Metabolic memory in diabetic foot syndrome (DFS): MICRO-RNAS, single nucleotide polymorphisms (SNPs) frequency and their relationship with indices of endothelial function and adipo-inflammatory dysfunction.

BACKGROUND: Diabetic foot is a significant cause of morbidity in diabetic patients, with a rate that is approximately twice that of patients without foot ulcers. "Metabolic memory" represents the epigenetic changes induced by chronic hyperglycaemia, despite the correction of the glucose levels themselves. These epigenetic modifications appear to perpetuate the damage caused by persistently elevated glucose levels even in their absence, acting at various levels, mostly affecting the molecular processes of diabetic ulcer healing. METHODS: The aim of our cross-sectional study was to analyse a cohort of patients with diabetes with and without lower limb ulcers. We examined the effects of epigenetic changes on miRNA 126, 305, and 217 expression and the frequency of the SNPs of genes encoding inflammatory molecules (e.g., IL-6 and TNF-alpha) and their correlations with serum levels of proangiogenic molecules (e.g., ENOS, VEGF and HIF-1alpha) and several adipokines as well as with endothelial dysfunction, assessed noninvasively by reactive hyperaemia peripheral artery tonometry. Between March 2021 and June 2022, 110 patients were enrolled into the study: 50 diabetic patients with diabetic foot injuries, 40 diabetic patients without ulcerative complications and 20 nondiabetic patients as the control group. RESULTS: Diabetic subjects with lower limb ulcerative lesions exhibited higher levels of inflammatory cytokines, such as VEGF (191.40 ± 200 pg/mL vs. 98.27 ± 56.92 pg/mL vs. 71.01 ± 52.96 pg/mL; p = 0.22), HIF-1alpha (40.18 ± 10.80 ng/mL vs. 33.50 ± 6.16 ng/mL vs. 33.85 ± 6.84 ng/mL; p = 0.10), and Gremlin-1 (1.72 ± 0.512 ng/mL vs. 1.31 ± 0.21 ng/mL vs. 1.11 ± 0.19 ng/mL; p < 0.0005), than those without lower limb ulcers and healthy controls. Furthermore, we observed that miR-217-5p and miR-503-5p were 2.19-fold (p < 0.05) and 6.21-fold (p = 0.001) more highly expressed in diabetic foot patients than in healthy controls, respectively. Additionally, diabetic patients without lower limb ulcerative complications showed 2.41-fold (p = 0) and 2.24-fold (p = 0.029) higher expression of miR-217-5p and miR-503-5p, respectively, than healthy controls. Finally, diabetic patients with and without ulcerative complications of the lower limbs showed higher expression of the VEGFC2578A CC polymorphism (p = 0.001) and lower expression of the VEGFC2578A AC polymorphism (p < 0.005) than the healthy control population. We observed a significant increase in Gremlin-1 levels in patients with diabetic foot, suggesting that this inflammatory adipokine may serve as a predictive marker for the diagnosis of diabetic foot. CONCLUSIONS: Our results highlighted that patients with diabetic foot showed predominant expression of the VEGF C2578A CC polymorphism and reduced expression of the AC allele. Additionally, we found an overexpression of miR-217-5p and miR-503-5p in diabetic patients with and without diabetic foot syndrome compared with healthy controls. These results align with those reported in the literature, in which the overexpression of miR-217-5p and miR-503-5p in the context of diabetic foot is reported. The identification of these epigenetic modifications could therefore be helpful in the early diagnosis of diabetic foot and the treatment of risk factors. However, further studies are necessary to confirm this hypothesis.

Methadone as First-line Opioid for the Management of Cancer Pain.

