Secondary capillary leak syndrome (SCLS) is a rare and frequently underrecognized cause of progressive edema, hypoalbuminemia, and noncardiogenic pulmonary edema. We present a case of a 55-year-old man with seronegative rheumatoid arthritis and antisynthetase syndrome on chronic immunosuppression who developed progressive bilateral lower-extremity edema and pulmonary edema in the absence of cardiac, renal, or hepatic disease. Extensive evaluation excluded alternative etiologies. The patient met diagnostic criteria for SCLS and demonstrated clinical improvement with albumin-assisted diuresis. This case highlights an underrecognized autoimmune-mediated phenotype of SCLS and underscores the importance of recognizing progressive edema without shock as a manifestation of SCLS.

Amiodarone is a widely used antiarrhythmic agent. Pulmonary toxicity is its most feared non-cardiac complication and is classically associated with high doses and prolonged duration of therapy. We report a case of early-onset amiodarone pulmonary toxicity (APT) developing after approximately one month of standard-dose amiodarone therapy (400 mg/day) in the setting of concurrent decompensated heart failure with preserved ejection fraction (HFpEF), which substantially complicated the diagnostic evaluation. A 71-year-old male with paroxysmal atrial fibrillation, nonischemic cardiomyopathy, and multiple comorbidities was initiated on amiodarone 400 mg/day in April. Within one month, he developed progressive dyspnea on exertion and productive cough. He presented to the emergency department in September with acute hypoxic respiratory failure (SpO₂ 86% on room air), weight gain, and bilateral lower extremity edema approximately five months after symptom onset. CT of the chest demonstrated bilateral ground-glass and consolidative opacities with upper lobe predominance and interlobular septal thickening. The initial working diagnosis of decompensated HFpEF was supported by elevated BNP and peripheral edema; intravenous furosemide led to the resolution of edema but no improvement in oxygenation. APT was subsequently suspected, and intravenous methylprednisolone was initiated, resulting in marked clinical improvement. The patient was discharged on room air on a prolonged prednisone taper. At the three-month follow-up, he demonstrated complete symptomatic resolution, marked radiological improvement, and normalization of BNP. This case adds to the existing evidence that clinically significant APT may occur at standard maintenance doses and within a shorter timeframe than traditionally recognized. Coexistent HFpEF poses a major diagnostic challenge given the substantial overlap in clinical and radiological features. The possibility of concurrent rather than competing pathology should always be considered. Clinicians should maintain a high index of suspicion for APT in any patient on amiodarone with progressive respiratory symptoms, irrespective of dose or duration of exposure.

Background/Objectives: Chronic diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) remain a major source of morbidity, healthcare utilization, and limb loss, despite adherence to established standards of care protocols and the widespread availability of advanced wound technologies. Many advanced modalities only target isolated aspects of wound healing and fail to address the complex, interdependent pathophysiology of chronic wounds, particularly tissue hypoxia, edema, impaired microcirculation, and persistent inflammation. Cyclical Pressurized Topical Wound Oxygen (TWO2) therapy is a home-based, multimodal intervention that combines humidified topical oxygen delivery with cyclical non-contact compression to address these core drivers simultaneously. Methods: This review synthesizes mechanistic rationale and evidence from randomized controlled trials, long-term venous ulcer studies, and real-world comparative effectiveness analyses. Emphasis is placed on the large cohort study by Yellin et al., which directly compared TWO2 with other advanced modalities including negative pressure wound therapy (NPWT), skin substitutes, and growth factor therapies. Results: Across these studies, TWO2 therapy is consistently associated with improved healing durability, reduced recurrence, and substantial reductions in hospitalization and amputation rates compared with both standard care and advanced wound therapies. Conclusions: The convergence of randomized and real-world evidence supports TWO2 therapy as a clinically meaningful and mechanism-driven adjunctive treatment option for patients with chronic, high-risk lower-extremity wounds.

