Search

Current American Society of Colorectal Surgery Clinical Practice Guidelines for Ambulatory Anorectal Surgery endorse use of monitored anesthesia care, general anesthesia, or spinal anesthesia based on physician and patient preference. Although several studies support the use of monitored anesthesia care over general anesthesia, the literature regarding spinal anesthesia is limited and heterogenous due to small sample sizes and disparate spinal anesthesia techniques. Saddle block anesthesia is a form of spinal anesthesia that localizes to the lowermost sacral spinal segments allowing for preservation of lower extremity motor function and faster recovery. We accrued one of the largest reported cohort of anorectal procedures using saddle block anesthesia, as such, we sought to evaluate our institutional 12-year experience.Patients who underwent a benign anorectal procedure at our outpatient surgery center between July 2008-2020 were retrospectively reviewed. Demographics, surgical factors, perioperative times, and adverse events were collected from the electronic medical records. Saddle block anesthesia was generally performed in the preoperative area using a spinal needle (25-27 gauge) and a single injection technique of a 1:1 ratio local anesthetic mixed with 10% dextrose solution. Between 2.5-5 mg of hyperbaric anesthetic was injected intrathecally in the sitting position and the patient remained upright for 3-10 minutes. This technique of saddle block anesthesia provides analgesia for approximately 1-3 hours.In the study, 859 saddle block anesthesia patients were identified, with a mean age of 44.6 years and American Society of Anesthesia score of 1.9; 609 (70.9%) were male. Surgical indications included lesion removal (27.1%), anal fistula (25.8%), hemorrhoidectomy (24.7%), pilonidal disease (6.3%), anal fissure (5.8%), and a combination of prior (10.2%). Prone jackknife positioning was used in 91.6% of procedures. Saddle block anesthesia most often was performed with bupivacaine (48.9%) or ropivacaine (41.7%). The median procedural saddle block anesthesia time was 11 minutes, surgery time was 17 minutes, anesthesia time was 42 minutes, and recovery time was 91 minutes. Patients spent a median of 3 hours and 53 minutes in the facility. Adverse events included urinary retention (1.9%), conversion to general anesthesia (1.8%), spinal headache (1.5%), hemodynamic instability (0.9%), and injection site reaction (0.3%).Demonstrated using the largest known cohort of anorectal patients with saddle block anesthesia, saddle block anesthesia provides an effective method of analgesia to avoid general anesthesia with a low rate of adverse events.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3–10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8–11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3–15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Background The Center for Medicare and Medicaid Services decreased reimbursement rates for peripheral venoarterial (VA) extracorporeal membrane oxygenation (ECMO) and venovenous (VV) ECMO procedures in October 2018. Limited data are available describing hospital costs and clinical resources required to support ECMO patients. Methods All patients supported on ECMO at our institution between March 2017 and October 2018 were identified. Exclusion criteria were cannulation at referring hospitals, organ transplant recipients, and temporary right ventricular support. The cohort was stratified by the initial cannulation strategy. Outcomes were total hospital cost and clinical resource utilization. Results There were 29 patients supported on central VA, 72 on peripheral VA, and 37 on VV ECMO. Survival at 30 days was 48% for central vs 37% for peripheral vs 51% for VV. Hospital costs were $187,848 for central vs $178,069 for peripheral vs $172,994 for VV (P = .91). Mean hospital stay was 25.8 days for central vs 21.5 days for peripheral vs 26.2 days for VV (P = .49). Mean intensive care unit stay was 14.1 days for central vs 12.8 days for peripheral vs 7.7 days for VV (P = .25). Mean length of ECMO support was 6.5 days for central vs 6.2 days for peripheral vs 7.8 days for VV (P = .38). Mean ventilator time was 13.0 days for central vs 8.2 days for peripheral vs 10.0 days for VV (P = .06). Hemodialysis was used in 41% central patients, 47% peripheral, and 41% VV (P = .75). Theoretical ECMO reimbursement losses ranged from $1,970,698 to $5,648,219 annually under 2018 Center for Medicare and Medicaid Services rates. Conclusions ECMO cannulation strategy has minimal impact on resource utilization and hospital cost.

Purpose In the MONALEESA-3 Phase III trial of patients with hormone receptor–positive human epidermal growth factor receptor–negative advanced breast cancer, ribociclib plus fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS). Here, we present patient-reported outcomes from the trial, including health-related quality of life (HRQOL). Methods Patients were randomized (2:1) to receive ribociclib plus fulvestrant or placebo plus fulvestrant. Time to definitive 10% deterioration (TTD) from baseline in HRQOL (global health status [GHS] from the EORTC QLQ-C30 questionnaire) and pain (BPI-SF questionnaire) were assessed using Kaplan-Meier estimates; a stratified Cox regression model was used to estimate the hazard ratio (HR) and 95% CIs. Results Deterioration ≥10% in the EORTC-QLQ-C30 GHS was observed in 33% of patients in the ribociclib group vs 34% of patients in the placebo (reference) group (HR for TTD ≥ 10% = 0.81 [95% CI, 0.62–1.1]). Similar findings were noted for TTD ≥5% (HR = 0.79 [95% CI, 0.61–1.0]) and TTD ≥15% (HR = 0.81 [95% CI, 0.60–1.08]). TTD ≥10% in emotional functioning (HR = 0.76 [95% CI, 0.57–1.01]) trended in favor of the ribociclib group, whereas results for fatigue and pain were similar between arms. TTD ≥10% in BPI-SF pain severity index score (HR = 0.77 [95% CI, 0.57–1.05]) and worst pain item score (HR = 0.81 [95% CI, 0.58–1.12]) trended in favor of ribociclib vs placebo. Conclusions In addition to significantly prolonging PFS and OS compared with placebo plus fulvestrant, adding ribociclib to fulvestrant maintains HRQOL., Highlights • Ribociclib + fulvestrant allowed maintenance of global health status (GHS). • Time to deterioration (TTD) by 10% can convey duration until worsening of QOL. • TTD ≥10% was delayed with ribociclib in GHS and emotional functioning. • Ribociclib also demonstrated trends toward delayed TTD vs placebo in pain outcomes.

To study the different characteristics of arterial duct (AD) in a series of prenatally detected right aortic arch (RAA). Out of 832 congenital heart diseases (CHD) referred to a tertiary center, 98 cases had RAA. Based on anatomical landmarks we identified 7 types of AD: type 1 left-sided, transverse; type 2 left-sided, vertical; type 3 from the underside of aortic arch (AA), vertical; type 4 right-sided, mirror-image “V”, transverse; type 5 right-sided, “H” shaped, transverse; type 6 bilateral; type 7 absent or unidentifiable. For each type of AD the incidence of associated major CHD was calculated and chi-square test was applied to verify the null hypothesis with significance level of p