AIM: The aim of this study was to assess the efficacy and adverse effects of methadone when used as first-line therapy in patients that are either receiving low doses of opioids or none. METHODS: Patients with advanced cancer were prospectively assessed. Opioid-naive patients (L-group) were started with methadone at 6 mg/day. Patients receiving weak or other opioids in doses of <60 mg/day of OME (H-group) were started with methadone at 9 mg/day. Methadone doses were changed according to the clinical needs to obtain the most favorable balance between analgesia and adverse effects. Edmonton Symptom Asssement Score (ESAS), Memorial Delirium Assessment Score (MDAS), doses of methadone, and the use of adjuvant drugs were recorded before starting the study treatment (T0), 1 week after (T7), 2 weeks after (T14), 1 month after (T30), and 2 months after (T60). Methadone escalation index percent (MEI%) and in mg (MEImg) were calculated at T30 and T60. RESULTS: Eighty-two patients were assessed. In both groups H and L, there were significant changes in pain and symptom intensity at the different times during the study. Adverse effects as causes of drop-out were minimal. Mean MEImg was 0.09 (SD 0.28) and 0.02 (SD 0.07) at T30 and T60, respectively. MEI% was 1.01 (SD 3.08) and 0.27 (SD 0.86) at T30 and T60, respectively. CONCLUSION: Methadone used as a first-line opioid therapy provided good analgesia with limited adverse effects and a minimal opioid-induced tolerance.

Conversion ratios for opioid switching: a pragmatic study.

BACKGROUND: The final conversion ratios among opioids used for successful switching are unknown. The aim of this study was to determine the initial and final conversion ratios used for a successful opioid switching in cancer patients, and eventual associated factors. METHODS: Ninety-five patients who were successfully switched were evaluated. The following data were collected: age, gender, Karnofsky performance score, primary cancer, cognitive function, the presence of neuropathic, and incident pain. Opioids, route of administration, and their doses expressed in oral morphine equivalents used before OS were recorded as well as opioids use for starting opioid switching, and at time of stabilization. Physical and psychological symptoms were routinely evaluated by Edmonton Symptom Assessment Scale. RESULTS: No statistical changes were observed between the initial conversion ratios and those achieved at time of stabilization for all the sequences of opioid switching. When considering patients switched to methadone, there was no association between factors taken into considerations. CONCLUSION: Opioid switching is a highly effective and safe technique, improving analgesia and reducing the opioid-related symptom burden. The final conversion ratios were not different from those used for starting opioid switching. Patients receiving higher doses of opioids should be carefully monitored for individual and unexpected responses in an experienced palliative care unit, particularly those switched to methadone. Future studies should provide data regarding the profile of patients with difficult pain to be hospitalized.

Pattern and characteristics of patients admitted to a hospice connected with an acute palliative care unit in a comprehensive cancer center.

PURPOSE: Information about inpatient hospice activity is limited. No data exist about the pattern and the characteristics of advanced cancer patients admitted to a hospice connected to an acute supportive/palliative care unit (ASPCU). METHODS: Data of hospice admissions were retrieved from the database where all data were prospectively collected. The Edmonton Symptom Assessment Scale (ESAS) and the use of analgesics and adjuvant were recorded at admission (T0), 1 week (T7), 2 weeks (T14), and the day before death (T-end). The use of palliative sedation and its indication, duration, and drugs end doses used were recorded. The number of hospice deaths, discharges, and hospice staying were recorded. RESULTS: One hundred seventy-seven patients were admitted in 13 months. There were significant differences in total ESAS at T0 (P = 0.033), total ESAS being significantly lower in patients admitted from the ASPCU than those referred from other settings. The day before death (T-end), only 48 patients could be evaluated. Patients referred by a palliative care setting were more likely to be prescribed opioids at T0 (P = 0.0007). At T-end, there was a significant increase in the use of morphine and haloperidol (P < 0.05). Seventeen percent of patients died within 48 h. Only a minority of patients could be properly assessed at T-end (25%). Palliative sedation was performed in 10.1% of patients. The mean hospice staying was 16.3 (SD 21.4) days. There were no differences in mean hospice staying between patients who died in hospice or those discharged (P = 0.873). CONCLUSION: The presence of a hospice in a comprehensive cancer center could offer a further opportunity for continuing care. Specialized palliative care may be offered to patients referred from other hospitals, home palliative care, but above all, transfer to hospice may allow a continuity of care for those patients who were initially admitted to an ASPCU for symptom control, to which anticancer therapies were withdrawn or withhold after multidisciplinary consultation. Similarly, after a proper palliative care consultation in other hospital units, patients may be referred to hospice. This process may avoid transfers to external hospices, which can prevent the continuity of care.

