Corticotropin-releasing hormone and obesity: From fetal life to adulthood.

Obesity is among the most common chronic disorders, worldwide. It is a complex disease that reflects the interactions between environmental influences, multiple genetic allelic variants, and behavioral factors. Recent developments have also shown that biological conditions in utero play an important role in the programming of energy homeostasis systems and might have an impact on obesity and metabolic disease risk. The corticotropin-releasing hormone (CRH) family of neuropeptides, as a central element of energy homeostasis, has been evaluated for its role in the pathophysiology of obesity. This review aims to summarize the relevance and effects of the CRH family of peptides in the pathophysiology of obesity spanning from fetal life to adulthood.

Nanotechnology Applications in Sepsis: Essential Knowledge for Clinicians.

Sepsis is a life-threatening condition caused by a dysregulated host response to an invading pathogen such as multidrug-resistant bacteria. Despite recent advancements, sepsis is a leading cause of morbidity and mortality, resulting in a significant global impact and burden. This condition affects all age groups, with clinical outcomes mainly depending on a timely diagnosis and appropriate early therapeutic intervention. Because of the unique features of nanosized systems, there is a growing interest in developing and designing novel solutions. Nanoscale-engineered materials allow a targeted and controlled release of bioactive agents, resulting in improved efficacy with minimal side effects. Additionally, nanoparticle-based sensors provide a quicker and more reliable alternative to conventional diagnostic methods for identifying infection and organ dysfunction. Despite recent advancements, fundamental nanotechnology principles are often presented in technical formats that presuppose advanced chemistry, physics, and engineering knowledge. Consequently, clinicians may not grasp the underlying science, hindering interdisciplinary collaborations and successful translation from bench to bedside. In this review, we abridge some of the most recent and most promising nanotechnology-based solutions for sepsis diagnosis and management using an intelligible format to stimulate a seamless collaboration between engineers, scientists, and clinicians.

Heart Failure with Preserved Ejection Fraction: a Pharmacotherapeutic Update.

While guidelines for management of heart failure with reduced ejection fraction (HFrEF) are consensual and have led to improved survival, treatment options for heart failure with preserved ejection fraction (HFpEF) remain limited and aim primarily for symptom relief and improvement of quality of life. Due to the shortage of therapeutic options, several drugs have been investigated in multiple clinical trials. The majority of these trials have reported disappointing results and have suggested that HFpEF might not be as simply described by ejection fraction as previously though. In fact, HFpEF is a complex clinical syndrome with various comorbidities and overlapping distinct phenotypes that could benefit from personalized therapeutic approaches. This review summarizes the results from the most recent phase III clinical trials for HFpEF and the most promising drugs arising from phase II trials as well as the various challenges that are currently holding back the development of new pharmacotherapeutic options for these patients.

Urocortins as biomarkers in cardiovascular disease.

The urocortins (Ucns) belong to the corticotropin-releasing factor (CRF) family of peptides and have multiple effects within the central nervous and the cardiovascular systems. With growing evidence indicating significant cardioprotective properties and cardiovascular actions of these peptides, the question arises as to whether the plasma profiles of the Ucns are altered in pathologic settings. While reports have shown conflicting results and findings have not been corroborated in multiple independent cohorts, it seems likely that plasma Ucn concentrations are elevated in multiple cardiovascular conditions. The degree of increase and accurate determination of circulating values of the Ucns requires further validation.

The Use of Thalidomide in Severe Refractory Anaemia Due to Gastric Antral Vascular Ectasia (GAVE) in Cirrhosis?

Gastric antral vascular ectasia (GAVE) is a rare cause of upper gastrointestinal bleeding associated with cirrhosis. The first-line treatment is endoscopic therapy with argon plasma coagulation (APC). There is a high recurrence rate, but some evidence suggests that thalidomide could play an important role in controlling refractory anaemia due to GAVE. The authors present the case of a cirrhotic patient with a recent diagnosis of GAVE, who underwent multiple endoscopic treatments and blood transfusions because of haematemesis. The patient started thalidomide and 6 months later, there was no recurrence of haematemesis and haemoglobin levels were stable, with no reported adverse effects. LEARNING POINTS: The chronic bleeding associated with gastric antral vascular ectasia (GAVE) presenting with cirrhosis is more severe than that associated with portal hypertensive gastropathy.Argon plasma coagulation remains the first-line treatment, but GAVE has a high recurrence rate.Thalidomide could be an effective and safe option for recurrent bleeding due to GAVE in patients with cirrhosis.

Scalp cooling successfully prevents alopecia in breast cancer patients undergoing anthracycline/taxane-based chemotherapy.

