Lung ultrasound and diuretic therapy in chronic heart failure: a randomised trial.

BACKGROUND: Lung congestion is frequent in heart failure (HF) and is associated with symptoms and poor prognosis. Lung ultrasound (LUS) identification of B-lines may help refining congestion assessment on top of usual care. Three small trials comparing LUS-guided therapy to usual care in HF suggested that LUS-guided therapy could reduce urgent HF visits. However, to our knowledge, the usefulness of LUS in influencing loop diuretic dose adjustment in ambulatory chronic HF has not been studied. AIMS: To study whether to show or not LUS results to the HF assistant physician would change loop diuretic adjustments in "stable" chronic ambulatory HF patients. METHODS: Prospective randomised single-blinded trial comparing two strategies: (1) open 8-zone LUS with B-line results available to clinicians, or (2) blind LUS. The primary outcome was change in loop diuretic dose (up- or down-titration). RESULTS: A total of 139 patients entered the trial, 70 were randomised to blind LUS and 69 to open LUS. The median (percentile25-75) age was 72 (63-82) years, 82 (62%) were men, and the median LVEF was 39 (31-51) %. Randomisation groups were well balanced. Furosemide dose changes (up- and down-titration) were more frequent among patients in whom LUS results were open to the assistant physician: 13 (18.6%) in blind LUS vs. 22 (31.9%) in open LUS, OR 2.55, 95%CI 1.07-6.06. Furosemide dose changes (up- and down-titration) were more frequent and correlated significantly with the number of B-lines when LUS results were open (Rho = 0.30, P = 0.014), but not when LUS results were blinded (Rho = 0.19, P = 0.13). Compared to blind LUS, when LUS results were open, clinicians were more likely to up-titrate furosemide dose if the result "presence of pulmonary congestion" was identified and more likely to decrease furosemide dose in the case of an "absence of pulmonary congestion" result. The risk of HF events or cardiovascular death did not differ by randomisation group: 8 (11.4%) in blind LUS vs. 8 (11.6%) in open LUS. CONCLUSIONS: Showing the results of LUS B-lines to assistant physicians allowed more frequent loop diuretic changes (both up- and down-titration), which suggests that LUS may be used to tailor diuretic therapy to each patient congestion status.

The platelet-to-lymphocyte ratio as an indirect outcome predictor in primary hypertension: a retrospective study.

Background: Nondipper hypertensive patients have higher levels of platelet-to-lymphocyte ratio, a new studied inflammatory biomarker in primary hypertension. Furthermore, these patients have a higher risk of cardiovascular morbidity and mortality. This study aimed to assess the relationship between platelet-to-lymphocyte ratio and hypertensive pattern (dipper vs nondipper) and the association between the hypertensive pattern and major adverse cardiovascular events. Methods: A retrospective analysis was performed. One hundred fifty-three patients were included and classified as dipper or nondipper according to 24-hour ambulatory blood pressure measurements. Platelet-to-lymphocyte ratio was calculated based on complete blood count data. Results: The dipper group included 109 patients, and the nondipper group included 44 patients. Nondipper patients have 2.11 more risk of presenting a higher platelet-to-lymphocyte ratio than dipper individuals (odds ratio [OR] = 2.11; 95% CI, 1.220-3.664; P = .007). Nondipper patients also registered earlier cardiovascular events, such as acute myocardial infarction and stroke (P < .001). Conclusions: Nondipper hypertensive individuals registered higher levels of platelet-to-lymphocyte ratio and earlier cardiovascular events than dipper patients. Therefore, platelet-to-lymphocyte ratio could be used as an indirect predictor of cardiovascular risk in primary hypertension and contribute to optimize preventive strategies.

Cytomegalovirus and Hemolytic Anemia in an Immunocompetent Adult.

Hemolytic anemia is an increasingly recognized complication of cytomegalovirus (CMV) infection in immunocompetent patients. Although it is thought to be immune-mediated, other mechanisms have been proposed. The decision to treat is controversial but it may include antiviral and immunosuppressive therapy. We report a case of CMV-induced hemolytic anemia in a previously healthy 55-year-old woman. The patient presented with asthenia and choluria, and laboratory tests showed severe anemia with hyperbilirubinemia and elevated lactate dehydrogenase. A diagnosis of hemolytic anemia was made. Structural, enzymatic, toxic, pharmacological, and neoplastic causes were excluded. The CMV immunoglobulin M was positive, with a negative direct antiglobulin test. The patient had an improvement in clinical and laboratory status without any treatment, and two months later she had a full recovery of the anemia. This case illustrates that CMV infection might be associated with severe organ damage in immunocompetent patients but has an overall good prognosis without any directed treatment.

Acute Myeloid Leukaemia Presenting as B12 Vitamin Deficiency When Multiple Horses Become a Zebra.