Heart failure in the perinatal period remains ambiguous in definition and management despite its recognition as a unique disease state. The true incidence and prevalence of heart failure or left ventricular systolic dysfunction during pregnancy and the postpartum period are unknown, although a prevalence as high as 1% to 2% has been reported in the general adult US population. Assessment of heart failure can be challenging in the pregnant or postpartum state, during which symptoms affecting physical function (eg, dyspnea, exercise intolerance, fatigue, and lower-extremity edema) are prevalent because of physiological changes. Delays in the recognition and diagnosis of heart failure during the perinatal period contribute to adverse maternal outcomes, highlighting the need for evidence-based definitions and thresholds, improved diagnostic criteria to aid disease recognition, and effective screening tools. This scientific statement focuses on heart failure with reduced and mildly reduced ejection fraction in the context of pregnancy and the postpartum period, caused by various forms of cardiomyopathy. It addresses challenges related to recognizing heart failure in obstetric patients, outlines established treatment standards, and underscores potential areas for research. To improve the management of preexisting and de novo heart failure in obstetric patients, standardization of disease definitions, specific therapeutic options, implementation of effective screening tools, and interventions to improve maternal health equity are imperative. Future directions include prioritizing the inclusion of pregnant and postpartum individuals in heart failure studies, implementing interventions that facilitate early disease detection, and ensuring the timely initiation of appropriate therapies with the goal of reducing adverse outcomes associated with perinatal heart failure.

Kaposi sarcoma (KS) is an acquired immunodeficiency syndrome (AIDS)-defining malignancy that can involve the skin, lymph nodes, and visceral organs in patients with advanced human immunodeficiency virus (HIV). We report the case of a 35-year-old man with no known prior medical history who presented to the charity care clinic complaining of recurrent thrush and two weeks of progressive right lower extremity swelling. His physical examination revealed painful, pruritic violaceous papules and plaques over the proximal right thigh that had been present for one week. He was referred to the emergency department (ED) for further workup. Venous duplex ultrasonography was negative for deep venous thrombosis (DVT). He was found to have a newly diagnosed HIV-1 infection with advanced immunosuppression, oral thrush with odynophagia and dysphagia concerning for esophageal candidiasis, and a reactive rapid plasma reagin titer of 1:32 with retinal white dot lesions concerning for ocular syphilis. Computed tomography (CT) demonstrated diffuse right lower extremity soft tissue edema, extensive right inguinal, external iliac, and intrapelvic lymphadenopathy, bilateral axillary lymphadenopathy, and multiple bilateral pulmonary nodules. Punch biopsy of a right thigh lesion revealed KS with tumor cells positive for cluster of differentiation 31 (CD31), CD34, ERG, and human herpesvirus 8 (HHV-8), and an excisional lymph node biopsy demonstrated findings consistent with disseminated KS. Furthermore, cerebrospinal fluid (CSF) analysis confirmed neurosyphilis with a positive Venereal Disease Research Laboratory (VDRL). He was treated with bictegravir/emtricitabine/tenofovir alafenamide, trimethoprim-sulfamethoxazole prophylaxis, fluconazole, and intravenous penicillin G. The patient showed early clinical improvement with resolution of ocular symptoms and a declining HIV viral load following initiation of therapy and before discharge. This case highlights biopsy-proven KS as the presenting manifestation of previously undiagnosed advanced HIV, with unilateral limb lymphedema and pulmonary nodules suggesting disseminated disease. Additionally, our case underscores the need for early HIV testing in patients with recurrent mucocutaneous candidiasis and unexplained lymphedema, and for prompt evaluation of concomitant opportunistic and sexually transmitted infections.

We report a case of leiomyosarcoma of the inferior vena cava (IVC) treated with liver resection, autotransplantation, and IVC reconstruction using a Dacron graft. A 47-year-old female presented with mild to moderate lower extremity edema and weakness. Physical examination revealed no abdominal or pelvic abnormalities. However, further evaluation confirmed a tumor in the suprarenal IVC, extending to the hepatic veins, with thrombus formation in the suprahepatic IVC. During surgery, the tumor was confirmed to originate from the IVC. Given its proximity to the hepatic veins, an ex vivo liver resection and autotransplantation (ELRA) were performed, followed by IVC reconstruction using a Dacron graft via the piggyback technique. The patient experienced no postoperative complications. Although liver resection and autotransplantation are considered extremely aggressive procedures, they can be viable options in cases where complete surgical resection is not feasible using standard techniques.