INTRODUCTION: Chemotherapy for breast cancer induces alopecia, representing a major source of patient distress. This study assesses whether a scalp-cooling device is effective in reducing chemotherapy-induced alopecia, and assesses adverse treatment effects. MATERIALS AND METHODS: A prospective observational study including women with breast cancer undergoing chemotherapy and scalp cooling using a Paxman device. The primary efficacy end points were: successful hair preservation (no hair loss; <30% hair loss not requiring a wig; or <50% hair loss not requiring a wig) at the completion of chemotherapy. Secondary end points included adverse effects such as headache, pain, nausea or dizziness. RESULTS: The study enrolled 131 participants. Mean patient age was 49.8 years; 74% received anthracycline/taxane-based chemotherapy and 26% received taxane-monotherapy based chemotherapy. Hair preservation was successful in 102 women who underwent scalp cooling (71.0%; 95% CI = 63-79%). Only adverse events related to device use were collected, representing 7% (95% CI = 3-11%) of cases. CONCLUSIONS: Scalp cooling is effective in preventing hair loss among breast cancer patients undergoing standard chemotherapy treatment, and has minimal adverse effects.

The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features, nodal involvement, recurrence patterns and disease free survival.

AIMS: To evaluate how the St. Gallen intrinsic subtype classification for breast cancer surrogates predicts disease features, recurrence patterns and disease free survival. MATERIALS AND METHODS: Subtypes were classified by immunohistochemical staining according to St. Gallen subtypes classification in a 5-tyre system: luminal A, luminal B HER2-neu negative, luminal B HER2-neu positive, HER2-neu non luminal or basal-like. Data were obtained from the records of patients with invasive breast cancer treated at our institution. Recurrence data and site of first recurrence were recorded. The chi(2) test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between surrogates and clinicopathologic variables. RESULTS: A total of 2.984 tumors were classifiable into surrogate subtypes. Significant differences in age, tumor size, nodal involvement, nuclear grade, multicentric/multifocal disease (MF/MC), lymphovascular invasion, and extensive intraductal component (EIC) were observed among surrogates (p < 0.0001). After adjusting for confounding factors surrogates remained predictive of nodal involvement (luminal B HER2-neu pos. OR = 1.49 p = 0.009, non-luminal HER2-neu pos. OR = 1.61 p = 0.015 and basal-like OR = 0.60, p = 0.002) while HER2-neu positivity remained predictive of EIC (OR = 3.10, p < 0.0001) and MF/MC (OR = 1.45, p = 0.02). Recurrence rates differed among the surrogates and were time-dependent (p = 0.001) and site-specific (p < 0.0001). CONCLUSION: The St. Gallen 5-tyre surrogate classification for breast cancer subtypes accurately predicts breast cancer presenting features (with emphasis on prediction of nodal involvement), recurrence patterns and disease free survival.

Conservative surgery in ovarian borderline tumours: a meta-analysis with emphasis on recurrence risk.

BACKGROUND: Recent reports have stirred the debate regarding the optimal conservative treatment for both serous and mucinous borderline ovarian tumour (BOT). The aim of this study is to examine the optimal oncological approach of conservative surgery in unilateral BOT (cystectomy (C) versus unilateral salpingo-oophorectomy (USO)) and in bilateral BOT (bilateral C (BC) versus USO+contralateral C (CC)), as well as fertility outcomes. MATERIALS AND METHODS: The PubMed database and Cochrane Library were searched using the search terms (((Borderline) OR (low malignant potential)) AND (ovarian)) AND ((tumour) OR (cancer)) AND (((fertility sparing) OR (conservative)) AND surgery). RESULTS: We analysed 39 studies that included 5105 women (2624 patients with serous-, 2120 patients with mucinous- and the remaining with other types of BOT), 2752 of which underwent conservative surgery (817 underwent C, 89 BC, 1686 USO and 118 USO+CC). Eight studies included only stage I patients, in 14 studies more than 90% of patients were stage I and five studies included only late-stage patients. Seven studies included only patients with serous borderline ovarian tumour (sBOT) and two only mucinous borderline ovarian tumour (mBOT). A total of 296 patients with non-invasive-, 76 patients with invasive- and 50 patients with unspecified implants were pooled. Of the patients undergoing C, BC, USO and USO+CC the pooled recurrence estimates were respectively 25.3%, 25.6%, 12.5% and 26.1%. In meta-analysis, USO was significantly favored over C with an OR for recurrence reduction=2200, 95% CI=0.793-2.841 and p<0.0001. The pooled recurrence estimate as invasive ovarian cancer was 15.4% and the pooled 95% CI was 0.120-0.196. The cumulative pregnancy rate was 55.7% with 45.4% for USO and 40.3.0% for C. CONCLUSION: Cystectomy in unilateral serous BOT is significantly associated with a higher recurrence rate, albeit no impact on survival can be demonstrated. Whether this is related to the duration of follow-up, remains to be proven. Nonetheless, recent data seem to suggest that USO is advisable in the case of mucinous BOT. On the contrary, a more conservative approach (BC) should be definitively favored in bilateral BOT, which is almost always serous, because no significant difference is seen in terms of recurrence rate when compared to USO+CC.

A meta-analysis on the impact of platinum-based adjuvant treatment on the outcome of borderline ovarian tumors with invasive implants.