The use of complementary alternative medicines in advanced cancer patients followed at home.

OBJECTIVES: To assess the use of complementary alternative medicines (CAM) in advanced cancer patients followed at home. METHODS: A consecutive sample of advanced cancer patients admitted to a home palliative care program was invited to participate in the study in a period of two months. Demographic characteristics, religious belief, education level, diagnosis, and socio-economic condition were recorded. Patients were asked about the use of CAM, considered to be a health-related treatment practiced outside the established health services. Information about CAM indications and those who prescribed or suggested CAM were also collected. RESULTS: Two hundred and eighty-three advanced cancer patients followed at home were surveyed. Twelve patients (4.2%) were receiving CAM. The indication and type of CAM were variable, as well as the costs. Given the low number of patients taking CAM, no further analysis was performed. CONCLUSION: A limited number of advanced cancer patients followed at home were using CAM. Further multicenter studies with a larger sample should be performed to provide information about such therapies, also including eventual benefits.

Decline in hospitalization rates for herpes zoster in Italy (2003-2018): reduction in the burden of disease or changing of hospitalization criteria?

BACKGROUND: Herpes Zoster (HZ) is a very demanding disease caused by the reactivation of latent Varicella Zoster Virus. The main aim of this study was to estimate the burden of the HZ hospitalizations in Italy from 2003 to 2018 evaluating temporal trends. METHODS: Retrospective population-based study analyzing Hospital Discharge Records. Hospitalization records reporting the ICD-9 CM 053.X code in the principal diagnosis or in any of the five secondary diagnoses were considered as cases. Trends of hospitalization rates have been evaluated by Joinpoint analyses. RESULTS: Overall, 99,036 patients were hospitalized with HZ in the 16-year period of the study, and 83,720 (84.5%) of these patients were over 50 years. Hospitalization rate was 10.4 per 100,000 persons/year with a significant decreasing trend from 13.9 in 2003-2006 to 7.8 in 2015-2018 (p < 0.001). Hospitalization rates showed a 20-fold higher risk among subjects aged over 80 years and 11-fold higher risk among 70-79-year-old subjects with respect to those aged less than 50 years. Over time, a statistically significant increase was observed for the case fatality rate (from 1.2 to 1.7%; p < 0.001) and the median length of stay (from 7 to 8 days; p < 0.001). CONCLUSIONS: Zoster is a disease that causes hospitalization as relatively frequent complication and the observed reduced trend over time could be due to a restriction in hospitalization criteria instead of a reduced burden of disease. The decreasing trend should be carefully interpreted, since it could have an impact on promoting herpes zoster vaccination.

Polypoidal choroidal vasculopathy in pachychoroid: combined treatment with photodynamic therapy and aflibercept.

INTRODUCTION: To evaluate the effects of combined therapy using intravitreal Aflibercept (IVA) and photodynamic therapy (PDT) on polypoidal choroidal vasculopathy related to pachychoroid disease (PPCV). METHODS: Patients with PPCV were treated with PDT combined with 3 IVA injections on a monthly basis, followed by pro re nata criteria. The 12-month follow-up consisted of multiple revaluations of visual acuity and SS-OCT parameters of clinical activity. RESULTS: Nineteen eyes were included in the study; mean age was 65.5 years. Visual acuity improved after 12 months (0.35 ± 0.25 to 0.2 ± 0.20 logMAR, p = 0.005). Percentage of eyes with intraretinal and subretinal fluid reduced from baseline to the 12-month follow-up (from 52.6 to 10.5%, p = 0.12, and from 89.5 to 5.3% p = 0.0009, respectively). Central retinal and mean macular thicknesses reduced (258 ± 39.6 to 204.8 ± 38.8 µm p = 0.04 and 293.8 ± 32.1 to 248.1 ± 29.6 µm p = 0.017, respectively). Central choroidal and mean choroidal thicknesses also displayed a reduction (328.6 ± 54.9 to 289.8 ± 44.6 µm p = 0.001 and 314.5 ± 55.3 to 287.9 ± 47.6 µm p = 0.015, respectively). The mean number of injections was 4.6/year. CONCLUSION: The results support the use of a combined therapy with Aflibercept and PDT in PPCV. This treatment would act in synergy, with anti-VEGF controlling exudation and PDT closing the aneurysmal vessel and reducing choroidal congestion.

