The tumor microenvironment (TME) is a complex and ever-changing “rogue organ” composed of its own blood supply, lymphatic and nervous systems, stroma, immune cells and extracellular matrix (ECM). These complex components, utilizing both benign and malignant cells, nurture the harsh, immunosuppressive and nutrient-deficient environment necessary for tumor cell growth, proliferation and phenotypic flexibility and variation. An important aspect of the TME is cellular crosstalk and cell-to-ECM communication. This interaction induces the release of soluble factors responsible for immune evasion and ECM remodeling, which further contribute to therapy resistance. Other aspects are the presence of exosomes contributed by both malignant and benign cells, circulating deregulated microRNAs and TME-specific metabolic patterns which further potentiate the progression and/or resistance to therapy. In addition to biochemical signaling, specific TME characteristics such as the hypoxic environment, metabolic derangements, and abnormal mechanical forces have been implicated in the development of treatment resistance. In this review, we will provide an overview of tumor microenvironmental composition, structure, and features that influence immune suppression and contribute to treatment resistance.

The incidence of both diabetes mellitus type 2 and heart failure is rapidly growing, and the diseases often coexist. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new antidiabetic drug class that mediates epithelial glucose transport at the renal proximal tubules, inhibiting glucose absorption—resulting in glycosuria—and therefore improving glycemic control. Recent trials have proven that SGLT2i also improve cardiovascular and renal outcomes, including reduced cardiovascular mortality and fewer hospitalizations for heart failure. Reduced preload and afterload, improved vascular function, and changes in tissue sodium and calcium handling may also play a role. The expected paradigm shift in treatment strategies was reflected in the most recent 2021 guidelines published by the European Society of Cardiology, recommending dapagliflozin and empagliflozin as first-line treatment for heart failure patients with reduced ejection fraction. Moreover, the recent results of the EMPEROR-Preserved trial regarding empagliflozin give us hope that there is finally an effective treatment for patients with heart failure with preserved ejection fraction. This review aims to assess the efficacy and safety of these new anti-glycemic oral agents in the management of diabetic and heart failure patients.

Patient survival continues to increase with the growing quality of dialysis and management of chronic kidney disease (CKD). As such, chronic therapy must include considerations of quality of life (QOL), and this includes the disproportionate prevalence of sexual dysfunction (SD) in this patient population. This review aims to describe the pathophysiological and the psychosocial causes of SD with regard to renal replacement therapy, particularly hemo- and peritoneal dialysis. The differences in its manifestation in men and women are compared, including hormonal imbalances—and therefore fertility, libido, and sexual satisfaction—the experience of depression and anxiety, and QOL. The impact of comorbidities and the iatrogenic causes of SD are described. This review also presents validated scales for screening and diagnosis of SD in CKD patients and outlines novel therapies and strategies for the effective management of SD. Increased prevalence of CKD invariably increases the number of patients with SD, and it is crucial for health care professional teams to become familiar with the clinical tools used to manage this sensitive and under-quantified field. As a known predictor of QOL, sexual function should become a point of focus in the pursuit of patient-centered care, particularly as we seek to achieve as “normal” a life as possible for individuals who receive dialysis.

Background: The population of end-stage renal disease (ESRD) patients with diabetes mellitus (DM) may be at increased risk of protein energy wasting (PEW). The aim of the study was to investigate the impact of DM on selected indicators of PEW in the ESRD population that was undergoing maintenance hemodialysis (MHD). Methods: A total of 515 MHD patients were divided into two subgroups with and without DM. The evaluation of diet composition, Charlson Comorbidity Index (CCI), SGA, and laboratory and BIS analyses were performed. All-cause and cardiovascular mortality was recorded. Results: DM patients had lower albumin (3.93 (3.61–4.20) vs. 4.10 (3.80–4.30) g/dL, p < 0.01), total cholesterol (158 (133–196) vs. 180 (148–206) mg/dL, p < 0.01), and creatinine (6.34 (5.08–7.33) vs. 7.12 (5.70–8.51) mg/dL, p < 0.05). SGA score (12.0 (10.0–15.0) vs. 11.0 (9.0–13.0) points, p < 0.001), BMI (27.9 (24.4–31.8) vs. 25.6 (22.9–28.8) kg/m², p < 0.001), fat tissue index (15.0 (11.4–19.6) vs. 12.8 (9.6–16.0) %, p < 0.001), and overhydration (2.1 (1.2–4.1) vs. 1.8 (0.7, 2.7) L, p < 0.001) were higher in the DM group. Increased morbidity, reflected in the CCI and mortality—both all-cause and cardiovascular—were observed in DM patients. Conclusions: Hemodialysis recipients with DM experience overnutrition with a paradoxically higher predisposition to PEW, expressed by a higher SGA score and lower serum markers of nutrition. This population is also more comorbid and is at higher risk of death, including from cardiovascular causes.

