Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer.

PURPOSE: Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because of poor tolerance to therapy. In this study, the role of circulating cytokines in the production symptoms in cancer patients is evaluated. EXPERIMENTAL DESIGN: Eighty patients with metastatic colorectal cancer with either normal (group I, n = 40) or dampened (group II, n = 40) 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy patterns were correlated with QOL indices, serum cortisol obtained at 8:00 a.m. and 4:00 p.m. and with serum levels of transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin 6 (IL-6) obtained at 8:00 a.m. and analyzed in duplicate by ELISA. Cytokine levels and survival were also correlated. RESULTS: Group II patients had significantly higher pre treatment levels of all three cytokines, displayed significantly poorer emotional and social functioning, had higher fatigue, more appetite loss, and poorer performance status compared with group I patients. Transforming growth factor-alpha (TGF-alpha) and IL-6 were significantly increased in the patients with WHO performance status >1 and in those with appetite loss. Fatigue was significantly associated with elevated TGF-alpha only. IL-6 was increased in those patients with extensive liver involvement and multiple organ replacement, and it was significantly correlated with dampened cortisol rhythm. In a multivariate analysis, IL-6 was correlated with poor treatment outcome. CONCLUSIONS: Significant correlations were found between serum levels of TGF-alpha and IL-6, circadian patterns in wrist activity and serum cortisol and tumor-related symptoms in patients with metastatic colorectal cancer. These data support the hypothesis that some cancer patient's symptoms of fatigue, poor QOL, and treatment outcome are related to tumor or host generated cytokines and could reflect cytokine effects on the circadian timing system. This interplay between cytokine signaling pathways, the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and efferent pathways of the suprachiasmatic nucleus that control circadian physiology, opens the way to new rational interventions for symptom management in cancer patients.     

Evolution of the technique and indications of mini-invasive surgery of cholelithiasis

BACKGROUND: A review of the experience with laparoscopic cholecystectomy to evaluate the impact of the efficacy, safety, and complications on the learning curve. Study design: Retrospective study. METHODS: Between 1993 and 1998, 415 patients, 123 males and 292 females, median age 52.1 years (range 23-96 years), with symptomatic cholelithiasis, underwent laparoscopic cholecystectomy. On the basis of different selection criteria and surgical techniques adopted, our experience was divided into two periods (93-95 and 96-98). RESULTS: The success rate was 89.4% (371 patients) with a conversion rate of 10.6% (44 patients). Overall complications rate was 2.9% (12 patients): 7 major complications (2 biliary tract injuries, 2 hemorrhages, 1 sub-phrenic abscess, 1 gastric perforation and 1 choleperitoneum) and 3 minor complications (1 biliary leakage and 2 wound infections) with 2 long-term sequela (umbilical site eventration). Median hospital stay was 3.3 days, 2.2 days for uncomplicated cases and 5.6 in those converted or complicated. Comparison between the two groups showed a conversion rate of 10.6 vs 10.4% (23 vs 21 patients), with a complication rate of 4.2% vs 2.2%. CONCLUSIONS: Laparoscopic cholecystectomy can be considered a safe and effective procedure for the treatment of simple or complicated cholelithiasis. French surgical technique seems to be easier in the management of acute cholecystitis or lithiasis occurring after acute pancreatitis. Specific training in laparoscopy surgery is mandatory to avoid major complications.     

Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients

Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.     

The impact of continuous positive airway pressure on cardiac mechanics: Findings from a meta‐analysis of echocardiographic studies

Current evidence on the effects of continuous positive airway pressure (CPAP) on cardiac mechanics in patients with obstructive sleep apnea (OSA) is based on a few single studies. The authors investigated this topic through a meta‐analysis of speckle tracking echocardiography (STE) studies that provided data on left ventricular (LV) and right ventricular (RV) mechanics as assessed by global longitudinal strain (GLS). The PubMed, OVID‐MEDLINE, and Cochrane library databases were systematically analyzed to search English‐language review papers published from inception to January 31, 2022. Studies were identified by crossing the following terms: “obstructive sleep apnea”, “sleep quality”, “sleep disordered breathing”, “continuous positive airway pressure therapy”, “noninvasive ventilation”, “left ventricular hypertrophy”, “systolic dysfunction”, “global longitudinal strain”, “left ventricular mechanics”, “right ventricular mechanics”, “echocardiography” and “STE echocardiography”. The meta‐analysis, including a total of 337 patients with OSA from nine studies (follow‐up 2–24 months) showed a significant GLS improvement in both LV and RV after CPAP, standard mean difference (SMD) being 0.51±0.08, CI:0.36–0.66, p = .0001 and 0.28±0.07, CI:0.15–0.42, p = .0001), respectively. Corresponding SMD values for LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE) were 0.20±0.06, CI:0.08–0.33, p = .001 and 0.08±0.06, CI: ‐0.04/0.20, p = .21. Our meta‐analysis suggests that: I) CPAP treatment exerts beneficial effects on biventricular function in patients with OSA; II) the assessment of cardiac mechanics by STE should be routinely recommended for monitoring cardiac function in this setting, due to limitations of conventional echocardiography in evaluating biventricular performance.     