Vitamin B12 deficiency is a common finding in medical practice. It is easily treated with supplementation and typically has a favourable prognosis. In rare circumstances, it can hide a severe disease that should be promptly addressed. We report the case of an acute myeloid leukaemia presenting as an initially predictable B12 deficiency in a vegetarian patient with chronic gastritis. The supplementation rapidly corrected the deficit and the accompanying cytopenias. However, in the following month the cell counts fell once again, leading to the suspicion that other aetiology could be lying beneath the surface. Maintaining a normal peripheral blood smear, the bone marrow biopsy showed myeloblasts and extensive fibrosis compatible with the diagnosis of acute myeloid leukaemia. The neoplasm justified the vitamin deficit by excessive cellular turnover, a vicious cycle only uncovered after supplementation and that ultimately led to the patient's death. LEARNING POINTS: Vitamin B12 is a common aetiology of pancytopenia and is usually caused by gastric malabsorption.When supplementation does not correct the haematological deficit, central causes must be considered. Acute myeloid leukaemia is one possibility, but causes peripheral blood smear abnormalities in almost all patients. Diagnosis should include lumbar puncture and a thorough search for the aetiology; treatment is directed towards the aetiology.Neoplastic diseases should be always excluded when correction of the deficit does not resolve cytopenias.

Uveo-Meningitis and Myelodysplastic Syndrome.

Uveo-meningeal syndromes are any disorder characterized by the involvement of the uvea and the meninges. They can have multiple causes, including infectious, autoimmune and malignant diseases. We report the case of a patient with a 10-year-old diagnosis of myelodysplastic syndrome that had been stable. He presented with new onset uveitis, ataxia, diplopia and fluctuating consciousness level, without any obvious cause revealed by brain imaging or blood chemistries. An extensive aetiological search showed no obvious cause. Initially, the patient improved spontaneously and was discharged. However, 2 months later, he deteriorated once again, this time with disperse adenomegalies that were not present previously. The bone marrow biopsy showed a high number of blasts, which affirmed the progression of the previously known myelodysplastic syndrome. The lymph nodes were not biopsied due to very low life expectancy, making the procedure futile. A presumptive diagnosis of uveo-meningitis caused by paraneoplastic syndrome was made. The patient died a few months later. LEARNING POINTS: Uveo-meningeal syndrome (UMS) is a rare entity usually of infectious or inflammatory aetiology.UMS may be caused by some neoplastic disorders, mainly lymphoma and metastasis of solid tumours; myelodysplastic syndrome (MDS) has not been previously implicated.Diagnosis should include lumbar puncture and a thorough search for the aetiology; treatment is directed towards the aetiology.

Fenofibrate and Heart Failure Outcomes in Patients With Type 2 Diabetes: Analysis From ACCORD.

OBJECTIVE: Patients with type 2 diabetes (T2D) have a high risk for developing heart failure (HF), which is associated with poor prognosis. Fenofibrate may reduce HF events through multiple mechanisms. We sought to study the effect of fenofibrate (vs. placebo) in HF outcomes among patients with T2D receiving simvastatin enrolled in the Action to Control Cardiovascular Risk in Diabetes lipid trial (ACCORD Lipid). RESEARCH DESIGN AND METHODS: We used Cox regression analysis with background glucose-lowering strategy as the stratification variable. The median follow-up was 4.7 years. RESULTS: A total of 5,518 patients were included. Median age was 62 years, and 31% were women. Prior HF history was present in 5% of the patients. The composite outcome of HF hospitalization or cardiovascular death occurred in 190 (6.9%) patients in the fenofibrate group vs. 228 (8.3%) in the placebo group: HR 0.82, 95% CI 0.68-1.00 (P = 0.048). The beneficial effect of fenofibrate to reduce HF hospitalizations or cardiovascular death was present among patients receiving standard glucose-lowering strategy, HR 0.64, 95% CI 0.48-0.85, and not among patients receiving intensive glucose-lowering strategy, HR 1.02, 95% CI 0.79-1.33 (Pinteraction = 0.017). A similar pattern was observed for HF hospitalizations alone. The effect of fenofibrate on blood lipids was not influenced by background glucose-lowering therapy in a clinically important manner. Fenofibrate caused more transient worsening estimated glomerular filtration rate (eGFR) events but slowed long-term eGFR decline. CONCLUSIONS: In patients with T2D treated with simvastatin, fenofibrate reduced the composite of HF hospitalizations or cardiovascular mortality, an effect that was seen predominantly in patients with standard background glucose-lowering therapy.

Pulmonary Adenocarcinoma Presenting as Acute Heart Failure and Hypereosinophilia.

Hypereosinophilia is a serum eosinophil count of over 1,500 eosinophils/µL. It is an uncommon laboratory finding, and it can be asymptomatic or associated with organ damage, in which case it is referred to as hypereosinophilic syndrome. It can be primary, when the expansion of eosinophils occurs in the setting of a hematological neoplasm, or secondary, when it is caused by an external stimulus, such as a parasitic infection or a solid neoplasm. We present a case of hypereosinophilia diagnosed in a patient presenting with acute heart failure initially attributed to coronary disease and alcohol consumption. Due to persisting eosinophilia with no apparent cause, eventually reaching more than 41,000 eosinophils/µL, a full-body scan was performed, showing the presence of a peri-hilar mass partially obstructing the left main bronchus and multiple lesions in the liver and thoracic vertebrae. The liver biopsy revealed metastatic non-small cell lung carcinoma. Around the time the biopsy was performed, the patient began complaining of new-onset chest paint, and the diagnoses of pulmonary embolism and later lung abscess were made, the reasons why he had no conditions to begin chemotherapy. The medical condition of the patient deteriorated in the next few days, and the patient died six months after the initial diagnosis of hypereosinophilia.