Background Surgery, the treatment of choice for parotid pleomorphic adenoma (PA), is associated with facial nerve palsy and decreased quality of life. Re-operation for PA recurrence (rPA) significantly increases these risks and constitutes a dilemma for both patient and surgeon. Factors influencing the success of re-operation, as well as the self-reported satisfaction of both sides, have yet to be addressed in the literature. This study aims to improve upon the decision-making schedule in PA re-operations, based on patient expectations, imaging, and concordance with the first operative report (FOpR). Methods Seventy-two rPAs treated in a single tertiary center were collected and analyzed. The FOpRs and pre-operative imaging were divided according to defined criteria into accurate and non-accurate categories. The re-operative field and course were categorized as anticipated or unanticipated. The re-operation was categorized as satisfactory or unsatisfactory for both the patient and the surgeon. Results The accuracy of FOpRs and pre-operative imaging was 36.1% and 69.4%, respectively. Re-operative courses were: 36.1% anticipated and 63.9% unanticipated. The most frequently omitted data were: presence of satellite tumors (9.7%), and amount of removed parenchyma (9.7%). Variables that most commonly affected FOpR non-accuracy were: tumor size (Chi2(1)=59.92; p < 0.001) and capsule condition (Chi2(1)=29.11; p < 0.001). There was no significant relationship between FOpR accuracy and re-operative course (Chi2(1)=1.14; p = 0.286), patient satisfaction (Chi2(1)=1.94; p = 0.164) or surgeon satisfaction (Chi2(1)=0.04; p = 0.837). Pre-operative imaging (Chi2(1)=36.73; p < 0.001) had the greatest impact on surgeon satisfaction. Conclusion Accurate pre-operative imaging impacted surgeon satisfaction. The impact of the FOpR on re-operation technicalities and patient satisfaction was minor. Imaging precision should be improved to streamline the decision-making process of PA re-operation. This article proposes suggestions for a future decision-making algorithm as a starting point for a prospective study. Key messages Accurate pre-operative imaging impacts both surgeon and patient satisfaction. There is no significant relationship between the accuracy of the first operative report and surgeon and patient satisfaction. There is a statistically significant relationship between patient and surgeon satisfaction.

Congenital pulmonary airway malformations (CPAMs) are rare sporadic lesions frequently associated with poor fetal prognosis. Type 3 CPAMs are characterized by small hyperechogenic cysts (<5 mm). Hydrops often develops secondarily, and the fetal survival rate is approximately 5% in this setting. We present a case of a large type 3 CPAM complicated by fetal hydrops. The lesion was detected at 19 gestational weeks (GW) and confirmed by fetal MRI at 29 GW. At 22 GW, a course of maternal steroids was given as a possible treatment of type 3 CPAM. Peritoneal-amniotic shunt was placed twice to reduce fetal ascites, with unsatisfactory results. Similarly, polyhydramnios was relieved by two amnioreductions, but redeveloped soon after. A baby girl was delivered spontaneously at 33 GW and received a two-stage partial lobectomy in the first three months of life. Desaturations necessitated challenging invasive oscillatory ventilation between stages. Her outcome is unexpectedly positive and she may expect a good quality of life. She now approaches one year of age, with near-to-normal growth and developmental milestones. Type 3 CPAMs complicated by fetal hydrops are associated with high perinatal mortality. While open fetal surgery remains a viable option in select specialist centers, antenatal interventions are typically ineffective. The survival of this infant can be attributed to prenatal management and early postnatal surgical intervention. The lack of guidelines for ventilation in this setting was a significant challenge for neonatal intensivists. Multidisciplinary vigilance and collaboration with frequent specialist follow ups were the key to success for both mother and child.