuals, with bridges predominating over the paraconal interventricular branch. The mean length of the paraconal interventricular sulcus was significantly higher in males (p = 0.02). The number of atrial branches and ventricular branches, length of myocardial bridges and length of subsinuous interventricular sulcus did not vary significantly between sex. Left coronary dominance and high frequency of myocardial bridges in M. gouazoubira are preponderant anatomical traits also present in different species of Ruminantia suborder. Coronary dominance studies in other South American deer species may confirm the correlation of this trait with the evolutionary history of these animals.

BACKGROUND: In mCRC, CEA is used to monitor response to systemic therapy together with imaging. After the end of induction, no major improvement in tumour shrinkage is expected, and the availability of a marker able to predict progressive disease (PD) versus no-PD might allow avoiding CT scans. METHODS: We pooled data from patients with baseline CEA ≥ 10 ng/mL included in TRIBE and TRIBE2 studies with the aim of identifying a threshold for percent increase of CEA from nadir able to predict PD after the end of the induction therapy. RESULTS: In total, 1178 paired CEA and radiological assessments from 434 patients were included. According to the optimal cut-off determined by ROC, a CEA increase of at least 120% from nadir differentiated between PD and no-PD with a sensitivity of 74% and a specificity of 78%, excluding PD in the 92% of radiological assessments and allowing to avoid the 67% of CT scans. However, CEA cut-off of 120% was not able to detect radiological PD in 26% of cases. In order to mitigate this issue, a different clinically relevant threshold was evaluated based on the best sensitivity cut-off. Therefore, using any CEA increase from nadir as a threshold, the sensitivity grew to 93% and only in the 7% of cases the radiological PD was not detected. CONCLUSIONS: In mCRC with baseline CEA ≥ 10 ng/mL, CEA values can accurately predict PD versus no-PD after the end of the first-line induction therapy.

Watershed infarcts can involve the brainstem, with lesions distributed across the terminal supply from the vertebral and cerebellar arteries. Brain imaging can highlight a comma-shaped lesion at the edge of vertebral and posteroinferior cerebellar artery vascularization territory. Such peculiar MRI lesion shape might suggest a watershed hypoperfusion etiology and direct workup towards causes of hemodynamic impairment, including postural hypotension, cardiac failure, or vertebral artery origin occlusion.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect that occurs in 20% of ovarian cancer patients treated with the combination of carboplatin/paclitaxel (CP). This toxicity is directly correlated with the dose of paclitaxel administered. Several studies have investigated whether different formulations of taxane can induce this side effect at a lower rate, but, unfortunately, no significant improvement was obtained. CIPN can be disabling in the daily lives of patients and can cause dose reduction or early termination of the treatment. Neuropathy can last for months and even years after its onset. Moreover, patients responsive to CP treatment are candidates for a reintroduction of the same drugs when disease relapse occurs, and residual neuropathy can affect the continuation of treatment. There are no approved drugs that mitigate or prevent the onset of CIPN. In this review, we summarize the evidence regarding the incidence of CIPN with different taxane formulations, regimen schedules and prevention systems. In particular, the Hilotherm® Chemo care device is a regional cooling system that lowers the temperature of the hands and feet to reduce the flow of chemotherapy into the capillaries. We used hilotherapy during chemotherapy infusion to prevent the onset of CIPN. Updated data from 44 ovarian cancer patients treated with 6 cycle of CP show that hilotherapy was well tolerated; only two patients (4.5%) stopped hilotherapy because of cold intolerance, and only one patient (2.2%) experienced grade ≥ 2 CIPN.

BACKGROUND The majority of patients with coronavirus disease 2019 (COVID-19) have good prognoses, but some develop a critical illness that can lead to death. Evidence shows severe acute respiratory syndrome is closely related to the induced cytokine storm. Interleukin-6 is a key player; its role in systemic inflammation is well known. AIM To evaluate the effect of tocilizumab (TCZ), an interleukin-6 receptor antagonist, on the outcomes for patients with COVID-19 pneumonia. METHODS PubMed, EMBASE, SCOPUS, Web of Science, MedRxiv, Science Direct, and the Cochrane Library were searched from inception to 9th June 2020 for observational or prospective studies reporting results of hospitalized adult patients with COVID-19 infection treated with TCZ. Effect sizes were reported as odds ratios (ORs) with 95% confidence intervals (CIs), and an OR less than 1 was associated with a better outcome in those treated with TCZ. RESULTS Overall 13476 patients (33 studies; n = 3264 received TCZ) with COVID-19 pneumonia and various degree of severity were included. Outcome was improved with TCZ. In the primary analysis (n = 19 studies reporting data), mortality was reduced in patients treated with TCZ (OR = 0.64, 95%CI: 0.47-0.87; P < 0.01). In 9 studies where risk of death with TCZ use was controlled for other variables mortality was reduced by 57% (OR = 0.43, 95%CI: 0.27-0.7; P < 0.01). Intensive care need (mechanical ventilation) was also reduced (OR = 0.36, 95%CI: 0.14-0.89; P = 0.02). CONCLUSION In COVID-19-infected patients treated with TCZ, outcome may be improved compared to those not treated with TCZ.