Liquid Biopsy at Home: Delivering Precision Medicine for Patients with Cancer During the COVID-19 Pandemic

CoronaVirus disease-2019 has changed the delivery of health care worldwide and the pandemic has challenged oncologists to reorganize cancer care. Recently, progress has been made in the field of precision medicine to provide to patients with cancer the best therapeutic choice for their individual needs. In this context, the Foundation Medicine (FMI)-Liquid@Home project has emerged as a key weapon to deal with the new pandemic situation. FoundationOne Liquid Assay (F1L) is a next-generation sequences-based liquid biopsy service, able to detect 324 molecular alterations and genomic signatures, from May 2020 available at patients’ home (FMI-Liquid@Home). We analyzed time and costs saving for patients with cancer, their caregivers and National Healthcare System (NHS) with FMI-Liquid@Home versus F1L performed at our Department. Different variables have been evaluated. Between May 2020 and August 2021, 218 FMI-Liquid@Home were performed for patients with cancer in Italy. Among these, our Department performed 153 FMI-Liquid@Home with the success rate of 98% (vs. 95% for F1L in the hospital). Time saving for patients and their caregivers was 494.86 and 427.36 hours, respectively, and costs saving was 13 548.70€. Moreover, for working people these savings were 1084.71 hours and 31 239.65€, respectively. In addition, the total gain for the hospital was 163.5 hours and 6785€, whereas for NHS was 1084.71 hours and 51 573.60€, respectively. FMI-Liquid@Home service appears to be useful and convenient allowing time and costs saving for patients, caregivers, and NHS. Born during the COVID-19 pandemic, it could be integrated in oncological daily routine in the future. Therefore, additional studies are needed to better understand the overall gain and how to integrate this service in different countries.     

An open-label, multicentre trial to evaluate the vaginal bleeding pattern of the combined contraceptive vaginal ring NuvaRing

Objective

The objective of this multicentre, non-controlled, open-label study is the evaluation of the bleeding patterns during the use of a vaginal combined contraceptive, its safety in relation to occurrence of adverse effects, its efficacy as a contraceptive method and user compliance.

Study design

Healthy female volunteers (N = 165), asking for contraception, were enrolled to participate in the study. Each subject was given seven vaginal rings, releasing an average amount of 120 μg etonogestrel (ENG) and 15 μg ethinylestradiol (EE) per day. Study period was 7 cycles. A total of 878 cycles was valid for statistical analysis. The primary parameter, (breakthrough bleeding and/or spotting), was recorded for each cycle. The subjects were asked to report any adverse effect experienced during the treatment period, general physical and gynaecological examinations were performed and haematological blood tests were taken.

Results

Breakthrough bleeding/spotting occurred in 5.01% cycles (44 out of 878 cycles, of whom 37 were breakthrough spotting only). Absence of withdrawal bleeding during the ring-free period was reported in 1.94% cycles (17 out of 878). Forty-one subjects (24.8%) reported 66 events that were potentially drug-related. The most frequently drug-related events were weight increase (10 cases), headache (9 cases), nausea (4 cases). No pregnancy was reported during the study period. Haematology and chemical chemistry tests showed no clinically significant abnormality.

Conclusions

In the present study, NuvaRing^® has shown to be a valid contraceptive method to ensure optimal cycle control with low incidence of irregular bleeding and altered withdrawal bleeding. The low incidence of gastrointestinal side effects (nausea, vomiting) may be related the low hormonal dose and to the vaginal delivery of hormones which avoids the gastrointestinal tract.