BACKGROUND: Treatment of borderline ovarian tumors (BOTs) remains contentious, and there is no consensus regarding therapy for BOTs with invasive implants (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in patients with BOTi at primary diagnosis. METHODS: The PubMed database was systematically searched for articles using the following terms: ((borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment) OR (surgery) OR (surgical treatment)). RESULTS: We identified 27 articles including 3,124 patients, 181 with invasive implants. All studies provided information regarding mortality or recurrence rates. Central pathological examination was performed in 19 studies. Eight studies included more than 75% stage I patients; 7 included only advanced-stage patients, and 14 included only serous BOT. The pooled recurrence estimates for both treatment groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ significantly (p = .114). A meta-analysis of the 6 studies providing separate mortality data for both treatment groups favored surgical treatment only, but this difference did not reach statistical significance (.05 < p < .1; odds ratio: 0.33; 95% confidence interval: 0.09-1.71; p = .086). We were unable to pool the results of the included studies because not all studies registered events in both treatment groups. Egger's regression indicated low asymmetry of the studies (p = .39), and no heterogeneity was found (I(2) = 0%). CONCLUSION: We did not find evidence supporting platinum-based adjuvant therapy for BOT with invasive implants.

Limited efficacy of platinum-based adjuvant treatment on the outcome of borderline ovarian tumors.

Adjuvant treatment of borderline ovarian tumors (BOT) remains highly debatable. This article evaluates the benefits of platinum-based adjuvant treatment in patients with BOT. The PubMed and Cochrane Library databases were systematically searched for articles using the terms ((Borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment)). We identified 31 articles including 4965 patients. Together, 592 patients presented non-invasive-, 244 invasive- and 77 unspecified implants. Central pathological examination was performed in 23 studies. Nine studies included more than 90% stage I patients, while 11 included only advanced stage patients. Nineteen studies reported patients undergoing complete cytoreduction, ten reported response rates and eight compared survival outcomes. All studies provided information regarding either mortality or recurrence rates. A meta-analysis of the 13 studies providing separate mortality data for both treatment groups, including 2206 women, favored surgical treatment only (OR=7.44; 95% CI=3.39-16.32; p<0.0005) albeit with moderate heterogeneity of the studies (I(2)=35.0%) but no asymmetry (Egger's test p=0.44). Regarding survival data, 4 studies reported no difference between groups. In the adjuvant setting, 4 reported worse outcome and 1 reported a nonsignificant trend to worse outcome. At present, there is no evidence to support the use of adjuvant treatment in patients with BOT.

Massive breast necrosis after extravasation of a full anthracycline cycle.

A 57-year-old woman with invasive breast cancer was referred for adjuvant chemotherapy after undergoing breast conservative therapy and axillary dissection. A port was inserted in the contralateral subclavian vein and epirubicin, cyclophosphamide and 5-fluorouracil was the treatment of choice. After the first cycle, the patient was sent home. The following day, she reported rapidly developing redness and pain in the right breast and diagnosis of epirubicin extravasation was made. She was hospitalised, the port was surgically removed and approximately two-thirds of the breast underwent tissue necrosis. The necrotic tissue was resected and a skin graft was harvested from the thigh. She was offered DIEP-flap reconstruction 8 months later. There were no complications, except for marginal necrosis of the flap. Necrosectomy was performed and resolved through an advancement flap.

The cellular ratio of immune tolerance (immunoCRIT) is a definite marker for aggressiveness of solid tumors and may explain tumor dissemination patterns.

The adaptive immune system is involved in tumor establishment and aggressiveness. Tumors of the ovaries, an immune-privileged organ, spread via transceolomic routes and rarely to distant organs. This is contrary to tumors of non-immune privileged organs, which often disseminate hematogenously to distant organs. Epigenetics-based immune cell quantification allows direct comparison of the immune status in benign and malignant tissues and in blood. Here, we introduce the "cellular ratio of immune tolerance" (immunoCRIT) as defined by the ratio of regulatory T cells to total T lymphocytes. The immunoCRIT was analyzed on 273 benign tissue samples of colorectal, bronchial, renal and ovarian origin as well as in 808 samples from primary colorectal, bronchial, mammary and ovarian cancers. ImmunoCRIT is strongly increased in all cancerous tissues and gradually augmented strictly dependent on tumor aggressiveness. In peripheral blood of ovarian cancer patients, immunoCRIT incrementally increases from primary diagnosis to disease recurrence, at which distant metastases frequently occur. We postulate that non-pathological immunoCRIT values observed in peripheral blood of immune privileged ovarian tumor patients are sufficient to prevent hematogenous spread at primary diagnosis. Contrarily, non-immune privileged tumors establish high immunoCRIT in an immunological environment equivalent to the bloodstream and thus spread hematogenously to distant organs. In summary, our data suggest that the immunoCRIT is a powerful marker for tumor aggressiveness and disease dissemination.