The Molecular Mechanisms Underlying the Systemic Effects Mediated by Parathormone in the Context of Chronic Kidney Disease.

Chronic kidney disease (CKD) stands as a prominent non-communicable ailment, significantly impacting life expectancy. Physiopathology stands mainly upon the triangle represented by parathormone-Vitamin D-Fibroblast Growth Factor-23. Parathormone (PTH), the key hormone in mineral homeostasis, is one of the less easily modifiable parameters in CKD; however, it stands as a significant marker for assessing the risk of complications. The updated "trade-off hypothesis" reveals that levels of PTH spike out of the normal range as early as stage G2 CKD, advancing it as a possible determinant of systemic damage. The present review aims to review the effects exhibited by PTH on several organs while linking the molecular mechanisms to the observed actions in the context of CKD. From a diagnostic perspective, PTH is the most reliable and accessible biochemical marker in CKD, but its trend bears a higher significance on a patient's prognosis rather than the absolute value. Classically, PTH acts in a dichotomous manner on bone tissue, maintaining a balance between formation and resorption. Under the uremic conditions of advanced CKD, the altered intestinal microbiota majorly tips the balance towards bone lysis. Probiotic treatment has proven reliable in animal models, but in humans, data are limited. Regarding bone status, persistently high levels of PTH determine a reduction in mineral density and a concurrent increase in fracture risk. Pharmacological manipulation of serum PTH requires appropriate patient selection and monitoring since dangerously low levels of PTH may completely inhibit bone turnover. Moreover, the altered mineral balance extends to the cardiovascular system, promoting vascular calcifications. Lastly, the involvement of PTH in the Renin-Angiotensin-Aldosterone axis highlights the importance of opting for the appropriate pharmacological agent should hypertension develop.

Biomarkers Involved in the Pathogenesis of Hemophilic Arthropathy.

Hemophilia, which is a rare disease, results from congenital deficiencies of coagulation factors VIII and IX, respectively, leading to spontaneous bleeding into joints, resulting in hemophilic arthropathy (HA). HA involves complex processes, including synovial proliferation, angiogenesis, and tissue remodeling. Despite ongoing research, factors contributing to HA progression, especially in adults with severe HA experiencing joint pain, remain unclear. Blood markers, particularly collagen-related ones, have been explored to assess joint health in hemophilia. For example, markers like CTX-I and CTX-II reflect bone and cartilage turnover, respectively. Studies indicate elevated levels of certain markers post-bleeding episodes, suggesting joint health changes. However, longitudinal studies on collagen turnover and basement membrane or endothelial cell markers in relation to joint outcomes, particularly during painful episodes, are scarce. Given the role of the CX3CL1/CX3XR1 axis in arthritis, other studies investigate its involvement in HA. The importance of different inflammatory and bone damage biomarkers should be assessed, alongside articular cartilage and synovial membrane morphology, aiming to enhance understanding of hemophilic arthropathy progression.

Debates Surrounding the Use of Antithrombotic Therapy in Hemophilic Patients with Cardiovascular Disease: Best Strategies to Minimize Severe Bleeding Risk.

Navigating through antithrombotic therapy in patients with both hemophilia and cardiovascular pathology presents a complex scenario with inherent challenges and opportunities. The presence of hemophilia, characterized by impaired blood clotting, adds a layer of complexity to the management of cardiovascular conditions requiring antiplatelet therapy and anticoagulation. Striking a delicate balance between the necessity for antithrombotic treatment to prevent cardiovascular events and the heightened risk of severe bleeding in individuals with hemophilia demands a nuanced and carefully considered approach. The challenges revolve around identifying an optimal therapeutic strategy that effectively mitigates cardiovascular risks without exacerbating bleeding tendencies. In hemophilic patients with cardiovascular disease, the decision to use antiplatelet therapy requires careful consideration of the individual's bleeding risk profile, considering factors such as the severity of hemophilia, history of bleeding episodes, and concurrent medications. The goal is to provide effective antithrombotic treatment while minimizing the potential for excessive bleeding complications. Conventional anticoagulants like warfarin pose difficulties due to their potential to increase the risk of bleeding. On the other hand, emerging options like novel direct oral anticoagulants (DOACs) present an opportunity, offering predictable pharmacokinetics and user-friendly administration. However, a comprehensive exploration of their safety and efficacy in hemophilic patients is imperative. Achieving the right equilibrium between preventing cardiovascular events and minimizing bleeding risk is pivotal in selecting the most effective therapeutic option for individuals with hemophilia and cardiovascular pathology. A multidisciplinary approach, integrating the expertise of hematologists and cardiologists, becomes essential to customize treatments and address the intricacies of this medical challenge.