Background The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor–positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−), PIK3CA‐mutated advanced breast cancer (ABC), after cyclin‐dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real‐world setting. Materials and Methods Patients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real‐world patient cohort who received standard‐of‐care from a deidentified clinico‐genomics database (CGDB). Primary and secondary endpoints were to compare progression‐free survival (PFS), estimated by the Kaplan‐Meier method, and the proportion of patients remaining progression‐free at 6 months, respectively, between the two cohorts. Results A total of 855 patients with PIK3CA‐mutant disease who had prior CDK4/6i plus hormone therapy were selected from the CGDB; further matching to 120 patients from BYLieve selected 95 patients without exposure to HER2‐targeting agents, clinical study drug, or alpelisib. In unadjusted and postmatching results, primary and secondary endpoints favored treatment with alpelisib with fulvestrant in BYLieve more than standard treatments in the real‐world cohort. Postadjustment, median PFS for patients treated with alpelisib in BYLieve was 7.3 versus 3.7 months in the real‐world cohort, and 6‐month PFS was 54.6% versus 40.1%, respectively. Conclusion Matched/weighted analysis comparing BYLieve with the real‐world setting further supports the clinical benefit of alpelisib with fulvestrant for treatment of HR+, HER2−, PIK3CA‐mutant ABC after CDK4/6i treatment. Implications for Practice Approximately 40% of patients with hormone receptor–positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−) advanced breast cancer (ABC) have PIK3CA‐mutated tumors, which have been associated with endocrine therapy resistance. Alpelisib, an α‐selective phosphatidylinositol‐3‐kinase inhibitor, demonstrated significantly improved progression‐free survival in SOLAR‐1 and demonstrated clinical efficacy in BYLieve when combined with fulvestrant. Data are limited in comparing the efficacy of alpelisib combined with fulvestrant with effectiveness of standard therapy after CDK4/6i treatment. Using real‐world data, this is the first analysis comparing alpelisib combined with fulvestrant with standard treatments for HR+, HER2−, PIK3CA‐mutant ABC in the post‐CDK4/6i setting., This article reports the efficacy of treatment with alpelisib combined with fulvestrant in a cohort of patients with PIK3CA‐mutated breast cancer compared with the effectiveness of real‐world standard treatments in the post‐CDK4/6i setting using data from a deidentified clinico‐genomics database (CGDB).

Human Papillomavirus (HPV) is known to cause dysplasia and cancer. In cervical disease, there are documented differences in prevalence of HPV genotypes among racial/ethnic groups. Little is known about prevalence of HPV genotypes in anal dysplasia. This study aimed to evaluate association between HPV genotypes and race/ethnicity in a racially heterogenous population with anal dysplasia.This was a single-institution retrospective review of patients treated for anal dysplasia between 2008 and 2019. HPV genotype, obtained via anal swab testing, was recorded as HPV 16, HPV 18, or other non-16/18 high-risk (HR) HPV genotypes. Univariate and multivariate logistic regression analyses were used to evaluate the association between patient factors and HPV genotype.Of 517 patients meeting inclusion criteria, 46.8% identified as White, 37.1% as Black, 13.2% as Hispanic, and 2.9% as other/unknown. Race/ethnicity (P = 0.016) and sex (P 0.001) were significantly associated with differences in prevalence of HPV genotypes. Black (odds ratio 1.56, 95% confidence interval 1.00-2.44) and male (odds ratio 2.35, 95% confidence interval 1.42-3.92) patients were significantly more likely to have non-16/18 HR HPV genotypes.In a racially and socioeconomically diverse cohort of patients with anal dysplasia, Black race and male sex were associated with increased likelihood of infection with a non-16/18 HR HPV genotype. Many of these genotypes are not covered by currently available vaccines. Further study is warranted to evaluate anal HPV genotypes in a larger cohort, as this may have important implications in HPV vaccination and anal dysplasia screening efforts.

Advanced age is associated with comorbidities and immune system impairment, which may influence the efficacy and tolerability of immune checkpoint inhibitors. There is evidence that anti-PD1 antibodies in advanced melanoma are equally effective in patients65 years. However, data on patients75 years are lacking as co-morbidities and logistics often exclude them from clinical trials.We retrospectively reviewed the clinical records of older patients with advanced melanoma undergoing any-line treatment with an anti-PD1 (nivolumab/pembrolizumab) to investigate its clinical effectiveness and toxicity in a real-life setting. Clinical response was assessed using RECIST criteria and toxicity was evaluated according to CTCAE 4.0. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and the Cox model was used to assess potential prognostic factors.174 patients were considered; 59.2% males, median age 79 years (range 75-93). The majority had a performance status of 0 and normal lactate dehydrogenase (LDH) levels (55.2% and 52.4%, respectively). 69.1% had multiple co-morbidities. 56.9% received nivolumab. 36.7% of cases showed an objective response and the disease control rate was 56.3%. Median OS was 17.2 months [95% CI: 8.87-not reached] and a better prognosis was observed for patients with normal LDH (p .001) and lower performance status (p .001). Treatment was well tolerated, only 11 patients experiencing severe (grade 3/4) toxicity. There were no treatment-related deaths. Adverse events were managed with corticosteroids and additional immunosuppressive agents were unnecessary.Anti-PD1 antibodies appear effective and well tolerated in older patients with advanced melanoma.

BACKGROUND Aortic dilatation is common in hypertensive patients and is associated with higher risk of cardiovascular events. Parameters predicting further dilatation during lifetime are poorly understood. AIM To predict the midterm aortic diameter evolution in a cohort of hypertensive patients with known aortic dilatation at Sinus of Valsalva (SOV) level. METHODS We prospectively analyzed a cohort of essential hypertensive outpatients without any other known risk factor for aortic dilatation. They underwent serial echocardiographic evaluations from 2003 to 2016. RESULTS Two hundred and forty-two hypertensive outpatients with a mild-to-moderate (37-53 mm) aortic dilatation were followed up for at least 5 years. Mean growth rate was 0.08 ± 0.35 mm/year. No clinical or anthropometric parameters were significantly different in patients with and without aortic diameter increase. Aortic z score (number of standard deviations from the average value observed in the general population) at baseline was inversely associated with growth rate (R 0.04, P

Background Magnetic resonance imaging (MRI) has become the preferred method for local staging of rectal cancer. Current MRI technology, operating at 1.5-3 T, results in incorrectly reported tumor depth and therefore inaccurate staging in one-third of individuals. Inaccurate staging can result in suboptimal treatment in patients with rectal cancer and can submit them to unnecessary treatments. The Medical College of Wisconsin Center for Imaging Research houses one of approximately twenty experimental 7 T MRIs worldwide capable of imaging the human pelvis. We present our initial experience with this novel imaging technique for the human rectum. Methods This was a prospective observational trial conducted at a single institution. Patients diagnosed with rectal cancer and who underwent low anterior resection or abdominoperineal resection between July 2015 and July 2017 were included. Excised rectal specimens were suspended in a saline-filled container and imaged by MRI at 7T. Tumor depth and lymph node status were determined by a single radiologist who was blinded to the pathologic results. These MRI interpretations were then compared with the pathologic stage. Results Seven of the 10 patients received neoadjuvant chemoradiation. When using the T1-weighted volumetric interpolated breath-hold examination–flex fat-suppressed sequences, radiologic and pathologic interpretation was identical regarding tumor depth in 7 of 10 patients (70%). Nodal status was correctly interpreted by 7T MRI in 8 of 10 patients (80%). Lymph nodes as small as 2 mm were able to be correctly characterized as harboring malignancy. Conclusions We have demonstrated that 7T MRI of the rectum ex vivo has a strong correlation with histologic results. With its superior signal-to-noise ratio and spatial resolution, 7T MRI holds promise in more accurately staging rectal cancer and may be useful in correctly categorizing response to neoadjuvant therapy.

The long-term increase in survival from cutaneous malignant melanoma (CMM) is generally attributed to the decreasing trend in tumour thickness, the single most important prognostic factor.To determine the relative contribution of decreased tumour thickness to the favourable trend in survival from CMM in Italy.Eleven local cancer registries covering a population of 8 056 608 (13.4% of the Italian population in 2010) provided records for people with primary CMM registered between 2003 and 2017. Age-standardized 5-year net survival was calculated. Multivariate analysis of 5-year net survival was undertaken by calculating the relative excess risk (RER) of death. The relative contribution of the decrease in tumour thickness to the RER of death was evaluated using a forward stepwise flexible parametric survival model including the available prognostic factors.Over the study period, tumour thickness was inversely associated with 5-year net survival and multivariate RER in both sexes. The median thickness was 0.90 mm in 2003-2007, 0.85 mm in 2008-2012 and 0.75 mm in 2013-2017 among male patients, and 0.78 mm, 0.77 mm and 0.68 mm among female patients, respectively. The 5-year net survival was 86.8%, 89.2% and 93.2% in male patients, and 91.4%, 92.0% and 93.4% in female patients, respectively. In 2013-2017, male patients exhibited the same survival as female patients despite having thicker lesions. For them, the increasing survival trend was more pronounced with increasing thickness, and the inclusion of thickness in the forward stepwise model made the RER in 2013-2017 vs. 2003-2007 increase from 0.64 [95% confidence interval (CI) 0.51-0.80] to 0.70 (95% CI 0.57-0.86). This indicates that the thickness trend accounted for less than 20% of the survival increase. For female patients, the results were not significant but, with multiple imputation of missing thickness values, the RER rose from 0.74 (95% CI 0.58-0.93) to 0.82 (95% CI 0.66-1.02) in 2013-2017.For male patients in particular, decrease in tumour thickness accounted for a small part of the improvement in survival observed in 2013-2017. The introduction of targeted therapies and immune checkpoint inhibitors in 2013 is most likely to account for the remaining improvement.