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction.

BACKGROUND: Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. AIMS: The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices. METHODS: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection. RESULTS: 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance. DISCUSSION: Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: a randomized trial.

BACKGROUND: Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage. AIMS: We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditional antidiabetic treatment compared with traditional antidiabetic treatment alone in subjects with type 2 diabetes. METHODS: Men and women (aged ≥ 50 years) with established or newly detected type 2 diabetes whose HbA1c level was 9.5% or less on stable doses of up to two oral glucose- lowering drugs with or without basal insulin therapy were eligible for randomization. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness (PWV: pulse wave velocity and augmentation index) and endothelial function (RHI: reactive hyperaemia index) were evaluated at baseline and at three-month and nine-month examination visits. At each visit (at 3 and 9 months), the subjects were also evaluated for glycaemic variables such as fasting plasma glucose (FPG) and HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels. RESULTS: At the three-month follow-up, the subjects treated with dulaglutide showed significantly lower serum levels of FPG and HbA1c than control subjects treated with conventional therapy. At the 9-month follow-up, subjects treated with dulaglutide showed significant lower values of the mean diastolic blood pressure, BMI, total serum cholesterol, LDL cholesterol, FPG, HbA1c and PWV and higher mean RHI values than control subjects treated with conventional therapy. CONCLUSIONS: Our randomized trial showed that subjects with type 2 diabetes treated with conventional therapy plus 1.5 mg/day of subcutaneous dulaglutide compared with subjects treated with conventional therapy alone showed favourable metabolic effects associated with positive effects on vascular health markers such as arterial stiffness and endothelial function markers. These findings are consistent with previous study findings indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.

Financial distress and its impact on symptom expression in advanced cancer patients.

AIM: To assess financial distress (FD) and its impact on symptom expression and other quality of life issues PATIENTS AND METHODS: Advanced cancer patients admitted to inpatient and outpatient clinics were selected. Standard epidemiological data including age, gender, primary cancer diagnosis, and Karnofsky level were recorded. Data regarding marital status, number of cohabitants, religious belief, educational level, and family income (< 1000, 1000-3.000, > 3000 euros), as well as extra costs not covered by health care system, were collected. Symptom burden including FD was measured by Edmonton Symptom Assessment Scale (ESAS), FACT-G (Functional Assessment of Cancer Therapy-General), and HADS (Hospital Anxiety Depression scale) were measured. RESULTS: Two hundred thirty-six patients were evaluated. The mean FD was 3.55 (SD 3.1). One hundred patients (42%) had a FD of ≥ 4. There was an inverse correlation between FD and income (P = 0.032). Most patients incurred in extra-costs, the most frequent being for drugs (n, 114). FD was inversely associated with age (P = 0.024), marital status (divorced or separated, P = 0.005), ESAS anxiety (P = 0.006), total ESAS (P = 0.019), physical well-being (P = 0.033), poor social family well-being (P = 0.004), emotional well-being (P = 0.045), poor functional well-being (P = 0.019), HADS-A (P = 0.003), and global HADS (P = 0.034). Family income was inversely related to age (P = 0.023), education level (P < 0.0005), less number of hospital admissions in the last month (P = 0.020), physical well-being (P = 0.039), social/family well-being (P = 0.020), and total well-being (P = 0.001). CONCLUSION: FD is very common in advanced cancer patients. FD was associated with anxiety, depression, and poor quality of life. The screening of FD may allow to develop effective interventions of social support.

The lower the expectations in controlling the symptoms of advanced cancer patients, the better the clinical response.