Oncolytic Virotherapy: A New Paradigm in Cancer Immunotherapy.

Oncolytic viruses (OVs) are emerging as potential treatment options for cancer. Natural and genetically engineered viruses exhibit various antitumor mechanisms. OVs act by direct cytolysis, the potentiation of the immune system through antigen release, and the activation of inflammatory responses or indirectly by interference with different types of elements in the tumor microenvironment, modification of energy metabolism in tumor cells, and antiangiogenic action. The action of OVs is pleiotropic, and they show varied interactions with the host and tumor cells. An important impediment in oncolytic virotherapy is the journey of the virus into the tumor cells and the possibility of its binding to different biological and nonbiological vectors. OVs have been demonstrated to eliminate cancer cells that are resistant to standard treatments in many clinical trials for various cancers (melanoma, lung, and hepatic); however, there are several elements of resistance to the action of viruses per se. Therefore, it is necessary to evaluate the combination of OVs with other standard treatment modalities, such as chemotherapy, immunotherapy, targeted therapies, and cellular therapies, to increase the response rate. This review provides a comprehensive update on OVs, their use in oncolytic virotherapy, and the future prospects of this therapy alongside the standard therapies currently used in cancer treatment.

Predicting the Feasibility of Curative Resection in Low Rectal Cancer: Insights from a Prospective Observational Study on Preoperative Magnetic Resonance Imaging Accuracy.

Background and Objectives: A positive pathological circumferential resection margin is a key prognostic factor in rectal cancer surgery. The point of this prospective study was to see how well different MRI parameters could predict a positive pathological circumferential resection margin (pCRM) in people who had been diagnosed with rectal adenocarcinoma, either on their own or when used together. Materials and Methods: Between November 2019 and February 2023, a total of 112 patients were enrolled in this prospective study and followed up for a 36-month period. MRI predictors such as circumferential resection margin (mCRM), presence of extramural venous invasion (mrEMVI), tumor location, and the distance between the tumor and anal verge, taken individually or combined, were evaluated with univariate and sensitivity analyses. Survival estimates in relation to a pCRM status were also determined using Kaplan-Meier analysis. Results: When individually evaluated, the best MRI predictor for the detection of a pCRM in the postsurgical histopathological examination is mrEMVI, which achieved a sensitivity (Se) of 77.78%, a specificity (Sp) of 87.38%, a negative predictive value (NPV) of 97.83%, and an accuracy of 86.61%. Also, the best predictive performance was achieved by a model that comprised all MRI predictors (mCRM+ mrEMVI+ anterior location+ < 4 cm from the anal verge), with an Se of 66.67%, an Sp of 88.46%, an NPV of 96.84%, and an accuracy of 86.73%. The survival rates were significantly higher in the pCRM-negative group (p < 0.001). Conclusions: The use of selective individual imaging predictors or combined models could be useful for the prediction of positive pCRM and risk stratification for local recurrence or distant metastasis.

Robotic-Assisted Pelvic Surgery: Early Outcomes in a Single Institution.