Background Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC. Methods Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies. Results The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I2 = 35%) and shorter median OS (-8.4 [-13.4, -3.5], I2 = 58%, N = 1,545). Findings were similar for PFS rates at 6 months (odds ratio [95% CI]: 0.74 [0.59, 0.94], I2 = 42%, N = 3,160) and 12 months (0.76 [0.59, 0.99], I2 = 42%, N = 2,468) and directionally consistent but not statistically significant at 18 months (N = 1,726). Conclusions Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.

High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed. We designed a phase II, single-arm clinical trial for patients with MM and RCC. The treatment schedule consisted of 3 daily doses of 6-12 Gy of RT to 1-5 non-index metastatic fields, before IL-2 at the first and third treatment cycle. HD IL-2 was administered by continuous infusion for 72 hours and repeated every 3 weeks for up to 4 cycles, thereafter every 4 weeks for a maximum of 2 cycles. The primary endpoint was the immunological efficacy of the combined RT/HD IL-2 treatment (assessed by IFN-γ ELISPOT). Nineteen out of 22 patients were evaluable for immunological and clinical response. Partial response occurred in 3 (15.7%) patients and stable disease was observed in 7 (36.8%). The disease control rate was 52.6% after a median follow up of 39.2 months. According to Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0), the majority of toxicities were grade 1-2. Immunological responses were frequent and detected in 16 (84.2%) patients. Increased levels of IL-8 and IL-10 in melanoma, circulating effector memory CD4+ and intratumoral CD8+ T cells in both tumor types were detected after therapy. Overall the treatment was well tolerated and immunologically active. Immunomonitoring and correlative data on tumor and peripheral blood cell subsets suggest that this combination treatment could be a promising strategy for patients progressing after standard treatments.

Dendritic cell (DC)-based vaccination effectively induces anti-tumor immunity, although in the majority of cases this does not translate into a durable clinical response. However, DC vaccination is characterized by a robust safety profile, making this treatment a potential candidate for effective combination cancer immunotherapy. To explore this possibility, understanding changes occurring in the tumor microenvironment (TME) upon DC vaccination is required. In this line, quantitative and qualitative changes in tumor-infiltrating T lymphocytes (TILs) induced by vaccination with autologous tumor lysate/homogenate loaded DCs were investigated in a series of 16 patients with metastatic melanoma. Immunohistochemistry for CD4, CD8, Foxp3, Granzyme B (GZMB), PDL1, and HLA class I was performed in tumor biopsies collected before and after DC vaccination. The density of each marker was quantified by automated digital pathology analysis on whole slide images. Co-expression of markers defining functional phenotypes, i.e., Foxp3+ regulatory CD4+ T cells (Treg) and GZMB+ cytotoxic CD8+ T cells, was assessed with sequential immunohistochemistry. A significant increase of CD8+ TILs was found in post-vaccine biopsies of patients who were not previously treated with immune-modulating cytokines or Ipilimumab. Interestingly, along with a maintained tumoral HLA class I expression, after DC vaccination we observed a significant increase of PDL1+ tumor cells, which significantly correlated with intratumoral CD8+ T cell density. This observation might explain the lack of a significant concurrent cytotoxic reactivation of CD8+ T cell, as measured by the numbers of GZMB+ T cells. Altogether these findings indicate that DC vaccination exerts an important role in sustaining or de novo inducing a T cell inflamed TME. However, the strength of the intratumoral T cell activation detected in post-DC therapy lesions is lessened by an occurring phenomenon of adaptive immune resistance, yet the concomitant PDL1 up-regulation. Overall, this study sheds light on DC immunotherapy-induced TME changes, lending the rationale for the design of smarter immune-combination therapies.

The proportion of new diagnoses of HIV infection in immigrants residing in Italy raised from 11% in 1992 to 29.7% in 2018. To investigate the HIV clades circulating in this community a retrospective study was performed in 557 HIV-infected immigrants living in 12 Italian cities. Immigrants originated from East-Europe and Central-Asia (11.7%), North Africa and Middle East (7.3%), South and South-East Asia (7.2%), Latin America and the Caribbean (14.4%), and sub-Saharan Africa (59.4%). More than 87% of immigrants were on antiretroviral therapy (ART), although 26.6% of them were viremic. A 22.0% of immigrants had hepatitis (HBV and/or HCV) and/or tuberculosis. HIV phylogenetic analysis on sequences from 192 immigrants showed the presence of clades B (23.4%), G (16.1%), C (10.4%), A1 (9.4%), F1 (5.2%), D (1.6%) and Circulating Recombinant Forms (CRFs) (33.9%). CRF02_AG represented 72.3% of the total CRFs. Clusters between immigrants and Italian natives were also present. Drug resistance mutations to NRTI, NNRTI, and PI drug classes occurred in 29.1% of ART-treated and in 12.9% of ART-naïve individuals. These data highlight the need for tailored public health interventions in immigrants to avoid spreading in Italy of HIV genetic forms and ART-resistant variants, as well as HIV co-morbidities.

Hypohydration has been suggested increasing the risk of vascular diseases, and it is associated with poor prognosis and worse functional outcome in stroke. Most studies have used blood parameters to determine patients’ hydration status. The aim of this study was to measure urine osmolality (uOsm) and its influence on stroke severity and independence. A prospective descriptive study was conducted in stroke patients admitted to a stroke unit. All patients underwent neurological evaluation at admission and discharge using the National Institute of Health Stroke Scale (NIHSS). Independence at discharge was evaluated with the Barthel Index (BI) and the modified Rankin Scale (mRS). uOsm was measured at admission. Patients were grouped in “poor fluid intake” (PF) and “euhydration” (EU), the latter if uOsm ≤ 500 mOsm/kg. Among 119 included patients, the prevalence of PF was 52%, with no difference observed between groups in demographics or blood samples analyses. PF had higher chances of NIHSS > 8 at admission (OR: 4.7 95% CI: 1.3–17.0; p = 0.02), lower BI at discharge (β: −15.3 95% CI: −26.7 to −3.8; p = 0.01), and worse mRS at discharge (OR: 4.01 95% CI: 1.2–14.0; p = 0.02). These findings are consistent with previous results, suggesting that uOsm may be a factor significantly associated with stroke severity and independence outcome after acute ischemic stroke.

Introduction: Recombinant tissue plasminogen activator (rt-PA) is the first-line therapy demonstrated to be safe and effective in acute ischemic stroke. People with pre-existing severe dementia or physical disability are usually excluded from rt-PA. The aim of our study was to investigate rt-PA safety and effectiveness in acute stroke with pre-existing disability (mRS ≥ 2). Methods: The study encompassed 35 acute ischemic stroke patients with mRS ≥ 2 treated with rt-PA. In order to assess the differences in clinical outcome in three disability groups (mRS = 2; 3; 4/5), the following parameters were evaluated: intracerebral hemorrhage, mortality, NIHSS, ΔNIHSS and mRS. Results: Baseline-NIHSS and age were not significantly different among groups. Mortality was higher in the pre-morbid mRS 4/5 group (44%) than in the pre-morbid mRS 2 (16.7%) and mRS 3 groups (21.4%). In survived patients, median ΔNIHSS% was higher in the mRS 2 and 3 groups (-63.3% and −92.3%, respectively) than in the mRS 4/5 group (−9.1%). The 247 rt-PA treated subjects with mRS < 2 in the same period showed lower mortality rate (4.7%), lower sICH (5%), lower mRS at discharge (median 1; range 0–6) and similar ΔNIHSS% (−75%). Conclusion: Patients with mRS 2 and 3 may benefit from rt-PA with a moderate risk of sICH and mortality.

