The aim of this study was to evaluate the influence of surgical cytoreduction on survival in patients with Stage IV epithelial ovarian cancer and to determine the survival impact of debulking extrahepatic disease in the subgroup of patients with liver metastasis.

Medical records were retrospectively reviewed for all women with International Federation of Gynecology and Obstetrics Stage IV ovarian cancer treated between 1/1/82 and 12/31/94. Clinical information abstracted included age at diagnosis, performance status, histologic subtype, tumor grade, Stage IV criteria, ascites volume, predominant peritoneal tumor pattern, surgical procedures performed, hepatic tumor residuum, extrahepatic tumor residuum, and postoperative complications. Optimal surgical status was defined as residual disease </=1 cm. Chemotherapy treatment and follow-up were recorded. Survival analysis and comparisons were performed using the Kaplan-Meier method and the log-rank test. The Cox proportional hazards regression model was used to identify independent variables associated with an improved survival rate.

There were 84 women with Stage IV ovarian cancer and complete operative and postoperative information available. Median age at diagnosis was 61 years (range 26-85 years). Performance status was </=2 in 83% of patients (70/84). Papillary serous histology was found in 44/84 patients (52%) and 55 patients (65%) had grade 3 tumors. Thirty-seven of 84 patients (44%) had parenchymal liver metastasis and 32/84 (38%) had malignant pleural effusion. Overall median survival was 18.1 months and was highly correlated with performance status (P = 0.002), predominant peritoneal tumor pattern (P = 0.0002), and the number of chemotherapy regimens received (P = 0.0039). Primary surgical cytoreduction was attempted in all patients and 25/84 (30%) achieved optimal status. Median survival of optimally cytoreduced patients was 38.4 months, compared to 10.3 months for patients with suboptimal residual disease (P = 0.0004). In patients with liver metastasis, optimal extrahepatic cytoreduction was achieved in 46% (17/37). Six of 37 patients (16%) underwent optimal resection of both extrahepatic and hepatic disease and had a median survival of 50.1 months, compared to a median survival of 27.0 months for the 11 patients (30%) with optimal extrahepatic disease but suboptimal residual hepatic tumor. Twenty patients (54%) were left with both suboptimal residual extrahepatic and hepatic disease and had a median survival of 7.6 months (P = 0.0001). Optimal debulking surgery and performance status retained significance as independent predictors of survival on multivariate analysis.

Optimal surgical debulking and performance status appear to be important determinants of survival in patients with Stage IV epithelial ovarian cancer. Even in patients with unresectable liver metastasis, optimal debulking of extrahepatic disease is associated with a significant survival advantage.

Survival impact of surgical cytoreduction in stage IV epithelial ovarian cancer.

Gynecologic Oncology

Diabetic kidney disease (DKD), defined as co-existing diabetes and chronic kidney disease in the absence of other clear causes of kidney injury, occurs in approximately 20-40% of patients with diabetes mellitus. As the global prevalence of diabetes has increased, DKD has become highly prevalent and a leading cause of kidney failure, accelerated cardiovascular disease, premature mortality and global health care expenditure. Multiple pathophysiological mechanisms contribute to DKD, and single lifestyle or pharmacological interventions have shown limited efficacy at preserving kidney function. For nearly two decades, renin-angiotensin system inhibitors were the only available kidney-protective drugs. However, several new drug classes, including sodium glucose cotransporter-2 inhibitors, a non-steroidal mineralocorticoid antagonist and a selective endothelin receptor antagonist, have now been demonstrated to improve kidney outcomes in people with type 2 diabetes mellitus. In addition, emerging preclinical and clinical evidence of the kidney-protective effects of glucagon-like-peptide-1 receptor agonists has led to the prospective testing of these agents for DKD. Research and clinical efforts are geared towards using therapies with potentially complementary efficacy in combination to safely halt kidney disease progression. As more kidney-protective drugs become available, the outlook for people living with DKD should improve in the next few decades.

Combination therapy for kidney disease in people with diabetes mellitus.