Introduction: This article reports the authors' experience with their first 50 consecutive robotic pelvic procedures, aiming to determine the feasibility and safety of adopting robotic pelvic surgery. Robotic surgery offers several benefits for minimally invasive surgery, but its applicability is hindered by cost and limited regional experience. This study aimed to evaluate the feasibility and safety of robotic pelvic surgery. Material and Methods: This is a retrospective review of our initial experience with robotic surgery for colorectal, prostate, and gynaecologic neoplasia, between June and December 2022. The surgical outcomes were evaluated in terms of perioperative data, such as operative time, estimated blood loss, and length of hospital stay. Intraoperative complications were recorded, and postoperative complications were evaluated at 30 days and 60 days after surgery. The feasibility of the roboticassisted surgery was assessed by measuring the conversion rate to laparotomy. The safety of the surgery was evaluated by recording the incidence of intraoperative and postoperative complications. Results: Fifty robotic surgeries were performed over 6 months, including 21 interventions for digestive neoplasia, 14 gynaecologic cases, and 15 prostatic cancers. Operative time ranged from 90 to 420 minutes, with two minor complications and two grade II Clavien-Dindo complications. One patient required prolonged hospitalization and an end-colostomy, deriving from an anastomotic leakage requiring reintervention. No thirty-day mortality or readmissions were reported. Conclusion: The study found that robotic-assisted pelvic surgery is safe and has a low rate of transfer to open surgery, making it a suitable addition to conventional laparoscopy.

The Usefulness of Assessing Heart Rate Variability in Patients with Acute Myocardial Infarction (HeaRt-V-AMI).

BACKGROUND: Heart rate variability (HRV) could have independent and critical prognostic values in patients admitted for ST segment elevation myocardial infarction (STEMI). There are limited data in the literature regarding HRV assessment in STEMI setting. Thus, we aim to investigate the potential correlations between HRV and adverse outcomes in a contemporary cohort of patients presenting with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: We will perform a prospective, observational cohort study in a single healthcare center. Adult patients aged ≥18 years presenting with STEMI in sinus rhythm will be enrolled for primary PCI within 12 h from symptoms onset. Time domain, frequency domain, and nonlinear HRV parameters will be measured using a medically approved wrist-wearable device for 5 min segments during myocardial revascularization by primary PCI. Additional HRV measurements will be performed one and six months from the index event. The primary composite outcome will include all-cause mortality and major adverse cardiovascular events (during the hospital stay, one month, and one year following admission). Several secondary outcomes will be analyzed: individual components of the primary composite outcome, target lesion revascularization, hospitalizations for heart failure, ventricular arrhythmias, left ventricular ejection fraction, and left ventricular diastolic function. CONCLUSIONS: Our study will enlighten the reliability and usefulness of HRV evaluation as a prognostic marker in contemporary patients with STEMI. The potential validation of HRV as a risk marker for adverse outcomes following STEMI will ensure a background for including HRV parameters in future risk scores and guidelines.

Outcomes Following Surgery for Locally Advanced Pancreatic Cancer - Single Center Experience. A Retrospective Study.

Background: Pancreatic cancer represents one of the most frequent cancers with an increased incidence. Most cases on initial diagnosis are considered to be locally advanced and surgery remains the most important therapeutic option. The aim of this study was to evaluate postoperative morbidity that can impair the association of adjuvant therapy. Methods: We performed a retrospective study on a prospective database that includes all the patients diagnosed with pancreatic cancer in which surgery was performed between 2012 and 2021. We divided the patients in advanced tumours and localized tumours and we compared the outcomes after surgery. Results: On 58 patients with pancreatic tumours surgery was performed: 28(48.3%) pancreaticoduodenectomies and 30 (51.7%) distal pancreatectomies. Localized tumours (T1 and T2) were encountered in 32 patients (55.2%) and more advanced tumours (T3 and T4) were present in 26 cases (44.8%). Although there was no significant difference either for major complications, we observed a tendency for patients with advanced tumours to develop a major complication (15.6% vs 34.6%, p=0.09). The occurrence of major complication, such as pancreatic fistula and postoperative hemorrhage, there was no significant difference (6.25% vs 7.69% and 6.25% vs. 23.1%). On multivariate analysis of preoperative factors associated with the occurrence of a severe complication only the CA19-9 levels were associated with an increased risk (odds ratio 0.666, 95% CI 0.5-1.01; p= 0.04) Conclusions: This study showed no significant differences in terms of postoperative complications between the two subgroups. CA 19-9 is an accurate biomarker for the prediction of postoperative complications.