Backgrounds: Wake-Up Stroke (WUS) patients are generally excluded from thrombolytic therapy (rTPA) due to the unknown time of stroke onset. This study aimed to investigate the effects of rTPA in WUS patients during every day clinical scenarios, by measuring ischemic lesion volume and functional outcomes compared to non-treated WUS patients. Methods: We retrospectively analyzed clinical and imaging data of 149 (75 rTPA; 74 non-rTPA) patients with acute ischemic WUS. Ischemic volume was calculated on follow-up CT and functional outcomes were the NIHSS and mRS comparing rTPA and non-rTPA WUS. Patients were selected using ASPECTS > 6 on CT and/or ischemic penumbra > 50% of hypoperfused tissue on CTP. Results: A reduced volume was measured on the follow-up CT for rTPA (1 mL, 0-8) compared to the non-rTPA patients (10 mL, 0-40; p = 0.000). NIHSS at 7 days from admission was significantly lower in the rTPA (1, 0-4) compared to non-rTPA group (3, 1-9; p = 0.015), as was the percentage of improvement (ΔNIHSS) (70% vs 50%; p = 0.002). A higher prevalence of mRS 0-2 was observed in the rTPA compared to the non-rTPA (54% vs 39%; p = 0.060). Multivariate analysis showed that NIHSS at baseline and rTPA treatment are significant predictors of good outcome both in terms of NIHSS at 7 days and ischemic lesion volume on follow-up CT (p < 0.05). Conclusions: rTPA in WUS patients selected with CT and/or CTP resulted in reduced ischemic infarct volume on follow-up CT and better functional outcome without increment of intracranial hemorrhages and in-hospital mortality.

Background Patients with coronavirus disease 2019 (Covid-19) may experience venous thrombosis while data regarding arterial thrombosis are sparse. Methods Prospective multicenter study in 5 hospitals including 373 patients with Covid-19-related pneumonia. Demographic data, laboratory findings including coagulation tests and comorbidities were reported. During the follow-up any arterial or venous thrombotic events and death were registered. Results Among 373 patients, 75 (20%) had a thrombotic event and 75 (20%) died. Thrombotic events included 41 venous thromboembolism and 34 arterial thrombosis. Age, cardiovascular disease, intensive care unit treatment, white blood cells, D-dimer, albumin and troponin blood levels were associated with thrombotic events. In a multivariable regression logistic model, intensive care unit treatment (Odds Ratio [OR]: 6.0; 95% Confidence Interval [CI] 2.8–12.6; p p = 0.022); and albumin levels (OR: 0.49; 95% CI 0.28–0.87; p = 0.014) were associated with ischemic events. Age, sex, chronic obstructive pulmonary disease, diabetes, heart failure, coronary heart disease, intensive care unit treatment, in-hospital thrombotic events, D-dimer, C-reactive protein, troponin, and albumin levels were associated with mortality. A multivariable Cox regression analysis showed that in-hospital thrombotic events (hazard ratio [HR]: 2.72; 95% CI 1.59–4.65; p p = 0.001), and albumin (HR: 0.447; 95% CI 0.277–0.723; p = 0.001) predicted morality. Conclusions Covid-19 patients experience an equipollent rate of venous and arterial thrombotic events, that are associated with poor survival. Early identification and appropriate treatment of Covid-19 patients at risk of thrombosis may improve prognosis.

Current treatment for locally advanced rectal cancer includes neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. With neoadjuvant chemotherapy (NC), both chemoradiation and chemotherapy are given in the neoadjuvant setting. This study aims to assess patterns of NC utilization and differences in treatment response compared with standard treatment at our institution.We performed a retrospective review of patients treated for stage II-III rectal cancer at our institution between 2008 and 2018, examining patient demographics, tumor characteristics, and treatment modality. The primary outcome of interest was complete response (CR) to treatment, including both pathologic and clinical CR.Of 184 patients, 134 (72.8%) received standard therapy, and 50 (27.2%) received NC. In the standard treatment group, 70.1% were node positive, and 9.0% had T4-disease, compared with 92.0% and 26.0% in the NC group, respectively (both P 0.01). NC utilization increased over time, with 3.4% of patients receiving NC between 2008 and 2012, compared with 48.5% in 2013-2018 (P 0.01). CR was achieved in 19.4% versus 34.0% (P 0.01) of patients in standard versus NC groups. With multivariate analysis, NC (odds ratio = 3.02 [95% confidence interval 1.37-6.67], P = 0.01) was associated with increased likelihood of achieving CR, whereas higher T-stage was associated with decreased likelihood of CR (for cT4, odds ratio = 0.06 [95% confidence interval 0.01-0.56], P = 0.01).Use of NC was increasingly used at our institution from 2008 to 2018. Patients who received NC achieved higher rates of CR compared with those undergoing standard therapy, despite having more advanced disease. These data support trends from other institutions and provides rationale for further study regarding use of NC for locally advanced rectal cancer.

Trans-duodenal ampullectomy (TDA) is a surgical option for the treatment of selected ampullary neoplasms. The aim of this study was to evaluate our experience with TDA for the treatment of ampullary neoplasms, focusing on indications, technical aspects, and short- and long-term outcomes. All TDAs for ampullary neoplasms performed between January 2010 and December 2018 at our institution were retrospectively evaluated. Patients had ampullary neoplasms with low-grade dysplasia or in situ carcinoma (Tis) not suitable for an endoscopic approach, ampullary carcinoma unfit for pancreaticoduodenectomy (PD), or ampullary neuroendocrine G1-tumours. Thirty-six patients were included in the study: 9 (25.0%) with neoplasms with low-grade dysplasia, 4 (11.1%) with G1 neuroendocrine tumours and 23 (63.9%) with Tis or invasive carcinoma. Mean operative time was 252.5 min. Overall and severe (Clavien–Dindo > IIIa) morbidity rate was 44.4% and 13.9%, respectively. No 90-day mortality was observed. At follow-up, no deaths were observed and local recurrence rate was 11.1% for patients with ampullary adenomas with low-grade dysplasia. Among four patients with neuroendocrine neoplasms, only one developed recurrence (pulmonary). Tis, T1 and T2 lesions were found in 16 (69.6%), 2 (8.7%) and 5 (21.7%) patients, respectively: recurrence occurred in 3 patients with Tis lesions (one malignant), no patients with T1 neoplasms and 2 patients with T2 lesions (3 patients had a survival of > 3 years). TDA is a feasible and effective surgical procedure for the treatment of ampullary adenomas with low-grade dysplasia when endoscopic approach is contraindicated or has failed. For lesions with evidence of malignancy, TDA seems to be an oncological safe procedure for Tis ampullary cancer and a good palliative procedure for patients unfit for PD. Moreover, TDA may be appropriate for the treatment of G1 ampullary neuroendocrine neoplasms. A large multicentre study of TDA for early ampullary cancers is needed.