Nature Reviews. Nephrology

Volume overload represents a hallmark clinical feature linked to the development and progression of heart failure (HF). Alleviating signs and symptoms of volume overload represents a foundational HF treatment target that is achieved using loop diuretics in the acute and chronic setting. Recent work has provided evidence to support guideline-directed medical therapies, such as sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor (MR) antagonists, as important adjunct diuretics that may act synergistically when used with background loop diuretics in people with chronic HF. Furthermore, there is growing interest in understanding the role of SGLT2 inhibitors, carbonic anhydrase inhibitors, thiazide diuretics, and MR antagonists in treating volume overload in patients hospitalized for acute HF, particularly in the setting of loop diuretic resistance. Thus, the current review demonstrates that: 1) SGLT2 inhibitors and MR antagonists confer long-term cardioprotection in chronic HF patients but it is unclear if natriuresis or diuresis represents the primary mechanisms for this benefit, 2) SGLT2 inhibitors, carbonic anhydrase inhibitors, and thiazide diuretics increase natriuresis in the acute HF setting, but implications on long-term outcomes remain unclear and warrants further investigation, and 3) a multi-nephron segment approach, using agents that act on distinct segments of the nephron, potentiate diuresis to alleviate signs and symptoms of volume overload in acute HF.

Proximal versus distal diuretics in congestive heart failure.

Nephrology, Dialysis, Transplantation

The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary or clonal) disorders with the potential for end-organ damage.

Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5&#x2009;&#xd7;&#x2009;109 /L, and may be associated with tissue damage. After the exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ hybridization, molecular testing and flow immunophenotyping to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.

Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2022 World Health Organization and International Consensus Classification endorse a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions" (MLN-eo-TK), and the MPN subtype, "chronic eosinophilic leukemia" (CEL). Lymphocyte-variant HE is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.

The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (e.g., &lt;1.5&#x2009;&#xd7;&#x2009;109 /L) without symptoms or signs of organ involvement, a watch and wait approach with close follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Pemigatinib was recently approved for patients with relapsed or refractory FGFR1-rearranged neoplasms. Corticosteroids are first-line therapy for patients with lymphocyte-variant HE and HES. Hydroxyurea and interferon-&#x3b1; have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. Mepolizumab, an interleukin-5 (IL-5) antagonist monoclonal antibody, is approved by the U.S Food and Drug Administration for patients with idiopathic HES. Cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. Targeted therapies such as the IL-5 receptor antibody benralizumab, IL-5 monoclonal antibody depemokimab, and various tyrosine kinase inhibitors for MLN-eo-TK, are under active investigation.

World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.

American Journal of Hematology

Cardiogenic shock (CS) is characterized by low cardiac output and sustained tissue hypoperfusion that may result in end-organ dysfunction and death. CS is associated with high short-term mortality, and its management remains challenging despite recent advances in therapeutic options. Timely diagnosis and multidisciplinary team-based management have demonstrated favourable effects on outcomes. We aimed to review evidence-based practices for managing patients with ischemic and non-ischemic CS, detailing the multi-organ supports needed in this critically ill patient population.

Management of cardiogenic shock: a narrative review.

Annals of Intensive Care

Chronic insomnia affects 5% to 10% of the US population, increasing the demand for treatment options and the corresponding research to prove their validity.1 This review compares recommendations from 3 clinical guidelines and summarizes hypnotic medications, including their newly reported side effects not mentioned in the guidelines. In addition, we aim to provide an overview of what pharmacotherapies are available for prescribers and patients.

A literature search was conducted for articles published prior to January 10, 2022, and case reports and clinical studies were retrieved from PubMed and Google Scholar.

Definitive conclusions cannot be drawn regarding the safety and efficacy of medications reviewed; however, trends are apparent. All 3 guidelines included in this review remarked most treatment recommendations as weak except for cognitive behavioral therapy for insomnia, which is effective but not readily available. Furthermore, based on the 15 case reports and 13 clinical studies presented in this review, many of the medications used for treatment of insomnia present safety concerns.

Benzodiazepines and benzodiazepine receptor agonists are commonly used hypnotic agents with the "Z-drugs" having robust data establishing their efficacy for the short-term treatment of chronic insomnia. However, significant adverse effects related to the central nervous system (CNS), including developing tolerance, addiction, CNS depression, and amnesia, remain barriers to their long-term use. In comparison, newer agents present more favorable side-effect profiles although with less established efficacy. Additionally, off-label agents, including antidepressants, antihistamines, and natural supplements, are discussed due to their prominent use.

Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.