Evaluation of Immediate Inflammatory Response in Thoracoscopic Esophageal Resection versus Open Approach - A Prospective Study.

Introduction: There is an immune response after major surgery and inflammatory complications following complex surgery have a direct impact on morbidity and mortality. Currently, we do not have clinical tools to predict in which subset of patients a major complication will occur. The aim of this study was to evaluate the immediate dynamics of C-reactive protein (CRP), presepsin and procalcitonin in patients in which esophagectomy was performed either through video assisted thoracic surgery (VATS) or open approach. Methods: We conducted a prospective study on 27 patients with a mean age of 61.48 +-6.80 years, 13 patients with VATS and 14 with open approach, most of the patients were on stage III esophageal cancer (81%) and in all cases neoadjuvant treatment was performed. Results: There were increased levels of CRP, presepsin and procalcitonin after both arms of the study with significantly higher values for the open approach and with the same dynamic curves. In 3 cases there were extremely elevated levels of procalcitonin in the absence of a septic complication, in all cases a major complication occurred. Conclusion: Video assisted thoracoscopic esophageal mobilization induces a less immune response, even with the association of laparotomy. An elevated postoperative procalcitonin level can be an early indicator of a major postoperative complication.

"Liquid Biopsy" - Is it a Feasible Option in Colorectal Cancer?

It is important for surgeons to keep up with improvements both in and outside their field. As medicine evolves, new techniques appear, and oncology is one of the main beneficiaries. "Liquid biopsy" is one of the most recent domains of interest in oncology, as it may provide important details regarding the characteristics of the main tumor and its metastases. Malignant cells are in a continuous dynamic, which makes the initial diagnostic biopsy and the pathological specimen evaluation insufficient in the late evolution of the disease, when relapse or metastases may appear. The fact that the healthcare provider is able to find out additional information about the tumor at a given time, by evaluating a blood sample to obtain a "liquid biopsy" is of utmost importance and gives multiple potentially usable data. There are three means of obtaining biological material that may be used as "liquid biopsy": evaluation of circulating tumor cells, circulating tumor DNA and exosomes. The most intensely studied entity is that of circulating tumor cells, with different applications, amongst which the most important, at present time, is the prognostic value that has important demonstrated implications, not only in breast and prostate cancer, but also in colorectal cancer. Although surgery will, most certainly, not be replaced by other treatments when aiming for a curative approach to rectal cancer, it is important for the surgeon to know information about complementary fields, one of which is comprised by "liquid biopsy".

The Influence of Neoadjuvant Treatment on the Number of Lymph Nodes on the Surgical Specimen in Mid and Low Rectal Cancer - A Retrospective Single-Centre Study.

Introduction: In this study, we aim to identify the impact of neoadjuvant radiation treatment upon the number of harvested and positive lymph nodes in the surgical specimen; in addition, we tried to identify the impact of chemotherapy in association with radiotherapy on said structures. Patients and methods: In the study we included patients treated for rectal cancer within a single oncologic surgical Unit serving the north-eastern part of Romania, over a period of 5 and a half years, between May 2013 and April 2018. Firstly, we compared pathologic lymph node status to pretherapeutic staging. Secondly, we compared lymph node values in relation to the treatment scheme. Results: There was a total of 498 patients treated radically through open surgery for low and mid rectal cancer. We saw a decrease in N staging in 218 cases, 65 remaining stationary and 10 increasing their lymph node staging on the surgical specimen. We identified significant differences between the total number of lymph nodes (17.4 vs 24.2, p 0.001), the number of positive lymph nodes (1.4 vs 3.4, p 0.001) and the ratio between positive and total lymph nodes (0.08 vs 0.14, p 0.001) in patients with and without neoadjuvant treatment respectively. However, there was no statistical difference between patients with and without chemotherapy associated to radiotherapy in the neoadjuvant treatment plan (p=0.539, p=0.58, p=0.575). Conclusion: This study shows there are significant variations according to the application of neoadjuvant treatment, between the numbers of positive and total lymph nodes, as well as the positive/total lymph node ratio.