Made available in DSpace on 2021-06-25T10:59:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 This study evaluated the persistence of eugenol-containing (PR, Provy) or eugenol-free (RT, Relyx Temp, and TB, Temp Bond) temporary cement residues and its effects on push-out bond strength and dentinal penetration of the self-adhesive resin cement (Relyx U200). Eighty human roots were endodontically treated and post space prepared. Fourty specimens were distributed in four groups (n = 10): Control (CO), without any clinical procedure, PR, RT, and TB, where a metallic post was cemented with one of the temporary cements. After metallic post removal, hemi sections post space were submitted to SEM analysis. Another specimens were distributed in similar groups, but fiberglass post was cemented using Relyx U200 cement and submitted to push-out bond strength and dentinal penetration cement analysis, in post space thirds. SEM analysis were evaluated by Kruskal–Wallis and Dunn tests, while bond strength and dentinal penetration were evaluated by ANOVA One-Way and Tukey test (p

Pancreatic cancer is considered one of the most aggressive cancers, with an increasing incidence in recent years. To date, chemotherapy is still the standard of care for advanced metastatic disease, unfortunately providing only a slight advantage in terms of survival. The molecular and cellular characteristics of pancreatic cancer cells, as well as the cells that characterize the pancreatic tumour microenvironment, are the basis of the mechanisms of resistance to treatment. After progression during first-line treatment, few patients are eligible for second-line treatment due to the loss of performance status. To date, a clear survival advantage has not yet been demonstrated for second-line chemotherapy. Precision medicine could be the key to increasing responses to cancer treatment and finally impacting survival in this difficult-to-treat disease. In this review, we analyze current recommendations in the second-line setting and potential future prospects.

Aim: To help to remove misperception of an appropriate position of trifluridine/tipiracil (FTD/TPI) in the treatment of metastatic colorectal cancer. Materials & methods: The RAND Corporation/UCLA Appropriateness Method was used by a panel of Italian experts to develop recommendations concerning daily practice with FTD/TPI. Forty-three clinical scenarios were discussed in two rounds and the resulting statements were rated as appropriate, uncertain or inappropriate, according to the median score. Results: Several topics were dealt with, covering the profile of eligible patients, therapeutic options beyond the second line, the practice of treatment with FTD/TPI, evaluation and efficacy and toxicity, as well as costs and compliance. Conclusion: FTD/TPI is an important therapeutic resource in refractory metastatic colorectal cancer that combines manageability and safety.

PURPOSE: In patients with stage III colon cancer (CC) whose tumors demonstrate microsatellite instability (MSI), the efficacy of adjuvant fluoropyrimidine (FP) with or without oxaliplatin has not been clearly demonstrated and the prognostic value of MSI remains uncertain. MATERIALS AND METHODS: Individual patient data from the ACCENT database were used to evaluate the effect of FP with or without oxaliplatin on disease-free survival (DFS) and overall survival (OS) among patients with MSI stage III CC and the prognostic value of MSI in patients treated with FP plus oxaliplatin, by stratified Cox models adjusted for demographic and clinicopathological factors. RESULTS: MSI status was available for 5,457 patients (609 MSI, 11.2%; 4848 microsatellite stable [MSS], 88.8%) from 12 randomized clinical trials (RCTs). Oxaliplatin significantly improved OS of MSI patients from the two RCTs testing FP with or without oxaliplatin (n = 185; adjusted hazard ratio [aHR] = 0.52, 95% CI, 0.28 to 0.93). Among the 4,250 patients treated with FP plus oxaliplatin (461 MSI and 3789 MSS), MSI was associated with better OS in the N1 group compared with MSS (aHR = 0.66; 95% CI, 0.46 to 0.95) but similar survival in the N2 population (aHR = 1.13; 95% CI, 0.86 to 1.48; P interaction = .029). The main independent prognosticators of MSI patients treated with FP plus oxaliplatin were T stage (aHR = 2.09; 95% CI, 1.29 to 3.38) and N stage (aHR = 3.57; 95% CI, 2.32 to 5.48). Similar results were observed for DFS in all analyses. CONCLUSION: Adding oxaliplatin to FP improves OS and DFS in patients with MSI stage III CC. Compared with MSS, MSI patients experienced better outcomes in the N1 group but similar survival in the N2 group.