Mental Health Clinician

The aetiology of heart failure with preserved ejection fraction (HFpEF) is heterogenous and overlaps with that of several comorbidities like atrial fibrillation, diabetes mellitus, chronic kidney disease, valvular heart disease, iron deficiency, or sarcopenia. The diagnosis of HFpEF involves evaluating cardiac dysfunction through imaging techniques and assessing increased left ventricular filling pressure, which can be measured directly or estimated through various proxies including natriuretic peptides. To better narrow down the differential diagnosis of HFpEF, European and American heart failure guidelines advocate the use of different algorithms including comorbidities that require diagnosis and rigorous treatment during the evaluation process. Therapeutic recommendations differ between guidelines. Whilst sodium glucose transporter 2 inhibitors have a solid evidence base, the recommendations differ with regard to the use of inhibitors of the renin-angiotensin-aldosterone axis. Unless indicated for specific comorbidities, the use of beta-blockers should be discouraged in HFpEF. The aim of this article is to provide an overview of the current state of the art in HFpEF diagnosis, clinical evaluation, and treatment.

Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.

Clinical Research in Cardiology : Official Journal of the German Cardiac Society

The three pathophysiologic contributors to septic shock include varying combinations of hypovolemia (relative &gt; absolute), decreased vascular tone or vasoplegia, and myocardial dysfunction. The three pillars of hemodynamic support include fluid boluses, vasopressors with or without inotrope infusions. The three end-points of hemodynamic resuscitation include an adequate cardiac output (CO), adequate mean arterial pressure (MAP) and diastolic blood pressure (DBP) for organ perfusion, and avoiding congestion (worse filling) parameters. Only 33-50% of septic patients show post-fluid bolus CO improvements; this may be sustained in &#x2265;10% on account of sepsis-mediated glycocalyx injury. A pragmatic approach is to administer a small bolus (10 mL/kg over 20-30 min) and judge the response based on clinical perfusion markers, pressure elements, and congestive features. Vasoplegia marked by low DBP is a major contributor to hypotension in septic shock. Hence, a strategy of restricted fluid bolus with early low-dose norepinephrine (NE) (0.05-0.1 &#xb5;g/kg/min) can be helpful. NE may also be useful in septic myocardial dysfunction (SMD) as an initial agent to maintain adequate coronary perfusion and DBP while minimizing tachycardia and providing inotropy. Severe SMD may benefit from additional inotropy (epinephrine/dobutamine). Except vasopressin, most vasoactive drugs may safely be administered via a peripheral route. The lowest MAP (5th centile for age) may be an acceptable target, provided end-organ perfusion is satisfactory. A clinical individualized approach combining the history, serial physical examination, laboratory analyses, available monitoring tools, and repeated assessment to individualize circulatory support may to lead to better outcomes than one-size-fits-all algorithms.

Hemodynamic Management Strategies in Pediatric Septic Shock: Ten Concepts for the Bedside Practitioner.

Indian Pediatrics

Sudden cardiac death (SCD) accounts for a substantial proportion of mortality in heart failure with reduced ejection fraction (HFrEF), frequently triggered by ventricular arrhythmias (VA). This review aims to analyze the pathophysiological mechanisms underlying VA and SCD in HFrEF and evaluate the effectiveness of guideline-directed medical therapy (GDMT) in reducing SCD. Beta-blockers, angiotensin receptor-neprilysin inhibitors, and mineralocorticoid receptor antagonists have shown significant efficacy in reducing SCD risk. While angiotensin-converting enzyme inhibitors and angiotensin receptor blockers exert beneficial impacts on the renin-angiotensin-aldosterone system, their direct role in SCD prevention remains less clear. Emerging treatments like sodium-glucose cotransporter 2 inhibitors show promise but necessitate further research for conclusive evidence. The favorable outcomes of those molecules on VA are notably attributable to sympathetic nervous system modulation, structural remodeling attenuation, and ion channel stabilization. A multidimensional pharmacological approach targeting those pathophysiological mechanisms offers a complete and synergy approach to reducing SCD risk, thereby highlighting the importance of optimizing GDMT for HFrEF. The current landscape of HFrEF pharmacotherapy is evolving, with ongoing research needed to clarify the full extent of the anti-arrhythmic benefits offered by both existing and new treatments.

Anti-Arrhythmic Effects of Heart Failure Guideline-Directed Medical Therapy and Their Role in the Prevention of Sudden Cardiac Death: From Beta-Blockers to Sodium-Glucose Cotransporter 2 Inhibitors and Beyond.

Survival impact of surgical cytoreduction in stage IV epithelial ovarian cancer.

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Survival impact of surgical cytoreduction in stage IV epithelial ovarian cancer.

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