Platypnea-Orthodeoxia Syndrome: A Rare Cause of Positional Respiratory Failure.

Platypnea-orthodeoxia syndrome (POS) is a rare clinical entity characterized by dyspnea and arterial desaturation in the upright position. Hypoxia in POS has been attributed to the mixing of deoxygenated venous with oxygenated arterial blood via a shunt, with patent foramen ovale being the most commonly reported abnormality. A systematic evaluation is necessary to identify the underlying cause and promote an appropriate intervention. Here, we present the case of a 79-year-old female with a new diagnosis of POS during the workup of hypoxemic respiratory failure.

Neurolisteriosis: The Importance of a Prompt Diagnosis.

Immune thrombocytopenia (ITP) is a prevalent disease that may need immunosuppressant treatment, which increases the risk of an opportunistic infection. We present the case of a woman with corticosteroid-resistant ITP who was electively admitted to the hospital to initiate second-line treatment. On the second day, she presented with a high fever and altered mental status, with no lesions on the cerebral tomography and inconclusive cerebrospinal fluid analysis. Nonetheless, she was promptly started on empiric antibiotics for meningitis which were then adjusted for Listeria monocytogenes, isolated in blood culture. The cerebral magnetic resonance showed signs of cerebritis and pyogenic foci. The patient was discharged after 73 days of treatment, asymptomatic and with no neurological sequelae. The mortality rate of neurolisteriosis can be as high as 50%. The median time between the initial symptoms and their detection is seven days, with many patients already developing cerebral abscesses. The favorable outcome of this patient was due to the precocious detection and start of the treatment.

Interplay between worsening kidney function and cardiovascular events in patients with type 2 diabetes: an analysis from the ACCORD trial.

INTRODUCTION: Patients with type 2 diabetes (T2D) have an increased risk of worsening kidney function (WKF) over time compared with patients without diabetes. Data evaluating the inter-relation between WKF, cardiovascular risk, and clinical events are scarce. We aim to study the association of WKF with subsequent cardiovascular events and the probabilities of transition from WKF to hospitalization or death according to patients' risk. We have used a large population of patients with T2D and a high cardiovascular risk enrolled in the Action to Control Cardiovascular Risk in Diabetes Study. RESEARCH DESIGN AND METHODS: Time-updated, joint, and multistate modeling were used. WKF was defined as an estimated glomerular filtration rate (eGFR) decline greater than 40% from baseline. A total of 10 251 patients were included, of whom 1213 (11.8%) presented WKF over a median (percentile25-75) follow-up time of 5.0 (4.1-5.7) years. RESULTS: Patients who experienced WKF were slightly older, more frequently women, and had longer diabetes duration. Patients experiencing WKF, regardless of baseline kidney function, had a higher risk of subsequent cardiovascular events, including the composite of cardiovascular death or hospitalization for heart failure (HHF), with ≈2-fold higher risk. Joint modeling showed that renal function deterioration frequently occurs even among patients who did not experience a cardiovascular event. In multistate models, patients with a medium-high cardiovascular risk (compared with those with a low cardiovascular risk) are at higher risk of HHF or cardiovascular death first (HR=4.76, 95% CI 3.63 to 6.23) than of WKF first (HR=1.37, 95% CI 1.21 to 1.56); remarkably, the risk of cardiovascular death or HHF is highest after a WKF event (HR=6.20, 95% CI 2.71 to 14.8). CONCLUSIONS: In patients with T2D and a high cardiovascular risk, WKF occurs in more than 10% of patients and is independently associated with risk of subsequent cardiovascular events, irrespective of baseline eGFR. Preventing serious WKF and the transition from WKF to HHF or cardiovascular death is an important objective of future trials. TRIAL REGISTRATION NUMBER: NCT00000620.

Cerebral Venous Thrombosis after BNT162b2 mRNA SARS-CoV-2 vaccine.

The development of SARS-CoV-2 vaccines has raised several concerns regarding venous thromboembolism, namely cerebral venous thrombosis. Although cerebral venous thrombosis has been reported after administration of a viral vector vaccine, due to a possible auto-immune mechanism inducing thrombocytopenia, the same has not happened in mRNA vaccines. We report two cases of cerebral venous thrombosis, shortly after administration of mRNA vaccine. In both patients, there was no evidence of thrombocytopenia or antiplatelet antibodies, and alternative causes for cerebral venous thrombosis were found. As such, despite the temporal relation of both cases to vaccine administration, these types of cerebral venous thrombosis do not seem to be pathophysiological different from cerebral venous thrombosis not associated to SARS-CoV-2 vaccination. Continuous pharmacovigilance is necessary to monitor possible new events and clarify this association.