In patients with metastatic colorectal cancer (mCRC) receiving highly active first-line combination treatments, early tumor shrinkage (ETS) and depth of response (DoR) are associated with survival, but their influence on outcomes during maintenance therapy is unknown. The Valentino study showed inferior PFS in 229 RAS wild-type mCRC patients randomized to panitumumab plus FOLFOX followed by maintenance with panitumumab vs. panitumumab + 5-FU/LV.After blinded independent central review of ETS (≥20% reduction of the sum of target lesions) and DoR in patients enrolled in Valentino, the prognostic and predictive role of such parameters was investigated, along with their combination with PRESSING panel (uncommon genomic alterations associated with anti-EGFRs resistance beyond RAS and BRAF).One hundred and ninety-six patients were included (ETS in 132 [67.3%], median DoR: 44.1%). Both ETS and DoR ≥34% were associated with longer mPFS (p = 0.010 and p 0.001) and mOS (p = 0.006 and p 0.001). The PFS benefit of 5-FU/LV added to panitumumab maintenance, reported in the study, was independent from ETS and DoR status (interaction tests NS for both PFS and OS). However, outcomes were extremely poor in patients who received single-agent panitumumab and had no-ETS (mPFS and mOS: 7.7 and 18.7 months) or DoR 34% (mPFS and mOS: 6.5 and 18 months). Combining PRESSING panel ('molecular hyperselection') and response dynamics allowed to stratify both PFS (p 0.001 and p 0.001 for ETS and DoR, respectively) and OS (p 0.001 and p = 0.017 for ETS and DoR, respectively).ETS and DoR allow on-treatment anticipation of outcomes following an anti-EGFR-based strategy planning de-escalation, and poor radiological response may guide enrolment in crossover strategy trials. As in vivo markers of drug sensitivity, ETS and DoR may be integrated with several patient- and tumor-related factors to wisely drive decision-making on upfront treatment duration and intensity.

Background The role of combination chemotherapy has not yet been established in unresectable locally advanced pancreatic cancer (LAPC) lacking dedicated randomized trials. Methods This phase II trial tested the efficacy of Nab-paclitaxel (NAB-P)/Gemcitabine (G) versus G alone. Patients were randomized, 1:1 to G 1000 mg/m2 on days 1, 8 and 15 every 28 days versus NAB-P 125 mg/m2 on days 1, 8 and 15 every 28 days plus G 1000 mg/m2 on days 1, 8 and 15 every 28 days. Disease progression rate after three cycles of chemotherapy was the primary end-point. Progression-free survival (PFS), overall survival (OS) and response rate were secondary end-points. Findings A total of124 patients were enrolled. The study showed a reduction of a progressive disease from 45.6% with G to 25.4% with NAB-P/G (P = 0.01) at 3 months. Noteworthy, at 6 months in the G arm, 35.6% of patients present a metastatic spread versus 20.8% in the NAB/G arm. The response rate was 5.3% in the G arm and 27% in the NAB/G arm. Median PFS was 4 months for the G arm and 7 months for the NAB-P/G arm. Median OS was 10.6 in the G arm and 12.7 months in the NAB-P/G arm. One patient died during treatment with G due to a stroke. Interpretation. NAB-P/G reduced the rate of LAPC patients progressing after three cycles of chemotherapy compared with G, especially in terms of distant relapses. It positively affects PFS. To the best of our knowledge, this is the first randomized trial providing evidence that combination chemotherapy is superior to gemcitabine alone in this setting. ClinicalTrials.gov Identifier NCT02043730 .

Allogenic red blood cell transfusions exert a potential detrimental effect on the survival when delivered to cancer patients undergoing surgery with curative intent. We performed a systematic review and meta-analysis to assess the association between perioperative allogenic red blood cell transfusions and risk of death as well as relapse after surgery for localized solid tumors. PubMed, the Cochrane Library, and EMBASE were searched from inception to March 2019 for studies reporting the outcome of patients receiving transfusions during radical surgery for non-metastatic cancer. Risk of death and relapse were pooled to provide an adjusted hazard ratio with a 95% confidence interval [hazard ratio (HR) (95% confidence interval {CI})]. Mortality and relapse associated with perioperative transfusion due to cancer surgery were evaluated among participants (n = 123 studies). Overall, RBC transfusions were associated with an increased risk of death [HR = 1.50 (95% CI 1.42–1.57), p

Made available in DSpace on 2022-04-29T08:29:40Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-01 Background: The aim of this study was to evaluate the effects of surface treatments with 1% peracetic acid (PA), solution containing 17% EDTA (SmearClear, Kerr Endodontics), solution containing a combination of 17% EDTA with 2% chlorhexidine (QMix, Dentsply Sirona) on the post-space root dentin compared to 2.5% sodium hypochlorite (NaOCl) on bond strength and resin tags length in dentin. Material and Methods: Forty human-canine roots were endodontically treated and the post space was prepared. The specimens were randomised into four groups (n = 10): control - irrigation with 2.5% NaOCl solution, PA - irrigation with 1% PA, SmearClear - irrigation with SmearClear solution, and QMix - irrigation with QMix solution. The fibre posts were cemented using a self-adhesive resin system (Relyx U200, 3M ESPE). After six months, the specimens were cross-sectioned and subjected to push-out and confocal laser microscopy tests. One-way ANOVA and Tukey's tests were used to analyse the data (a= 0.05). Results: PA and QMix presented the highest bond strength values compared to the other groups (p < 0.05). There was no significant difference between the resin tags length in dentin by the groups (p = 0.75). Conclusions: Irrigation of the post space with 1% PA and QMix showed a positive clinical impact on the adhesion between the fiber post and root dentin. However, these materials had no influence on resin tags length in dentin by self-adhesive resin cement. Department of Restorative Dentistry Araraquara School of Dentistry São Paulo State University (UNESP) School of Dentistry Federal University of Para (UFPA) Department of Restorative Dentistry Bauru School of Dentistry University of Sao Paulo (USP) Department of Restorative Dentistry Araraquara School of Dentistry São Paulo State University (UNESP)