AIM: The aim of this study was to compare patients' global impression (PGI) and the achievement of personalised symptom goal response (PSGR), after a comprehensive palliative care treatment in advanced cancer patients having high (HPSG) and low symptom goals (LPSG). PATIENTS AND METHODS: Advanced cancer patients admitted to palliative care units rated symptoms intensity by the Edmonton Symptom Assessment Score (ESAS) at admission and then after one week of comprehensive palliative care treatment. For each symptom, patients were divided into two groups, according to their patient symptom goal (PSG): ≥4 (HPSG), and 0-2 (LPSG). PGI and PSGR were evaluated after one week of palliative care. The Memorial Delirium Assessment Scale (MDAS) was assessed at admission. RESULTS: After one week of palliative care, changes in ESAS items were significantly larger in the HPSG group. HPSG patients had a better PGI and reached their target more frequently than LPSG patients for pain, weakness, and poor well-being. LPSG patients were more likely to obtain their target for appetite and insomnia. HPSG patients were more likely to have a lower Karnofsky, a lower educational level, older age, or higher MDAS values for the different ESAS items. CONCLUSION: Advanced cancer patients with low expectations (HPSG) were more likely to achieve their PSGR after a comprehensive palliative care treatment, reporting also a better PGI for some leading symptoms such as pain, weakness, and poor well-being. More fragile patients seem to have lower expectations and to be more likely to be satisfied.

Bilateral Ultrathin Descemet's Stripping Automated Endothelial Keratoplasty vs. Bilateral Penetrating Keratoplasty in Fuchs' Dystrophy: Corneal Higher-Order Aberrations, Contrast Sensitivity and Quality of Life.

Background and Objectives: The objective of this paper is to compare the visual outcomes and quality of life (QoL) after bilateral ultrathin Descemet's stripping automated endothelial keratoplasty (UT-DSAEK) with bilateral penetrating keratoplasty (PK) for Fuchs' endothelial dystrophy (FED). Materials and Methods: Retrospective comparative cohort study, including 11 patients with FED who underwent bilateral PK and 13 patients with FED who underwent bilateral UT-DSAEK. All patients were already pseudophakic or had undergone a combined cataract procedure. The main outcomes were corrected distance visual acuity (CDVA) corneal higher-order aberrations (HOAs), contrast sensitivity (CS) and quality of life (QoL). Results: The mean follow-up after the second eye surgery was 32.5 ± 10.2 months in PK and 19.6 ± 8.6 months in UT-DSAEK patients. The CDVA in the UT-DSAEK group was significantly better than in the PK one (0.18 ± 0.07 vs. 0.35 ± 0.16 logMAR, p < 0.0001). The mean anterior corneal total HOAs of the central 5 mm were significantly lower in UT-DSAEK eyes than in PK eyes (0.438 ± 0.078 µ and 1.282 ± 0.330 µ respectively, p < 0.0001), whilst the mean posterior total HOAs did not differ between groups (0.196 ± 0.056 µ and 0.231 ± 0.089 µ, respectively, p = 0.253). The CS was lower at 0.75 and 1.5 cycles/degree in P the K group when compared to the DSAEK one (p = 0.008 and 0.005, respectively). The QoL scores by the NEI RQL-42 test exhibited better values in DSAEK patients in 9 out of 13 scales. Conclusion: Our study confirms that UT-DSAEK provides a better visual function in terms of CDVA and CS, together with lower HOAs, when compared to PK. Hence, the vision-related QoL, binocularly evaluated by the NEI RQL-42 items, indicates a higher satisfaction in UT-DSAEK eyes.

Barriers and Adherence to Pain Management in Advanced Cancer Patients.

AIM: To assess patients' barriers to pain management and analgesic medication adherence in patients with advanced cancer. METHODS: This was a prospective cross-sectional study in patients with advanced cancer receiving chronic opioid therapy. Age, gender, cancer diagnosis, Karnofsky level, and educational status were recorded. The Brief Pain Inventory (BPI), Edmonton Symptom Assessment Scale (ESAS), Memorial Delirium Assessment Scale (MDAS), Barriers Questionnaire II (BQ-II), Medication Adherence Rating Scale (MARS), and Hospital Anxiety and Depression Scale (HADS) were the measurement instruments used. RESULTS: One-hundred-thirteen patients were analyzed. The mean age was 68 (±13) years, and 59 (52%) were male. The mean Karnofsky status was 51.4 (standard deviation [SD] 11.5). The mean score for BQ-II items was 1.77 (SD 0.7). The BQ-II score was independently related to the HADS-Depression score (P = 0.033) and the total HADS score (P = 0.049). Negative side-effects and attitudes toward psychotropic medication globally prevailed among MARS items. These items were independently associated with gender (P = 0.030), pain (P = 0.003), and depression (P = 0.047). CONCLUSION: Barriers to pain management were mild. Psychological factors such as depression were the main factor associated with barriers. Poor adherence to analgesic medication was mostly manifested as negative side-effects and attitudes toward psychotropic medication, was more frequent observed in females, and was associated with the ESAS items pain and depression.