Hindgut and Midgut Neuroendocrine Tumors - Therapeutic Approach.

Introduction: Neuroendocrine tumors of the gastro-entero-pancreatic system have a variety of components, clinical manifestations and prognostic indices according to their anatomical site. Therefore, their diagnostic and management strategies differ a great deal. Prognosis concerning NETs can be poor due to the degree of differentiation, early metastasizing and the high degree of invasiveness. Material and Methods: For the present study, the patient files were evaluated and the parameters of interest were followed. Results: Over the course of 6 years there were 37 patients diagnosed with and treated for NETs, regardless of primary tumor site. There were 9 patients with NETs of the primite mid- and hindgut thusly: 5 cases with colorectal NETs and 4 cases of small bowel NETs. 6 patients benefited from radical surgical treatment, 2 cases with palliative procedures and only one patient with tumor biopsy. The tumors were evaluated according to the 2010 WHO classification based on the number of mitoses and the Ki67 proliferation index. Adjuvant treatment was adapted according to staging and histopathological parameters. Conclusions: Despite recent progress in managing NETs, there are still many controversial aspects regarding the management of these cases, mainly about timing the right sequence of therapy.

Management of Gastric Stromal Tumour - Multicenter Observational Study.

Background: Gastrointestinal stromal tumors are some of the most common mesenchymal tumors of the gut. The aim of this study is to asses the clinical manifestation and treatment of gastric GISTs. Methodology: We performed a retrospective 5-year multicenter study conducted on a prospective collected database, which includes all the patients diagnosed with GIST in which surgery was performed. We selected all the pateients with gastric GISTs and we analyzed the clinical manifestation, treatment and prognostic factors. Results: There were 42 patients with GISTs of which the gastric GISTs were encountered in 23 cases (54.76%). There were 7 laparoscopic resections and 16 open surgery resections. Pathological examination showed that many of the patients were in group 6a and 6b (30.43%). CD117 was positive in 91.3% of cases. Regarding postoperative morbidity, there were 4 cases of pulmonary complications, 3 cases of surgical site infection and one postoperative hemorrhage. Conclusions: In our experience surgery for gastric GIST must be performed by a highly trained team, the keyset for a improved survival is the multidisciplinary approach that includes an accurate diagnosis, prognostic risk stratification and accurate treatment.

Impact of Surgery and Early Postoperative Outcomes After Radical Gastrectomy for Cancer.

Background: Surgery remains one of the most important part of the multimodal treatment of patients diagnosed with gastric cancer. Due to the fact that the consequences in terms of postoperative morbidity can delay the onset of postoperative chemotherapy or even can make the patient unfitted for adjuvant treatment, a thorough clinical evaluation of patient prior to surgery is mandatory. Methods: We performed a retrospective study, which included all the patients diagnosed with gastric cancer in which radical surgery was performed during a 5-year period in a single center. All the patients, tumour and surgery characteristics were used for a risk analysis for the occurrence of overall, medical and surgical complications. Results: There were 189 patients in whom radical surgery was performed, 100 (52.9%) total gastrectomies and 89 (47.1%) subtotal gastrectomies, without difference in term of postoperative morbidity. There were 25 (13.2%) cases of duodenal stump fistula, 15 (15%) cases of esojejunal fistula. On multivariate analysis albumin levels (OR 1.9, p=0.035), hypertension (OR 4.22, p=0.0311) and splenectomy (OR 3.91, p=0.048) were independent factors for overall complications, albumin levels (OR 1.91, p=0.0405), hypertension (OR 3.54, p=0.0444), neoadjuvant treatment (OR 3.97, p=0.01657) and splenectomy (Or 1.66 p=0.05) for medical complications; age (OR 1.71,p=0.044), hypertension (OR 2.22, p=0.045) and albumin levels (OR 1.92, p=0.041) for surgical type complications. Conclusions: Postoperative morbidity after gastrectomy remains one of the most important factors that can impair the effectuation of a multimodal treatment protocol. Comorbidity factors, nutritional status and surgical technique are the key factors that can influence the amount and the consequence of a surgical complication.