The advent of immunotherapy in onco-haematology has represented a kind of revolution that has been able to modify the prognosis of numerous tumours that until recently would have been rapidly lethal. While much is known about the mechanism of action of these drugs, relatively little is known about the factors that represent potential predictors of response and toxicity. Among these factors, the simultaneous administration of antibiotics and/or steroids seems to have a negative impact. Furthermore, several retrospective studies have highlighted the strong link between cancer and gut microbiota, regardless of the tumour site, and how microbiota, playing a key role in the prevention of systemic inflammation at various levels and in the intestinal homeostasis, can be negatively influenced by the dysbiosis caused by antibiotic therapy administered during or in the weeks immediately preceding the start of immunotherapy. Moreover, we assume that the concurrent administration of steroids, which is often necessary in cancer patients, likely results in a deleterious effect on the therapeutic outcomes of immunotherapy. In this review, we will try to clarify the evidence on the possible detrimental effects of antibiotics and steroids, which are currently considered the double enemies of anticancer immunotherapy.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that accounts for ∼20% of ALL cases. Intensive chemotherapy regimens result in cure rates >85% in children and

Cutaneous adnexal carcinoma with apocrine differentiation is a rare neoplasm arising from cutaneous adnexa, especially of the head and neck and trunk region. Because of its rarity, the diagnosis is challenging and often impossible to distinguish from metastatic cutaneous adenocarcinoma of the breast. The standard of care remains surgery for resectable disease. To date, univocal guidelines for metastatic disease are lacking, particularly regarding systemic therapy. We report a clinical case of a patient diagnosed with cutaneous adnexal adenocarcinoma with apocrine differentiation of the left axilla with lymph node and bone metastasis. We started with carboplatin and paclitaxel chemotherapy regimen, with good response. After progression, we performed a next-generation sequencing analysis (by the Foundation One CDx test) to identify genomic alteration in cancer-related genes. We found PIK3CA and KRAS mutations. Due to this result, the patient started a second-line treatment with a personalized therapy including an mTOR inhibitor, everolimus, and, to date, he is still under treatment. To our knowledge, this is the first case of a patient responding both to chemotherapy and to a personalized treatment with an mTOR inhibitor. It is important to support the value of genomic screening in this rare neoplasm.

Made available in DSpace on 2021-06-25T10:35:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Aim: The aim of this study to evaluate the effects of 10% alpha-tocopherol (10AT) or 20% alpha-tocopherol (20AT) incorporation on biological compatibility, pH, and calcium release of calcium hydroxide (CH) paste associated with 2% chlorhexidine digluconate (CHX). Materials and Methods: Four groups were evaluated: CH, CH-CHX, CH-CHX-10AT, and CH-CHX-20AT. For biological compatibility test, polyethylene tubes containing several pastes were implanted in Wistar rats' subcutaneous tissue (n = 28). After 48 h and 7, 14, and 21 days postimplantation, the specimens were removed and subjected to histologic and histomorphometric analysis. The number of inflammatory cells was evaluated. For pH and calcium release analysis, the pastes were placed individually (n = 10) in plastic tubes and immersed in deionized water. The calcium release and pH changes were evaluated in 24 and 48 h and 7, 14, and 21 days. All data were submitted to Kruskal-Wallis test (α = 0.05). Results: Concerning biological compatibility, all materials shown a similar decidual response (P > 0.05). In the first hours, there was as increase in the number of inflammatory cells, inducing an expressive inflammatory response. After 14 days, inflammation reaction decreased and collagen fiber was organized for the tested pastes (P = 0.05). The pH analysis of the groups maintained the same relationship during the different periods evaluated: the CH and CH-CHX groups showed higher values and were similar to each other (P > 0.05), followed by the CH-CHX-10AT and CH-CHX-20 AT groups. Regarding the amount of calcium ions, in the initial (24 hours) and final (21 days) periods, the groups did not present differences between them (P > 0.05). Conclusion: The 10AT or 20AT, as an antioxidant agent, incorporation to CH and 2% CHX paste negatively affected biological and physicochemical properties. Department of Restorative Dentistry School of Dentistry Araraquara Sao Paulo State University - UNESP Department of Basic Sciences Araçatuba Dental School Sao Paulo State University - UNESP Department of Restorative Dentistry School of Dentistry Araraquara Sao Paulo State University - UNESP Department of Basic Sciences Araçatuba Dental School Sao Paulo State University - UNESP