Effects of age and gender in patients receiving doses of opioids for breakthrough pain proportional to background opioid doses.

AIM: To identify the role of age and gender in analgesic and adverse effects after administering fentanyl products for breakthrough pain (BT), given in doses proportional to opioid doses given for background pain. METHODS: Data from nine studies, in which patients with BP were given fentanyl products in doses proportional to their basal opioid regimen, were analyzed. RESULTS: A total 462 patients presenting 1905 episodes of BP were included in this analysis. In older patients, the decrease in pain intensity was more pronounced 15 min after administration of a BP medication. No gender differences were found. No significant differences in frequency and intensity of adverse effects for age and gender were found. CONCLUSION: Fentanyl products given for BP in doses proportional to background opioid regimen were more effective in older patients without adding risks of adverse effects. Gender did not influence analgesia and adverse effects of fentanyl products.

Association between alcoholism and symptom expression, patient symptom goals, and clinical response in advanced cancer patients.

AIM: The aim of this study was to determine the influence of alcoholism on symptom expression, personalized symptom goal (PSG) and patient goal response (PGR), and patient global impression (PGI) in advanced cancer patients. METHODS: This was a secondary analysis of an international multicenter study. Advanced cancer patients who had a history of alcohol dependence positive, according to CAGE (cut down, annoy, guilt, eye-opener), were selected. Thirty patients (3.45%) were CAGE-positive. This sample was matched with 30 patients with similar characteristics who were CAGE-negative. Patients rated symptom intensity by using the Edmonton Symptom Assessment Score (ESAS) at admission (T0) and then after 1 week. For each symptom, patients reported their PSG. After a week of comprehensive palliative care, PSG was measured again (T7), as well as the achievement of PGR, and PGI. Minimal clinically important difference (MCID) was calculated by PGI of improvement or deterioration at T7 (bit better or a little worse, respectively). RESULTS: A significant decrease in intensity was found for most symptoms in both groups. In CAGE-negative and CAGE-positive patients, most patients had a PSG of ≤ 3 for all ESAS items as a target at T0. All PSG targets did not changed significantly after 1 week of palliative care in both groups. Although CAGE-positive basically had unfavorable PGI and PGR, a statistical significance was achieved only for appetite (P = 0.037; ANOVA test). In CAGE-negative patients, Karnofsky was the only factor independently associated with PGI for pain and dyspnea. Factors independently associated with PGI for nausea were symptom intensity at T0 and home situation. In CAGE-positive patients, Karnofsky was independently associated with PGI for pain, nausea, and well-being. Symptom intensity at T0 was independently associated with PGI for weakness. CONCLUSION: CAGE-positive advanced cancer patients favorably responded to a palliative care intervention. No greater differences have been found in comparison with CAGE-negative patients for PSG, PGR, and PGI, except for appetite. Further studies with large number of patients could confirm some trends observed in this study.

Personalized goal for insomnia and clinical response in advanced cancer patients.