Functional Results Following Pylorus-Preserving Pancreatoduodenectomy with Pancreaticogastrostomy.

Background: Pylorus preserving (PP) pancreaticoduodenectomy (PD) has several advantages in terms of shorter operation time and improved nutritional status but with an increased risk for delayed gastric emptying. Methods: We performed a retrospective study on all patients in which PD was performed from May 2012 to May 2018. It was analyzed early postoperative outcomes and the incidence of delayed gastric emptying (DGE) syndrome for patients with pylorus PP PD technique and pancreaticogastrostomy (PG). Results: There were 47 PD, in which PP technique was performed in 42 cases. The tumour location was in the pancreatic head (n=21, 44.68%), periampullary (ampulla of Vater) (n=14,29.78%), distal bile duct (n=7,14.89%), duodenum (n=2, 4.25%) and advanced right colon cancer (n=3, 6.38%). There were 10 cases (21.2%) of grade III-V complications, grade A pancreatic fistula (PF)8 cases (17%), grade B in 3 cases (6.4%) and grade C in 1 case (2.12%). DGE was encountered in 17 cases (36.17%), grade A 2 cases (4.25%), grade B in 4 cases (8.5%) and grade C in 2 cases (4.25%). Biliary fistula occurred in 3 cases (6.4%) and in 4 cases relaparotomy was needed. Conclusions: The results of our study are concluding with the previous studies, the addition of PG to PP PD does not increase the risk of DGE.

[Focus on the Immunoscore and its potential clinical implications]. / Mise au point sur l'Immunoscore et ses potentielles implications cliniques.

The role of the immune response at the tumor site is now recognized as crucial in the clinical course of patients with cancer. The importance of the immune cell type, their functional orientation, their density and location within the tumor's regions (tumor/invasion margin) has recently been shown and were grouped together under the term "immune contexture". A strong infiltration by cytotoxic and memory T cells in a Th1-polarized tumor microenvironment appears to have a major prognosis impact. A test called Immunoscore taking into account these various parameters has been suggested to measure in a simple, reproducible and robust manner the intra- and peritumoral immune response. The prognostic value of Immunoscore has recently been validated in colon cancers by a large international retrospective study under the aegis of the Society for Immunotherapy of Cancer (SITC). The Immunoscore could have several potential clinical applications such as prognostic as well as theranostic.

Tricuspid Regurgitation Associated with Implantable Cardiac Devices: A Double-Edged Sword.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; the prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, the management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlights the clinical importance, underlying mechanisms and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

Heart Rate Variability in Acute Myocardial Infarction: Results of the HeaRt-V-AMI Single-Center Cohort Study.

(1) Background: Heart rate variability (HRV) has been investigated in the context of ST-segment elevation myocardial infarction (STEMI). This study contributes to the field by assessing short-term HRV during primary percutaneous coronary intervention (PCI) using wearable technology, providing real-time insights into autonomic function. (2) Methods: This single-center, observational cohort study included 104 STEMI patients undergoing primary percutaneous coronary intervention (PCI). HRV parameters (including SDNN, RMSSD, pNN50, HF, SD1, and SD2/SD1 ratio) were measured using a wearable device (Empatica E4 wristband, CE certified). Measurements were taken throughout the entire duration of the primary PCI, as well as specifically during the initial 5 min and the final 5 min of the procedure. The association between HRV parameters and adverse outcomes, including in-hospital mortality and in-hospital major adverse cardiovascular events (MACE), were assessed. (3) Results: HRV parameters significantly decreased after myocardial revascularization, particularly SDNN, RMSSD, pNN50, HF, SD1, and SD2/SD1 ratio. Significant associations were found between reduced SD2/SD1 ratio, approximate entropy, and adverse outcomes, including increased in-hospital mortality and in-hospital MACE (respectively, p = 0.007, p = 0.017 and p = 0.006 and p = 0.005). The SD2/SD1 ratio was significantly lower in patients who died during the hospital stay (p = 0.008) compared to survivors. Approximate entropy was also significantly lower in deceased patients (p = 0.019). (4) Conclusions: Real-time HRV monitoring using wearable technology offers valuable data regarding dynamic physiological changes during primary PCI. Further studies are required to validate these preliminary results and to explore their potential implications for clinical practice.