Background FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab has shown to be one of the therapeutic regimens in first line with the highest activity in patients (pts.) with metastatic colorectal cancer (mCRC) unselected for biomolecular alterations. Generally, tumors co-opt the programmed death-1/ligand 1 (PD-1/PD-L1) signaling pathway as one key mechanism to evade immune surveillance. As today, anti-PD-1 monoclonal antibodies are FDA approved only for DNA mismatch repair deficient/microsatellite instability-high (MMRd/MSI-H), which represent only about 5% among all mCRC. Nowadays, there are no data demonstrating anti PD-1 activity in proficient and stable disease (MMRp/MSS). A different target in mCRC is also the Vascular Endothelial Growth Factor A (VEGF-A), which acts on endothelial cells to stimulate angiogenesis. VEGF-A inhibition with bevacizumab has shown to increase the immune cell infiltration, providing a solid rationale for combining VEGF targeted agents with immune checkpoint inhibitors. Based on these evidences, we explore the combination of triplet chemotherapy (FOLFOXIRI) with bevacizumab and nivolumab in pts. with mCRC RAS/BRAF mutant regardless of microsatellite status. Methods/design This is a prospective, open-label, multicentric phase II trial where pts. with mCRC RAS/BRAF mutated, in first line will receive nivolumab in combination with FOLFOXIRI/bevacizumab every 2 weeks for 8 cycles followed by maintenance with bevacizumab plus nivolumab every 2 weeks. Bevacizumab will be administered intravenously at dose of 5 mg/kg every 2 weeks and nivolumab intravenously as a flat dose of 240 mg every 2 weeks. The primary endpoint is the overall response rate (ORR). This study hypothesis is that the treatment is able to improve the ORR from 66 to 80%. Secondary endpoints include OS, safety, time to progression, duration of response. Collateral translational studies evaluate the i) tumor mutational burden, and ii) genetic alterations by circulating free DNA (cfDNA) obtained from plasma samples. The trial is open to enrollment, 9 of planned 70 pts. have been enrolled. Trial registration NIVACOR is registered at ClinicalTrials.gov: NCT04072198, August 28, 2019.

Small cell tumors arise from the neuroendocrine cell system and they are most frequently found in the lung (SCLC). Small cell tumor could occasionally arise in other body sites, such as the cervix, prostate, gastrointestinal tract, and very rarely from other sites. Metastatic SCLC patients present with metastatic disease in 80% of cases, and the metastases typically are reported in brain, liver, lung, and bone; they rarely could be found in the ovary. Differently, primitive small cell carcinoma of the ovary of pulmonary type is a rare and highly aggressive tumor arising from the ovarian cells; no suitable treatment strategy has been established yet. In this paper, we talk about a 72-year-old woman who presented with abdominal bleeding and a large mass in her pelvic region. A primary ovarian carcinoma was suspected, and she underwent hysterectomy with laparoscopic surgery and bilateral oophorectomy, lymph node resection, omentectomy, complementary appendix and sigmoid resection. The postoperative pathologic diagnosis was a differential diagnosis between small cell ovarian carcinoma of the pulmonary type and metastasis of SCLC.

Background:No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III β-tubulin (TUBB3) as biomarker for prognosis and resistance to taxane-based therapy was reported.Methods:We analyzed GC samples of patients enrolled in the Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S), a randomized adjuvant study comparing 5-fluorouracil/leucovorin (5-FU/LV) and docetaxel-based sequential chemotherapy. TUBB3 was quantitated by selected reaction monitoring mass spectrometry and patients were stratified using a threshold of 750 attomoles per microgram (amol/µg). Cox proportional modeling and Kaplan-Meier survival analysis were used to assess the impact of TUBB3 expression on overall survival (OS) and disease-free survival.Results:Patients with TUBB3 protein levels >750 and Conclusions:The quantification of TUBB3 might be considered as a negative predictive biomarker of benefit from taxane-based therapy in GC. Studies are needed to evaluate its role in the neoadjuvant setting.

Neutropenic enterocolitis is a clinical condition characterized by inflammation of the colic mucosa, usually the caecum, associated with bowel wall thickening in patients with compromised immune system due to chemotherapy treatments. It can occur as well in other clinical conditions that lead to immunosuppression. Clinically, patients present with abdominal pain, fever, and neutropenia on blood tests. A number of major and minor criteria have been suggested for the clinical diagnosis of typhlitis. The most sensitive radiological investigation is represented by a computed tomography scan. There are no guidelines for treatment, but some factors may lead the clinician to medical treatments or prompt surgery as the best choice in that particular patient. The most implicated chemotherapeutic regimens are those based on taxanes. Here, we present a clinical case of a young patient with breast cancer and a review of the state of the art of knowledge regarding neutropenic enterocolitis in adult patients undergoing chemotherapy for the treatment of solid tumors.