AIM: The aim of this study was to assess the Personalized Insomnia Intensity Goal (PIIG), the achievement of Personalized Goal Response (PGR), and Patient Global Impression (PGI) after a comprehensive symptom management. PATIENTS AND METHODS: Advanced cancer patients admitted to palliative care units rated pain and symptoms intensity and their PIIG by using the Edmonton Symptom Assessment Score (ESAS) (T0). In patients with significant levels of insomnia, the achievement of target expected (PIIG) was measured (patient goal response, PIGR), as well the patient global impression (PGI), by the minimal clinically important difference (MCID), after a comprehensive symptom management (T7). RESULTS: Three hundred ninety-seven patients with a level of insomnia of ≥ 3 on ESAS were analyzed in this study. The mean values of PIIG at T0 and T7 were 1.2 (SD 1.5) and 0.9 (SD 1.4), respectively. Most patients (n = 406, 89.8%) indicated a PIIG of ≤ 3 as a target at T0. Such target was significantly lower at T7 (p = < 0.0005). PGI, expressed as MCID, was perceived with a mean decrease in insomnia intensity of - 2.3. In a minority of patients (n = 26; 5.8%) insomnia worsened, with a MCID of 0.50 (SD 2.8). Higher insomnia intensity at T0 and lower insomnia intensity at T7 were independently related to PGI. PIGR was achieved in 87.9% of patients. PIGR was associated with PIIG at T0, and inversely associated to insomnia intensity at T0 and T7, and PIIG at T7. CONCLUSION: PGIR and PGI seem to be relevant for evaluating the effects of a comprehensive management of insomnia, suggesting therapeutic decisions according to PIIG. Some factors influencing the individual target and clinical response have been detected.

Personalized Pain Goals and Responses in Advanced Cancer Patients.

OBJECTIVE: To assess the personalized pain intensity goal (PPIG), the achievement of a personalized pain goal response (PPGR), and patients' global impression (PGI) in advanced cancer patients after a comprehensive pain and symptom management. DESIGN: Prospective, longitudinal. SETTING: Acute pain relief and palliative/supportive care. SUBJECTS: 689 advanced cancer patients. METHODS: Measurement of Edmonton Symptom Assessment Score (ESAS) and personalized pain intensity goal (PPIG) at admission (T0). After a week (T7) personalized pain goal response (PPGR) and patients' global impression (PGI) were evaluated. RESULTS: The mean PPIG was 1.33 (SD 1.59). A mean decrease in pain intensity of - 2.09 was required on PPIG to perceive a minimal clinically important difference (MCID). A better improvement corresponded to a mean change of - 3.41 points, while a much better improvement corresponded to a mean of - 4.59 points. Patients perceived a MCID (little worse) with a mean increase in pain intensity of 0.25, and a worse with a mean increase of 2.33 points. Higher pain intensity at T0 and lower pain intensity at T7 were independently related to PGI. 207 (30.0%) patients achieved PPGR. PPGR was associated with higher PPIG at T0 and T7, and inversely associated to pain intensity at T0 and T7, and Karnofsky level. Patients with high pain intensity at T0 achieved a favorable PGI, even when PPIG was not achieved by PPGR. CONCLUSION: PPIG, PPGR and PGI seem to be relevant for evaluating the effects of a comprehensive management of pain, assisting decision-making process according to patients' expectations. Some factors may be implicated in determining the individual target and the clinical response.

Infracyanine Green vs. Brilliant Blue G in Inverted Flap Surgery for Large Macular Holes: A Long-Term Swept-Source OCT Analysis.

Background and Objectives: To compare the long-term toxicity of infracyanine green (IFCG) to brilliant blue G (BBG) in inverted internal limiting membrane flap surgery (I-ILMFS) for large, full-thickness macular holes (FTMHs). Materials and Methods: Prospective randomized study including 39 eyes with ≥ 400 µm idiopathic FTMH who underwent I-ILMFS with either IFCG or BBG. Postoperative 6- and 12-month corrected distance visual acuity (CDVA), closure rate, and swept-source optical coherence tomography parameters, including ellipsoid zone (EZ) and external limiting membrane (ELM) mean defect length, central foveal thicknesses (CFT), parafoveal macular thickness (MT), ganglion cells and inner plexiform layer (GCL++) thickness, and peripapillary nerve fiber layer (pRNFL) thickness, were compared. Results: Nineteen eyes were included in the IFCG group and 20 eyes in the BBG group. In all cases a FTMH closure was found. CDVA improved at 6 and 12 months in both groups (p < 0.0005); the increase at 12 months was greater in the BBG group (p = 0.036). EZ and ELM defects did not differ between groups at either follow-up time. CFT at 12 months was greater in the BBG group (p = 0.041). A 12-months compared to 6-months MT decrease was present in both groups (p < 0.01). The GCL++ superior inner sector was thicker in the BBG group at 12 months (p = 0.036), as were the superior outer sector (p = 0.039 and p = 0.027 at 6 and 12 months, respectively) and inferior outer sector (p = 0.011 and p = 0.009 at 6 and 12 months, respectively). Conclusion: In our study BBG in I-ILMFS exhibits better long-term CDVA and retinal thickness than does IFCG, suggesting a lesser toxicity from BBG. These findings support the use of BBG over IFCG in I-ILMFS.