The Link between Obesity and Gastrointestinal Cancers: a Short Review.

Gastrointestinal cancer represents one of the most encountered oncologic pathologies and research studies are performed thoroughly in order to identify the exact causes and possible novel therapies. Obesity is a complex manifestation associated with numerous physiological and primarily molecular changes capable of tackling the behavior of tumoral cells and the nearby or faraway microenvironment. Adipose tissue has been once considered to have limited physiological roles, but in recent years it has been recognized as an active endocrine organ, secreting substances such as growth factors and adipokines. From an epidemiological perspective, obesity - particularly morbid obesity - is linked to an unfavorable progression of cancer. A key mechanism that may elucidate the association between obesity and cancer involves the insulin and insulin-like growth factor (IGF-1) pathway, sex hormones, and adipokines.

The association between klotho and kidney and cardiovascular outcomes: a comprehensive systematic review and meta-analysis.

Background: Chronic kidney disease (CKD) and end-stage renal disease (ESKD) are significant global health challenges associated with progressive kidney dysfunction and numerous complications, including cardiovascular disease and mortality. This study aims to explore the potential association between plasma klotho levels and various prognostic outcomes in CKD and ESKD, including all-cause mortality, cardiovascular events, metabolic syndrome development and adverse renal events necessitating renal replacement therapies. Methods: A literature search was conducted through 3 June 2024 using the electronic databases Cochrane Library, Ovid MEDLINE, CINAHL, Web of Science, SCOPUS and PubMed. This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Fourteen studies were included. For all-cause mortality, comparing CKD patients with low versus high klotho levels showed a significant association {odds ratio [OR] 1.81 [95% confidence interval (CI) 1.34-2.44], P = .0001}, with substantial heterogeneity (I 2 = 69%). Excluding one study reduced heterogeneity (I 2 = 43%) while maintaining significance [OR 1.97 (95% CI 1.45-2.66), P < .0001]. Cardiovascular mortality was higher in patients with low klotho levels [OR 2.11 (95% CI 1.61-2.76), P < .00001], with low heterogeneity (I 2 = 25%). Excluding one study eliminated heterogeneity (I 2 = 0%) while maintaining significance [OR 2.39 (95% CI 1.83-3.12), P < .00001]. Composite cardiovascular events did not differ significantly between low and high klotho groups [OR 1.51 (95% CI 0.82-2.77), P = .18], but with high heterogeneity (I 2 = 72%). Patients with low klotho levels had a higher risk of adverse renal events [OR 2.36 (95% CI 1.37-4.08), P = .002], with moderate heterogeneity (I 2 = 61%). Sensitivity analysis reduced heterogeneity (I 2 = 0%) while maintaining significance [OR 3.08 (95% CI 1.96-4.85), P < .00001]. Specifically, for ESKD or kidney replacement therapy risk, low klotho levels were associated with an increased risk [OR 2.30 (95% CI 1.26-4.21), P = .007]. Similarly, CKD progression risk was higher in patients with lower klotho levels [OR 2.48 (95% CI 1.45-4.23), P = .0009]. Conclusion: Lower serum klotho levels serve as a significant predictor of adverse outcomes, including increased risks of all-cause mortality, cardiovascular mortality and progression to end-stage kidney disease among CKD patients.