Background Lombardy was the epicenter in Italy of the first wave of COVID-19 pandemic. To face the contagion growth, from March 8 to May 8 2020, a regional law re-designed the hub-and-spoke system for time-dependent diseases to better allocate resources for COVID-19 patients. Methods We report the reorganization of the major hospital in Lombardy during COVID-19 pandemic, including the rearrangement of its ICU beds to face COVID-19 pandemic and fulfill its role as extended hub for time-dependent diseases while preserving transplant activity. To highlight the impact of the emergently planned hub-and-spoke system, all patients admitted to a COVID-19-free ICU hub for trauma, neurosurgical emergencies and stroke during the two-month period were retrospectively collected and compared to 2019 cohort. Regional data on organ procurement was retrieved. Observed-to-expected (OE) in-ICU mortality ratios were computed to test the impact of the pandemic on patients affected by time-dependent diseases. Results Dynamic changes in ICU resource allocation occurred according to local COVID-19 epidemiology/trends of patients referred for time-dependent diseases. The absolute increase of admissions for trauma, neurosurgical emergencies and stroke was roughly two-fold. Patients referred to the hub were older and characterized by more severe conditions. An increase in crude mortality was observed, though OE ratios for in-ICU mortality were not statistically different when comparing 2020 vs. 2019. An increase in local organ procurement was observed, limiting the debacle of regional transplant activity. Conclusions We described the effects of a regional emergently planned hub-and-spoke system for time-dependent diseases settled in the epicenter of COVID-19 pandemic in Italy.

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years, 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12–218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32–2.15), however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11–0.51, p &lt, 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.

Enhanced surveillance for dengue virus (DENV) infections in Italy has been implemented since 2012, with annual reports from the National Health Institute. In this study, we summarize available evidence on the epidemiology of officially notified DENV infections from 2010–2021. In total, 1043 DENV infection cases were diagnosed, and most of them occurred in travelers, with only 11 autochthonous cases. The annual incidence rates of DENV infections peaked during 2019 with 0.277 cases per 100,000 (95% confidence interval [95% CI] 0.187–0.267), (age-adjusted incidence rate: 0.328, 95% CI 0.314–0.314). Cases of DENV were clustered during the summer months of July (11.4%), August (19.3%), and September (12.7%). The areas characterized by higher notification rates were north-western (29.0%), and mostly north-eastern Italy (41.3%). The risk for DENV infection in travelers increased in the time period 2015–2019 (risk ratio [RR] 1.808, 95% CI 1.594–2.051) and even during 2020–2021 (RR 1.771, 95% CI 1.238–2.543). Higher risk for DENV was additionally reported in male subjects compared with females subjects, and aged 25 to 44 years, and in individuals from northern and central Italy compared to southern regions and islands. In a multivariable Poisson regression model, the increased number of travelers per 100 inhabitants (incidence rate ratio [IRR] 1.065, 95% CI 1.036–1.096), the incidence in other countries (IRR 1.323, 95% CI 1.165–1.481), the share of individuals aged 25 to 44 years (IRR 1.622, 95% CI 1.338–1.968), and foreign-born residents (IRR 2.717, 95% CI 1.555–3.881), were identified as effectors of annual incidence. In summary, although the circulation of DENV remains clustered among travelers, enhanced surveillance is vital for the early detection of human cases and the prompt implementation of response measures.

Simple Summary The status of microsatellite instability (MSI-H) in gastric or gastroesophageal junction cancer (GC/GEJC) patients eligible for radical surgery proved to be prognostic for an improved survival outcome and predictive for poor/no benefit from the combination of adjuvant/peri-operative chemotherapy. MSI-H tumors display a high sensitivity to immunotherapy and exploratory studies showed that a pre-operative treatment with immune-checkpoint inhibitors may achieve elevated rates of pathological complete responses. The ongoing proof-of-concept INFINITY study is aimed at investigating the role of the combo-immunotherapy durvalumab plus tremelimumab as a neoadjuvant or potentially definitive treatment (avoiding surgery in case of complete clinical response) for MSI-H resectable GC/GEJC patients. Abstract In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection.

Spontaneous intracranial hypotension results from a spinal CSF leak and usually presents with orthostatic headache, although acephalgic presentations have anecdotally been reported. The underlying low CSF volume, rarely, leads to serious complications such as cerebral venous thrombosis and coma. We report a patient presenting with cerebral venous thrombosis secondary to acephalgic spontaneous intracranial hypotension. An epidural blood patch was performed; nonetheless, the patient intracracal condition deteriorated to coma and neuroimages showed a deep brain swelling with midbrain distortion, subsequently complicated by intracranial pontine hemorrhage. © 2020, Fondazione Società Italiana di Neurologia.

The COVID-19 pandemic significantly impacted the labor market and multiple aspects of work and workers’ life. The present rapid review analyzes this impact considering the effects that COVID-19 pandemic had on employment and work-related aspects across different age groups. A comprehensive literature search was performed on scientific contributions published between 2019 and March 2021, resulting in 36 papers pertinent to the scope of this review. Findings were grouped according to different topics, all linked to age: occupational risk, implications on the labor market (i.e., job loss and reemployment, job insecurity, turnover intentions and retirement, and healthcare workers’ return-to-work phase), remote work, and key individual and organizational resources and strategies. Overall, the review revealed variability across age groups in the impact this pandemic had on employment and several work-related aspects (i.e., occupational risk, remote work). Findings supported an age-differential effect of normative history-graded events such as the current pandemic, highlighting different responses and consequences depending on workers’ age., International Journal of Environmental Research and Public Health, 18 (10), ISSN:1660-4601, ISSN:1661-7827