Symptom Expression in Patients with Advanced Cancer Admitted to an Acute Supportive/Palliative Care Unit With and Without Delirium.

AIM: The aim of this study was to investigate the relationship between delirium and symptom expression in patients with advanced cancer admitted to an acute supportive/palliative care unit (ASPCU). METHODS: A consecutive sample of patients with advanced cancer who were admitted to an ASPCU was prospectively assessed for a period of 10 months. The Edmonton Symptom Assessment Scale (ESAS) and the MDAS (Memorial Delirium Assessment Scale) were measured at admission (T0) and after 7 days of palliative care (T7). RESULTS: Two hundred forty-six patients had complete data regarding MDAS measurements, at either T0 and T7. Of these, 75 (30.5%) and 63 patients (25.6%) had delirium at T0 and after a week of palliative care (T7), with a decrease in the frequency of delirium of 4.9% (from 30.5% to 25.6%); that means that 16% of patients with delirium improved their cognitive status after initiation of palliative care. Intensities of pain, depression, poor well-being, and global ESAS were significantly higher in patients with delirium. Patients who did not have delirium at T0 but developed delirium during admission after 1 week of palliative care had a higher level of symptom expression for pain, weakness, nausea, anxiety, dyspnea, appetite, and consequently global ESAS. Patients who did not develop delirium at any time had a relevant decrease in intensity of all ESAS items after 1 week of palliative care. The decrease of symptom intensity was significant for pain, insomnia, appetite, poor well-being, and global ESAS in patients with delirium either at T0 and T7, although these differences were less relevant than those observed in patients without delirium. In patients with delirium at T0 who improved their cognitive function at T7 (no delirium), significant changes were found in most ESAS items. CONCLUSION: Symptom expression is amplified in patients with delirium, whereas patients without delirium may be more responsive to palliative treatments with a significant decrease in intensity of ESAS items. IMPLICATIONS FOR PRACTICE: Symptom expression is amplified in patients with cancer who have delirium, whereas patients without delirium may be more responsive to palliative treatments with a significant decrease in symptom intensity.

HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute ischemic stroke.

INTRODUCTION: In humans, a major component of natural killer (NK) and T cell target recognition depends on the surveillance of human leukocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIRs). AIMS: To implement the knowledge about the immunological genetic background of acute ischemic stroke susceptibility in relation to the frequency of the KIR genes and HLA alleles. METHODS: Subjects with acute ischemic stroke and subjects without stroke were genotyped for the presence of KIR genes and of the three major KIR ligand groups, HLA-C1, HLA-C2, and HLA-Bw4, both HLA-B and HLA-A loci. RESULTS: Between November 2013 and February 2016, consecutive patients with acute ischemic stroke were recruited. As healthy controls, we enrolled subjects without acute ischemic stroke. Subjects with acute ischemic stroke in comparison with controls showed a higher frequency of 2DL3, 2DL5B, 2DS2, and 2DS4 KIR genes and a lower frequency of HLA-B-Bw4I alleles. Subjects without acute ischemic stroke showed a higher frequency of interaction between KIR 2DS2 and HLAC2. We also observed a higher frequency of 2DL3 and 2 DL4 KIR genes in subjects with atherosclerotic (LAAS) subtype. Multiple logistic regression analysis showed a protective effect towards stroke of HLA-B-Bw4I and interaction between KIR 2DL2 and HLAC1 and 2DS2-HLAC2 and a detrimental effect of 2DL2-HLA-C1_A interactions. CONCLUSION: Our findings of a higher frequency of activating KIR genes seem to be consistent with findings previously reported patients with coronary syndrome. This higher frequency of "proinflammatory" genes in subjects with ischemic stroke could also explain the immunoinflammatory activation of the acute phase of stroke.