Left hemicolectomy and complicated sigmoid colectomy require an anastomosis between the transverse colon and rectum. Generous mobilization will typically allow the colon to reach to the rectum. However, despite full mobilization of the splenic flexure and extensive work on the mesentery, there are cases in which reach to the pelvis is still an issue. Retroileal routing of the colon is one technique for overcoming such a reach problem and achieving a tension-free anastomosis. Performing retroileal routing using laparoscopic techniques has been reported rarely, and to date, there are no data on this technique when performed in a hand-assisted laparoscopic fashion. This study aimed to describe the feasibility of doing a retroileal routing using a hand-assisted laparoscopic technique. This was a retrospective chart review of patients who underwent a colon or rectal resection, either open or laparoscopic, with a pelvic anastomosis, by a single colorectal surgeon at an academic institution between 2008 and 2015 with a focus on the immediate and long-term postoperative complications, estimated blood loss, and operating room time for patients having an operation that included retroileal routing for construction of a colorectal anastomosis. A total of 340 patients fit inclusion criteria and of these, 13 underwent hand-assisted laparoscopic procedures with retroileal routing of the proximal colon to the colorectal anastomosis. Postoperative morbidity included intubation for CO2 retention in one patient and a RLL effusion in another patient; there were no anastomotic leaks. Long-term morbidities included two ventral hernias at 2 years postoperatively. Mean operating room time was 208 min. There were no 30- or 90-day mortalities. Hand-assisted laparoscopic retroileal routing is a feasible and safe technique in accomplishing a tension-free colorectal anastomosis when proximal colon length makes standard routing of the colon to the rectum an issue.

Organ allocation for transplantation aims to balance the principles of justice and medical utility to optimally utilize a scarce resource. To address practical considerations, the United States is divided into 58 donor service areas (DSA), each constituting the first unit of allocation. In November 2017, in response to a lawsuit in New York, an emergency action change to lung allocation policy replaced the DSA level of allocation for donor lungs with a 250 nautical mile circle around the donor hospital. Similar policy changes are being implemented for other organs including heart and liver. Findings from a recent US Department of Health and Human Services report, supplemented with data from our institution, suggest that the emergency policy has not resulted in a change in the type of patients undergoing lung transplantation (LT) or early postoperative outcomes. However, there has been a significant decline in local LT, where donor and recipient are in the same DSA. With procurement teams having to travel greater distances, organ ischemic time has increased and median organ cost has more than doubled. We propose potential solutions for consideration at this critical juncture in the field of transplantation. Policymakers should choose equitable and sustainable access for this lifesaving discipline.

Background: One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour. Objectives: The aim of the study was to evaluate the role of endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center. Methods: A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading. Results: The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%. Conclusion: EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.

We aimed to evaluate the performance of a mathematical model and currently available non-invasive techniques (generalized transfer function (GTF) method and brachial pressure) in the estimation of aortic pressure. We also aimed to investigate error dependence on brachial pressure errors, aorta-to-brachial pressure changes and demographic/clinical conditions. Sixty-two patients referred for invasive hemodynamic evaluation were consecutively recruited. Simultaneously, the registration of the aortic pressure using a fluid-filled catheter, brachial pressure and radial tonometric waveform was recorded. Accordingly, the GTF device and mathematical model were set. Radial invasive pressure was recorded soon after aortic measurement. The average invasive aortic pressure was 141.3 ± 20.2/76 ± 12.2 mm Hg. The simultaneous brachial pressure was 144 ± 17.8/81.5 ± 11.7 mm Hg. The GTF-based and model-based aortic pressure estimates were 133.1 ± 17.3/82.4 ± 12 and 137 ± 21.6/72.2 ± 16.7 mm Hg, respectively. The Bland-Altman plots showed a marked tendency to pressure overestimation for increasing absolute values, with the exclusion of mathematical model diastolic estimations. The systolic pressure was increased from the aortic to radial locations (7.5 ± 19 mm Hg), while the diastolic pressure was decreased (3.8 ± 9.8 mm Hg). The brachial pressure underestimated the systolic and overestimated diastolic intra-arterial radial pressure. GTF errors were independently correlated with the variability in pulse pressure amplification and with the brachial error. Errors of the mathematical model were related to only demographic and clinical conditions. Neither a multiscale mathematical model nor a generalized transfer function device substantially outperformed the oscillometric brachial pressure in the estimation of aortic pressure. Mathematical modeling should be improved by including further patient-specific conditions, while the variability in pulse pressure amplification may hamper the performance of the GTF method in patients at the risk of coronary artery disease.

Background Human papillomavirus is a common sexually transmitted infection that may affect the oropharynx, genitalia, or anus. Some strains of this virus may cause bulky growths around the anus known as giant anal condylomas. These can become large, disfiguring, and may cause bleeding, as well as difficulty with defecation and hygiene. Surgical management is usually necessary for large condylomas, whereas office-based procedures are common for smaller lesions. It is unclear why some develop large anal margin tumors, whereas others develop limited disease. The aim of the present study was to evaluate for risk factors that may play a role in the development of extensive disease warranting operative management. Materials and methods A retrospective chart review of patients seen within the Anal Dysplasia Clinic at the Medical College of Wisconsin was undertaken. Clinic encounters for patients with anogenital condyloma were abstracted for demographic information, operative interventions, Human Immunodeficiency Virus status, and smoking history to determine risk factors that predicted operative intervention for giant anal condylomas. Results A total of 239 patients met inclusion criteria; 211 (88.3%) were male and 28 (11.7%) were female. Racial makeup of the cohort included 49% Caucasian, 38.9% African-American, 9.2% Hispanic, and 2.9% were identified as another ethnicity. One hundred forty-three patients (60.1%) were current or past smokers. One hundred ninety-eight (82.8%) patients tested positive for human immunodeficiency virus (HIV), whereas 41 (17.2%) were negative. Multiple linear regression identified only African-American race as predictive of greater disease burden. Conclusions African-American race was associated with increased size of anal condyloma. As the size of anal condylomas increase, management shifts from topical treatments to operative intervention. This is the first study to correlate race with burden of disease in the general population.

In the phase III SOLAR-1 trial (NCT02437318), the PI3Kα-selective inhibitor and degrader alpelisib significantly improved median progression-free survival when added to fulvestrant in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (In theGlobal Health Status/QoL and functional status were maintained from baseline (mean changes10 points) in the alpelisib (overall change from baseline [95% CI], -3.50 [-8.02 to 1.02]) and placebo arms (overall change from baseline [95% CI], 0.27 [-4.48 to 5.02]). Overall treatment effect in Global Health Status/QoL was not significantly different between arms (-3.77; 95% CI, -8.35 to 0.80;In SOLAR-1, there was no statistical difference in deterioration of Global Health Status/QoL between arms, whereas symptom subscales favored placebo for diarrhea, appetite loss, nausea or vomiting, and fatigue, known side effects of alpelisib. Treatment decisions must consider efficacy and tolerability; taken with clinical efficacy, these results support the benefit-risk profile of alpelisib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative

Aims Atrial fibrillation (AFib) is associated with cognitive decline/dementia, independently from clinical strokes or transient ischaemic attacks (TIA). Recent in silico data suggested that AFib may induce transient critical haemodynamic events in the cerebral microcirculation. The aim of this study is to use non-invasive spatially resolved cerebral near-infrared spectroscopy (SRS-NIRS) to investigate in vivo beat-to-beat microcirculatory perfusion during AFib and after sinus rhythm (SR) restoration. Methods and results Cerebral SRS-NIRS with high-frequency sampling (20 Hz) and non-invasive systemic haemodynamic monitoring were recorded before and after elective electrical cardioversion (ECV) for AFib or atrial flutter (AFL). To assess beat-to-beat effects of the rhythm status, the frequency distribution of inter-beat differences in tissue haemoglobin index (THI), a proxy of microcirculatory cerebral perfusion, was compared before and after SR restoration. Fifty-three AFib/AFL patients (mean age 69 ± 8 years, 79% males) were ultimately enrolled. Cardioversion was successful in restoring SR in 51 (96%) patients. In front of a non-significant decrease in arterial blood pressure extreme events between pre- and post-ECV measurements, a significant decrease of both hypoperfusive and hyperperfusive/hypertensive microcirculatory events was observed after SR restoration (P Conclusion The present is the first in vivo demonstration that SR restoration by ECV significantly reduces the burden of extreme single-beat haemodynamic events in cerebral microcirculation. Future studies are needed to assess whether SR maintenance might slow long-term AFib-correlated cognitive decline/dementia.