Background: In the last decade, a series of analyses failed to identify predictive biomarkers of resistance/susceptibility for anti-angiogenic drugs in metastatic colorectal cancer (mCRC). We conducted an exploratory preplanned analysis of serum pro-angiogenic factors (SErum aNgiogenesis-cenTRAL) in 72 mCRC patients enrolled in the phase II CENTRAL (ColorEctalavastiNTRiAlLdh) trial, with the aim to identify potential predictive factors for sensitivity/resistance to first line folinic acid-fluorouracil-irinotecan regimen (FOLFIRI) plus bevacizumab. Methods: First-line FOLFIRI/bevacizumab patients were prospectively assessed for the following circulating pro-angiogenic factors, evaluated with ELISA (enzyme-linked immunosorbent assay)-based technique at baseline and at every cycle: Vascular endothelial growth factor A (VEGF-A), hepatocyte growth factor (HGF), stromal derived factor-1 (SDF-1), placental derived growth factor (PlGF), fibroblast growth factor-2 (FGF-2), monocyte chemotactic protein-3 (MCP-3), interleukin-8 (IL-8). Results: Changes in circulating FGF-2 levels among different blood samples seemed to correlate with clinical outcome. Patients who experienced an increase in FGF-2 levels at the second cycle of chemotherapy compared to baseline, had a median Progression Free Survival (mPFS) of 12.85 vs. 7.57 months (Hazard Ratio&mdash, HR: 0.73, 95% Confidence Interval&mdash, CI: 0.43-1.27, p = 0.23). Similar results were seen when comparing FGF-2 concentrations between baseline and eight-week time point (mPFS 12.98 vs. 8.00 months, HR: 0.78, 95% CI: 0.46&ndash, 1.33, p = 0.35). Conclusions: Our pre-planned, prospective analysis suggests that circulating FGF-2 levels&rsquo, early increase could be used as a marker to identify patients who are more likely to gain benefit from FOLFIRI/bevacizumab first-line therapy.

O objetivo deste relato de experiência é apresentar a utilização de metodologias ativas mediadas por tecnologia em tempos de pandemia na disciplina Integração Básico-Clínica II do curso de Medicina. A experiência é caracterizada como uma possibilidade de contribuição ao desenvolvimento docente para o mundo pós-pandemia. Em um grupo de cinco professores e 40 estudantes, a disciplina Integração Básico-Clínica II foi adaptada emergencialmente para atividades mediadas por tecnologia. Os conteúdos trabalhados propiciaram a integração dos conhecimentos disciplinares à clínica e trouxeram inúmeros desafios pedagógicos neste momento inédito de como ensinar, aprender e sobreviver a uma pandemia. Em 16 encontros via plataforma institucional foram utilizadas exclusivamente metodologias ativas de ensino-aprendizagem, com estratégias diversificadas. O modelo de aprendizagem virtual não é algo novo, apesar de inédito para esse grupo de discentes e para esta disciplina e seu valor está em possibilitar repensar a educação e seus mecanismos, num extenuante exercício de criatividade para enfrentar novos desafios surgidos decorrentes de situações extremas. A aplicação de metodologias ativas associado ao feedback dos discentes foi imprescindível para a tomada de decisões na continuidade da integração dos conteúdos, levando à construção de uma disciplina agradável e que contribuiu para o processo formativo de todos os envolvidos. O maior aprendizado foi a necessidade de adaptação e criatividade, permitindo contribuições à construção da identidade docente. A práxis foi fortalecida e reinventada, sendo a adaptação e criatividade, atributos considerados necessários para o desenvolvimento docente para o mundo pós-andemia.

Objective: The aim of this in vitro study was to evaluate the antimicrobial effect of five types of non-industrialized and industrialized probiotics on biofilms formed around orthodontic mini-implants. The null hypothesis tested was: there is no difference in the antimicrobial effect between the five types of probiotics tested around orthodontic mini-implants. Methods: For the experiment, 120 mini-implants were immersed for seven days in Staphylococcus aureus solution for biofilm formation, and were subsequently plated in culture medium containing probiotics. The mini-implants were divided into six different groups, according to the probiotic used: G1)Lactobacillus casei; G2)Lactobacillus brevis; G3)Lactobacillus rhamnosus; G4) Lactobacillus from fermented milk Yakult®; G5) Lactobacillus from fermented milk Batavito® and G6) without use of probiotic, as negative control. Qualitative and quantitative analyses of all groups were performed using the CFU (colony forming unit) count. Results: The study showed that groups G4 and G6 did not present antimicrobial activity, in comparison to groups G1, G2, G3, and G5 (p< 0.05), which demonstrated antimicrobial activity. Conclusion: The non-commercial probiotic bacteria, Lactobacillus casei and Lactobacillus rhamnosus, as well as commercially available fermented milk Batavito® presented promising results in the reduction of colonization of mini-implants by S. aureus. Therefore, the null hypothesis was rejected. RESUMO Objetivo: O objetivo do presente estudo in vitro foi avaliar o efeito antimicrobiano de cinco tipos de probióticos não industrializados ou industrializados em biofilmes formados ao redor de mini-implantes ortodônticos. A hipótese nula testada foi: não há diferença no efeito antimicrobiano entre os cinco tipos de probióticos testados em torno dos mini-implantes ortodônticos. Métodos: Para o experimento, as cabeças de 120 mini-implantes foram imersas por sete dias em solução de Staphylococcus aureus para formação de biofilme e, posteriormente, semeadas em meio de cultura contendo probióticos. Os mini-implantes foram divididos em seis grupos diferentes, de acordo com o probiótico utilizado: G1)Lactobacillus casei; G2)Lactobacillus brevis; G3)Lactobacillus rhamnosus; G4) lactobacilos do leite fermentado Yakult®; G5) lactobacilos do leite fermentado Batavito®; e G6) sem uso de probiótico, como controle negativo. As análises qualitativas e quantitativas de todos os grupos foram realizadas usando a contagem de UFCs (unidades formadoras de colônia). Resultados: O estudo mostrou que os grupos G4 e G6 não apresentaram atividade antimicrobiana, em comparação aos grupos G1, G2, G3 e G5 (p< 0,05), os quais demonstraram atividade antimicrobiana. Conclusão: As bactérias probióticas não comerciais, Lactobacillus casei e Lactobacillus rhamnosus, assim como o leite fermentado comercializado, Batavito®, apresentaram resultados promissores na redução da colonização dos mini-implantes por S. aureus. Portanto, a hipótese nula foi rejeitada.