Background This pooled analysis of MONALEESA trials evaluated the safety of ribociclib plus endocrine therapy (RIB + ET) with a focus on dose reductions in first-line patients. Methods In the dose reduction analysis, data were pooled from MONALEESA-2 (all patients), MONALEESA-3 (patients receiving treatment as first-line ET) and MONALEESA-7 (patients receiving combination therapy with an NSAI as initial ET). Efficacy was analysed by ribociclib relative dose intensity (DI). Safety was analysed in all patients in the trials (except those receiving tamoxifen in MONALEESA-7) and those with/without ≥1 ribociclib dose reduction. Results Of 818 women who received first-line RIB + ET, 41.8% required ≥1 dose reduction due to AEs (most commonly, neutropenia). Median RIB relative DI in patients without and with dose reductions was 99.3% and 65.6% in MONALEESA-2, 98.4% and 67.8% in MONALEESA-3 and 98·0% and 66·3% in MONALEESA-7. Median PFS was 24.8, 24.9 and 29.6 months for patients who received ≤71% (30th percentile), 72-96% (60th percentile) and 97-100% (90th percentile) RIB relative DI, respectively. No new safety signals emerged in the pooled safety analysis. Conclusions This analysis provides reassuring data showing that the clinical benefit of RIB is preserved when dose modifications are undertaken to manage AEs. Trial registration MONALEESA-2 (NCT01958021) first posted October 8, 2013; MONALEESA-3 (NCT02422615) first posted April 21, 2015; MONALEESA-7 (NCT02278120) first posted October 29, 2014.

In the field of adolescent gambling prevention, there is a lack of intervention studies reporting and assessing training courses for the intervention providers. The present work fills this gap by realizing a dissemination study inside the PRIZE program aimed at modifying a set of cognitive protective factors and affective risk factors. The purpose of this work was twofold: To develop and evaluate a training course with the intervention providers (Study 1), and to assess the short- and long-term effects of the intervention itself (Study 2). The training course was delivered to 44 health professionals (32 females, Mage = 39.34 years). Results showed a significant increase of correct knowledge about gambling and a significant reduction of their susceptibility to probabilistic reasoning biases. Participants also actually learnt the main competencies to conduct the educational activities, they were satisfied for the training course received, and they felt high levels of self-efficacy. The intervention was implemented with 1894 high school students (61% males; Mage = 15.68 years). In the short term, we found a significant increase of adolescents’ correct gambling knowledge, random events knowledge, and probabilistic reasoning ability, and a significant decrease of superstitious thinking, monetary positive outcome expectation, and gambling-related erroneous thoughts and fallacious behavioral choices. In the long-term, a significant decrease of gambling frequency, gambling versatility, and gambling problem severity was obtained. Overall, this work highlights the importance to train prevention program providers in order to optimize the effectiveness of large-scale gambling intervention programs towards adolescents.

Although immunomodulating antibodies are highly effective in metastatic melanoma, their toxicity, related to the activation of T lymphocytes, can be severe. Anticancer vaccines promote a fairly specific response and are very well tolerated, but their effectiveness has yet to be demonstrated. We have been treating patients with advanced melanoma with an autologous dendritic cell vaccine since 2001; to better characterize the safety and efficacy of our product, we designed a retrospective study on all of our patients treated with the vaccine to date. We retrospectively reviewed both case report forms of patients included in clinical trials and medical records of those treated within a compassionate use program. Response was assessed according to the Response Evaluation Criteria In Solid Tumors criteria and toxicity has been graded according to CTCAE 4.0. Although the response rate has been rather low, the median overall survival of 11.4 months and the 1-year survival rate of 46.9% are encouraging, especially considering the fact that data were obtained in a heavily pretreated population and only about one quarter of the patients had received ipilimumab and/or BRAF inhibitors. Multivariate analysis confirmed that the development of an immune response was significantly correlated with a better prognosis (hazard ratio 0.54; P=0.019). The adverse events observed were generally mild and self-limiting. Our analysis confirms the excellent tolerability of our vaccine, making it a potential candidate for combination therapies. As efficacy seems largely restricted to immunoresponsive patients, future strategies should aim to increase the number of these patients.

Objective A very high-resolution (70 MHz) ultrasound device (VHRUS) has recently been approved for use in humans. The aim of this study was to use VHRUS to collect data on healthy subjects to propose some reference values for the digital branches of the median nerves of the hand. Methods A VHRUS with 70 MHz linear array transducer was used to measure the cross sectional area of the median nerve at the wrist (CSAw) and digital branches (CSAf), largest and smallest fascicles, the fascicles number (Nfasc), the fascicle density (FD), the flattening ratio (FR) and CSAw/CSAf. Results Data from 20 healthy subjects were obtained for both hands. The median nerve at the wrist and digital branches were properly identified without anatomical alterations. No differences were found between the right and the left hand. In the dominant hand, CSAw was 9.35 mm2 (4.57–12.35) and Nfasc was 24 (18–38). FD and FR were respectively 2.94 (2.47–4.91) and 2.74 (1.70–4.90). Conclusion VHRUS technology can visualize the median nerves at the wrist, their internal structure and their small branches at the fingers, providing both a qualitative and quantitative assessment. Results from this study provide preliminary reference values in a young healthy sample. Significance Most conventional ultrasound devices are not able to properly visualize the distal branches of the median nerve. In contrast, VHRUS allows to detect and measure smaller structures of the nerve, assisting in clinical practice.

Objectives The combined use of perfusion neuroimaging and brain oscillatory activity may provide a better clinical picture of neurovascular coupling of the injured area in ischemic stroke. The aim is to assess stroke-related topographic electroencephalography (EEG) changes during the earliest phase of ischemic stroke and to compare them with hypoperfusion identified by computer tomography perfusion (CTP). Patients and methods The study included 15 patients with ischemic stroke, who underwent both CTP and EEG recording within 4.5 h. Topographic representation of power for each band was calculated and compared with hypoperfusion areas estimated by CTP maps. Results Predominance of slow delta frequencies was found in all patients. The main finding is the agreement between slow rhythms hemispheric prevalence on EEG maps and cerebral hypoperfusion area identified using CTP. Conclusion The results of this preliminary study show that the combined use of EEG and CTP, as highly available techniques, in acute ischemic stroke may be helpful in clinical practice and provide information about functional and metabolic aspects of brain involvement. The joint use of these methodologies may give a better clinical insight of the functionality of injured area in the hyperacute phase.

Background Neurovascular Coupling is the cerebral mechanism responsible for linking neuronal activity, cerebral metabolism and regional cerebral blood flow (CBF). The direct relation between functional brain activity during active, passive and motor imagery paradigms and changes in CBF has been widely investigated using different techniques. However, CBF changes have not been investigated beat by beat during robot assisted passive movement (PM) and motor imagery (MI) of lower limb, yet. Materials and methods We investigated beat-to-beat hemodynamic changes in 8 healthy subjects using TCD during MI and robot-assisted PM of lower limb. Results The results showed that MI and PM induce a significant CBFv increase and that PM and MI lead to similar hemodynamic changes in healthy subjects. Conclusions The findings may be useful to better understand the variation of CBFv in brain pathology and to develop more specific and efficient rehabilitation therapy protocols in neurological diseases, such as stroke.

Introduction Thrombolysis may affect ischemic stroke-related size, pattern and nature of infarcts, and has the potential to change aphasia presentation and recovery. Data on evolution of post-stroke aphasia following thrombolysis are still scarce. The aim of this study was to determine the course of language recovery through a well-validated language assessment battery after acute ischemic stroke and investigate whether traditional categorical classifications of aphasia can describe the clinical picture in post-thrombolysis phase. Materials and methods Demographic, clinical, and language assessment data of 116 patients presenting sub-acute ischemic stroke aphasia (41 treated with r-tPA; 75 non-treated) were retrospectively analyzed. The participants were assessed by a clinical neuropsychologist with a variety of subtests taken from a well-validated Italian language battery (Neuro-Psychological Aphasia Evaluation). Results The percentage of resolved aphasia was significantly higher in treated patients compared to non-treated patients (p = 0.005) and global aphasia was more common in the non-treated group (non-treated 30.7% vs treated 17.1%). Aphasia subtypes and stroke etiologies showed no significant association, except for small vessel etiology and resolved aphasia (p = 0.041). Reperfusion treatment, baseline NIHSS, and lacunar stroke were the predictors of aphasia recovery. Conclusion The percentage of resolved aphasia was significantly higher in the treated patients compared to the non-treated, with the latter showing a higher percentage of global aphasia. Identifying classic aphasia subtypes after thrombolysis is still possible since reperfused areas do not necessary change the classification or lead to completely different aphasic syndromes. Reperfusion treatment, baseline NIHSS, and lacunar stroke were the main predictors of aphasia recovery.

Introduction Stroke mimics (SM) account for 1% to 41% of all AIS presentation. Seizures are the most frequent cause of mimic, but isolated speech impairment, among adult-onset epilepsy, is quite rare, while aphasia is more often due to an AIS. Prompt AIS/SM recognition is required to establish the most appropriate therapeutic management. We aimed at identifying some predictive clinical and anamnestic features useful to differentiate SM from AIS, particularly in patients presenting with aphasia. Materials and methods A retrospective study of patients admitted for a suspected stroke, from January 2015 until January 2017 was performed. We identified patients discharged with a final diagnosis of aphasia and patients with seizures presenting with speech impairment. Anamnestic, clinical and diagnostic were reviewed. Univariate analyses determined key clinical features predictive of AIS versus an epileptic SM. Results 72 patients with sudden onset of aphasia were identified. A cerebrovascular etiology was diagnosed in 50 patients while an epileptic SM in 22. The presence of ischemic cardiopathy, atrial fibrillation and mild lateralizing signs were strongly suggestive of stroke. Otherwise, a previous history of epilepsy, alteration of consciousness, concomitant infection and electrolyte imbalance were predictors of a SM. Conclusions Our study underscores the importance of an accurate clinical bed-side assessment as the first step in the diagnostic and therapeutic decision-making process for patients presenting with aphasia. The detection of clinical and anamnestic features associated with an epileptic SM could be useful for the diagnostic process and for time-critical treatments.

Background Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. Methods We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. Results Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes (Adjusted Odds Ratio (adjOR) 2.04, 95%CI 1.12–3.73, p = 0.020), hypertension (adjOR 2.31, 95%CI: 1.37–3.92, p = 0.002) and COPD (adjOR 2.67, 95%CI 1.23–5.80, p = 0.013). Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions (adjOR 3.19 95%CI 1.61–6.34, p = 0.001). The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors (adjOR 1.66, 0.90–3.06, adjp = 0.10). Conclusions Patients with diabetes hospitalized for Covid-19 present with high-risk features. They are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions.

AIMS To build a tool to assess the management of inpatients with diabetes mellitus and to investigate its relationship, if any, with clinical outcomes. MATERIALS AND METHODS A total of 678 patients from different settings, Internal Medicine (IMU, n = 255), General Surgery (GSU, n = 230) and Intensive Care (ICU, n = 193) Units, were enrolled. A work-flow of clinical care of diabetes was created according to guidelines. The workflow was divided into five different domains: (a) initial assessment; (b) glucose monitoring; (c) medical therapy; (d) consultancies; (e) discharge. Each domain was assessed by a performance score (PS), computed as the sum of the scores achieved in a set of indicators of clinical appropriateness, management and patient empowerment. Appropriate glucose goals were included as intermediate phenotypes. Clinical outcomes included: hypoglycaemia, survival rate and clinical conditions at discharge. RESULTS The total PS and those of initial assessment and glucose monitoring were significantly lower in GSU with respect to IMU and ICU (P

Psychotherapy is the cornerstone of treatment for borderline personality disorder (BPD) while pharmacotherapy should be considered only as an adjunctive intervention. In clinical practice, however, most of BPD patients only receive medication. The aim of the study is to first describe pharmacological treatment in BPD patients in Italy and secondly to evaluate if comorbidity or illness severity are associated with the prescription of different class compounds. Data on pharmacological treatment and clinical evaluation of 75 BPD patients were collected in 5 clinical settings. The association between comorbidity and medication was assessed. Moreover, we evaluated the association between pharmacotherapy and severity, defined by a cluster analysis aimed at detecting different groups of patients. Most of the participants (82.7%) were characterized by polypharmacy, with a mean of 2.4 medications per person. Interestingly, the prescription didn't seem to depend on/be based on the severity of the disorder and was only partially determined by the presence of comorbidity. In conclusion, our findings are similar to what described in other clinical studies, supporting the idea that medication management for BPD is only partially coherent with international guidelines. This pilot study confirms the need for more rigorous studies to gain greater understanding of this topic and diminish the gap between guidelines and the real clinical world.

BackgroundPlanning in behavioral weight loss (BWL) programs helps participants enact changes in eating and exercise, although the direct impact on weight loss is unclear.PurposeTo examine how meal and exercise planning frequencies change in a BWL program and their relations to weight loss outcomes.MethodsParticipants (N = 139) in a 40 week worksite-based BWL program completed a questionnaire regarding meal and exercise planning frequency at Weeks 0, 10, 20, 30, and 40 and were weighed weekly. Growth curve models were used to determine trajectories in meal and exercise planning frequency and to assess the role of an individual’s average meal and exercise planning (between-person effect) and individual variation in planning (within-person effect) on body mass index (BMI).ResultsThe best-fitting model, a linear random effect with a quadratic fixed-effect model, demonstrated that meal and exercise planning frequency increased over the course of the program with slowing growth rates. Between participants, higher average meal planning frequency (B = −0.029, t = −3.60), but not exercise planning frequency, was associated with greater weight loss. Within participants, exercise planning, but not meal planning, predicted a higher than expected BMI (B = 3.17, t = 4.21).ConclusionsFrequent meal planning should be emphasized as a continued, as opposed to intermittent, goal in BWL programs to enhance weight loss. Average exercise planning frequency does not impact weight loss in BWL programs; however, acute increases in exercise planning frequency may be a popular coping strategy during a weight loss setback or, alternatively, may lead to increased calorie consumption and weight gain.

The robotic platform is increasingly used in colorectal surgery. Recent upgrades in the robotic platform and introduction of proctectomy-specific reports from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) warrant updated evaluation of minimally invasive proctectomy outcomes. The aim of this study was to compare outcomes in robotic versus laparoscopic proctectomy using ACS-NSQIP data.The ACS-NSQIP data set was used to identify adult patients undergoing elective robotic and laparoscopic proctectomy in 2016 and 2017. Demographics, preoperative and intraoperative data, and postoperative outcomes were collected. Propensity-weighted analysis was used to estimate the effect of robotic versus laparoscopic surgery on outcomes.Of 3845 patients meeting inclusion criteria, 2681 (70%) underwent a laparoscopic approach and 1164 (30%) underwent a robotic approach. Patients undergoing a robotic procedure were more likely to be older, have higher American Society of Anesthesiologists scores, low rectal tumors, and have undergone chemotherapy or radiation before surgery. After propensity adjustment, a robotic approach was associated with a decrease in conversion to open operation (estimated mean difference, -6.7%; P 0.01), length of stay (-0.6 d; P = 0.01), occurrence of postoperative ileus (-3.7%; P = 0.01), and an increase in operative time (20.3 min; P 0.01).Using data from a national cohort, we found that compared with laparoscopy, robotic proctectomy is associated with decreased conversion to open operation, longer operation time, decreased length of stay, and decreased postoperative ileus. Our study identified several advantages to a robotic approach; however, further work is needed to assess cost-effectiveness in conjunction with clinical outcomes.