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effects of adjuvant chemotherapy following curative-intent resection of ampullary adenocarcinoma on survival, quality of life, adverse events and toxicity.

Made available in DSpace on 2022-04-29T08:32:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Background: This study evaluated the effects of several epoxy resin-based sealer compositions (AHP, AH Plus; ADS, Adseal; SPL, Sealer Plus) on bond strength and intratubular dentin penetration of the endodontic obturation, in root canal previously treated with calcium hydroxide intracanal medication (CH) and removed by continuous ultrasonic irrigation (CUI). Material and Methods: Forty-five maxillary canines were prepared up to F5 (ProTaper system), filled with CH, coronally sealed, and stored at 37ºC. After 1 week, CH was removed using 2.5% sodium hypochlorite energized by CUI. The specimens were randomly distributed in three groups (n=15) and root canal obturated, according to epoxy-based resin sealer composition (AHP, ADS or SPL). The roots were transversally sectioned in cervical, middle, and apical thirds. In each radicular third, push out bond strength using universal machine and intratubular dentin using confocal laser scanning microscopy (CLSM) and Image J Program were evaluated. Bond strength and intratubular dentin penetration were statistically evaluated by ANOVA one-way and Tukey tests and Kruskal Wallis test, respectively (α = 0.05). Results: In middle and apical thirds, AHP showed higher bond strength values (e0.05). All epoxy resin-based sealers presented similar intratubular dentin penetration, independently of the radicular thirds (p>0.05). Cohesive and mixed failures were predominant in the cervical thirds. In the middle and apical thirds, AHP showed more cohesive type failures, while ADS and SPL showed more adhesive-type failures. Conclusions: AHP has the highest bond strength in middle and apical radicular thirds, after calcium hydroxide intracanal medication removal using continuous ultrasonic irrigation, although intratubular dentin infiltration being similar among epoxy resin-based sealer with several chemical composition. Department of Restorative Dentistry Endodontics and Dental Materials Bauru School of Dentistry University of São Paulo (USP) Department of Restorative Dentistry Araraquara School of Dentistry State University of São Paulo (UNESP) School of Dentistry Federal University of Pará (UFPA) Department of Restorative Dentistry Araraquara School of Dentistry State University of São Paulo (UNESP)

The objective of this in vitro study was to assess the effects of two antioxidants (sodium ascorbate [SA] and alpha-tocopherol [AT]) on the adhesive interface and dentin bond strength immediately after bleaching with 38 % hydrogen peroxide (38HP) in endodontically-treated teeth. Two stages of experimentation were carried out. Bovine incisors were allocated into four groups (n = 10/group for each experiment): NB, non-bleached restored crowns; 38HP, bleached and immediately restored crowns; 38HP-SA, bleached crowns and SA use; and 38HP-AT, bleached crowns and AT use. Hybrid layer length in dentin (μm) and bond strength (MPa) were assessed with confocal microscopy laser and micro-shear bond strength (μSBS) test, respectively. Failure mode was determined by stereomicroscope. Data analysis was performed with analysis of variance (ANOVA) and Kruskal-Wallis, Dunn, Tukey, and Fisher-exact tests (a = 0.05). Higher values of hybrid layer length were observed similarly in the NB and 38HP-SA groups. The highest μSBS mean values were observed in the NB group (18 .51 ? 1.33), whereas the SBS values for 38HP-AT (1.68 ? 0.32) were similar to the 38HP group (1.61 ? 0.51) (p > 0.05) and significantly lower than the 38HP-SA group (5.78 ? 0.71). Adhesive failures were predominant in the 38HP and 38HP-AT groups. Cohesive and mixed failures were mostly observed in the NB and 38HP-SA groups, respectively. In conclusion, AT has no immediate effect on the hybrid layer formation and μSBS of dentin. Although SA promotes an increase in hybrid layer formation, it was not reflected in the μSBS values.