Background Camel production in Saudi Arabia is severely affected by various diseases and by inadequate veterinary services. Ticks and tick-borne pathogens (TBPs) affect the health and wellbeing of camels consequently diminishing their productivity and performances. In addition, camels may act as hosts for TBPs (e.g. Anaplasma phagocytophilum) causing diseases in humans. The current study aimed to determine the prevalence of ixodid ticks and molecularly investigate the associated pathogens in camels from Saudi Arabia. Methods Blood and tick samples were collected from camels (n = 170) in Riyad Province of Saudi Arabia. Ticks were morphologically identified, and blood of camels were molecularly screened for apicomplexan (i.e. Babesia spp., Theileria spp., Hepatozoon spp.) and rickettsial parasites (i.e. Ehrlichia spp. and Anaplasma spp.). Results Of the 170 camels examined, 116 (68.2%; 95% CI: 60.9–75.1%) were infested by ticks with a mean intensity of 2.53 (95% CI: 2.4–2.6). In total of 296 ticks collected, Hyalomma dromedarii was the most prevalent (76.4%), followed by Hyalomma impeltatum (23.3%) and Hyalomma excavatum (0.3%). Of the tested animals, 13 (7.6%; 95% CI: 4.3–12.8%) scored positive to at least one TBP, with Anaplasma platys (5.3%; 95% CI: 2.7–9.9%) being the most prevalent species, followed by Anaplasma phagocytophilum, Anaplasma sp., Ehrlichia canis and Hepatozoon canis (0.6% each; 95% CI: 0.04–3.4%). None of the camels were found to be co-infected with more than one pathogen. All samples tested negative for Babesia spp. and Theileria spp. Conclusions The present study reveals the occurrence of different tick species and TBPs in camels from Saudi Arabia. Importantly, these camels may carry A. phagocytophilum and A. platys, representing a potential risk to humans.

On November 24, 2017, a change in lung allocation policy was initiated to replace the donor service area with a 250-nautical-mile radius circle around the donor hospital. We aim to analyze the consequences of this change, including organ acquisition cost and transplant outcomes, at the national level.Data on adult patients undergoing lung transplantation between April 27, 2017, and June 22, 2018 (30 weeks before to 30 weeks after allocation policy change) were extracted from the Scientific Registry of Transplant Recipients database. Patients were classified into pre-change and post-change subgroups. Six-month overall survival was evaluated by Kaplan-Meier analysis. Organ acquisition costs were compared between the pre-change and post-change groups.Of the 3317 adult patients removed from the waiting list during the study period (pre-change 1637 vs post-change 1680), 2734 underwent transplantation (pre-change 1371 of 1637 [83.8%] vs post-change 1363 of 1680 [81.1%]), and 382 died or became too sick to be transplanted (pre-change 168 of 1637 [10.3%] vs post-change 214 of 1680 [12.7%], P = .077). Six-month survival rates of transplanted patients were similar between the two groups. However, average organ acquisition costs increased after policy change (pre-change $50,735 ± $10,858 vs post-change $53,440 ± $10,247, P.001) with an increase in nonlocal donors (pre-change 44.3% vs post-change 68.9%, P.001).Organ acquisition costs and resource utilization increased with the new lung allocation policy, whereas deaths on the waiting list or after transplantation did not decrease. Further optimization of the allocation policy is necessary to balance access to transplant and proper stewardship of human and financial resources.

Background: Systemic sclerosis (SSc) is a connective tissue disorder which key feature is a fibrotic process. The role of Endothelin-1 (ET-1) and T-helper (Th)-1 cells in lung and skin fibrosis is well known, although Th17- and Treg-cells were found to be involved. However, no studies analyzed cytokines expression in gastric-juice of SSc patients. Our study aimed to evaluate proinflammatory and profibrotic cytokines in gastric-juice of SSc patients and to investigate their correlations with esophageal dysmotility. Methods: Patients performed upper-gastrointestinal-endoscopy with gastric-juice collection, esophageal manometry and thoracic CT-scan. GM-CSF, ET-1, Th-1 (IFN-&gamma, IL-1&beta, TNF-&alpha, IL-2, IL-6, IL-9), Th-17 (IL-17, IL-21, IL-22, IL-23) and T-reg (IL-10, TGF-&beta, ) related cytokines were measured in 29 SSc-patients and 20 healthy-controls. Results: Patients showed significant lower levels of IL-6, IL-17, IL-22 and ET-1 (p &lt, 0.005) compared with controls. Patients with atrophic gastritis presented significant lower levels of IL-2, IL-9, IL-6, TGF-&beta, GM-CSF, IL-17 and ET-1 (p &lt, 0.005) compared to patients without gastritis. Increased values of IL-2, IL-9, IL-1&beta, IL-17, ET-1 and GM-CSF (p &lt, 0.005) were observed in patients with esophageal impairment. This is the first report of cytokines measurement in gastric juice of patients with SSc. The high IL-17 concentrations in gastric-juice of scleroderma patients with esophageal dysmotility support the signature of Th-17 cells in scleroderma esophageal fibrosis.

Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancreatic disorders. We investigated, by 1H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1+ T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1+ CD8 tumor–infiltrating lymphocytes differentially infiltrated PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase (Pfkm) gene displayed a decrease in PD-1+ cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contribute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.

Rationale: Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2. Hence, this study aims to compare type I IFN response and T cell activation levels between a SARS-CoV-2/HIV-1-coinfected female patient and age-matched HIV-1-positive or uninfected women. Patient concerns: A 52-year-old woman diagnosed with SARS-CoV-2/HIV-1 coinfection, ten HIV-1-positive women and five age-matched-healthy individuals were enrolled in this study. Diagnoses: SARS-CoV-2 infection caused severe pneumonia in the second week of illness in HIV-1-positive patient under protease inhibitors. Chest high-resolution computed tomography images of the SARS-CoV-2/HIV-1-coinfected patient showed bilateral ground-glass opacities. Interventions: SARS-CoV-2/HIV-1-coinfected female patient under darunavir/cobicistat regimen received a 7-days hydroxychloroquine therapy. Analysis of IFNα/β mRNA levels and CD4 and CD8 T cell (CD38, human leukocyte antigen-DR [HLA-DR], CD38 HLA-DR) frequencies were performed by RT/real-time PCR assays and flow cytometry, respectively. Median relative difference (MRD) was calculated for each immunological variable. For values greater than reference, MRD should be a positive number and for values that are smaller, MRD should be negative. Outcomes: The severe pneumonia observed in SARS-CoV-2/HIV-1-positive patient under protease inhibitors was reversed by a 7-days hydroxychloroquine therapy. At the end of treatment, on day 7, patient reported resolution of fever, normalization of respiratory rate (14 breaths/min), and improved oxygen arterial pressure with a FiO2 of 30%. MRD values for IFNα/β and CD4 and CD8 T cells expressing CD38 and/or HLA-DR found in SARS-CoV-2-/HIV-1-coinfected woman were approximatively equal to 0 when refereed respectively to HIV-1-positive female patients [MRDs IFNα/β: median −0.2545 (range: −0.5/0.1); T cells: median −0.11 (range: −0.8/1.3)] and ≥ 6 when referred to healthy individuals [MRDs IFNα/β: median 28.45 (range: 15/41.9); T cells: median 10 (range 6/22)]. Lessons: These results indicate that SARS-CoV-2 infection in HIV-1-positive female patient was associated with increased levels of IFNα/β-mRNAs and T cell activation compared to healthy individuals.