Long-term indwelling inferior vena cava filters can cause device fracture and chronic caval occlusion, leading to deep vein thrombosis. Clinicians should consider filter-related complications in patients with a history of inferior vena cava filter placement who present with lower extremity edema or thrombosis even many years after placement.

Hydroxychloroquine (HCQ) is a cornerstone in treating autoimmune diseases and is generally well-tolerated. Cardiotoxicity is a rare but serious adverse effect of prolonged HCQ therapy. The progression of cardiac dysfunction may evade early detection with standard noninvasive investigations. This case report was prepared in accordance with the CABARET guidelines from the EQUATOR Network. The patient underwent comprehensive clinical evaluation for diagnostic clarification. A 57-year-old woman with Sjogren's disease (SjD) who was treated with HCQ 400 mg daily for nearly 21 years (cumulative dose ~ 3,000 g). The patient started to develop symptoms of syncope, shortness of breath and lower extremity edema. Noninvasive evaluation including echocardiography, coronary angiography, and cardiac magnetic resonance imaging failed to identify a clear etiology, demonstrating preserved ventricular size and systolic function without evidence of infiltrative or inflammatory cardiomyopathy. Continued decline in the patient's clinical status in addition to lack of response to medical therapy, an endomyocardial biopsy (EMB) was performed and revealed findings consistent with HCQ induced cardiotoxicity. HCQ was stopped; however, the damage was beyond reversal, so the patient ended up having an orthotopic heart transplantation. This case sheds light on an irreversible HCQ-induced cardiotoxicity that ended up with a heart transplantation. Despite extensive cardiac workup this adverse effect remained undetected until advanced disease. Delayed diagnosis can lead to irreversible cardiac damage and EMB should be considered in patients on prolonged HCQ therapy with unexplained cardiac symptoms and nondiagnostic workup. This can prompt early discontinuation of HCQ with potentially reversible damage and more favorable outcomes.

A 60-year-old woman presented with intermittent chest discomfort for 1 month, which had worsened over the preceding week and was accompanied by progressive dyspnea. Her medical history was notable for hepatitis approximately 40 years earlier. On admission, physical examination revealed jugular venous distention, cardiomegaly, and bilateral pitting edema of the lower extremities. Laboratory testing showed an NT-proBNP level of 8,272 pg/mL and a d-dimer level of 7,948 ng/mL. Computed tomography pulmonary angiography (CTPA) revealed bilateral thrombi in the main pulmonary arteries. Transthoracic echocardiography showed marked biventricular enlargement (LVEF 20%), 2 mural thrombi in the left ventricle, and a mobile thrombus in the right atrium. Lower extremity venous ultrasonography demonstrated deep vein thrombosis. Genetic testing using a cardiomyopathy gene panel identified a likely pathogenic TTN truncating variant (c.6061C>T, p.Arg2021*), consistent with the patient's phenotype of dilated cardiomyopathy (DCM). In conclusion, this case highlights the complex management of acute pulmonary embolism (PE) complicated by severe heart failure, multisite thrombosis, and acute hepatic congestion, emphasizing the critical need for individualized anticoagulation bridging and early adjunctive mechanical interventions.

ObjectivesChronic refractory lower-extremity edema often remains undiagnosed despite standard evaluations that focus primarily on excluding deep vein thrombosis. We aimed to elucidate the underlying etiologies and assess the utility of a comprehensive, structured diagnostic protocol.MethodsWe retrospectively analyzed a prospectively enrolled, referral-based cohort of 58 patients with chronic refractory lower- extremity edema who underwent a structured multimodal diagnostic protocol after failure of standard noninvasive evaluation. Etiologies were classified as non-thrombotic iliac vein lesions, pulmonary hypertension, superficial venous insufficiency, or multifactorial.ResultsNon-thrombotic iliac vein lesions, pulmonary hypertension, and superficial venous insufficiency were identified in 55.2%, 48.3%, and 43.1% of patients, respectively. Single etiologies accounted for 51.7% of cases, 41.4% were multifactorial, and 6.9% remained unclassified. Among pulmonary hypertension cases, isolated postcapillary pulmonary hypertension associated with heart failure with preserved ejection fraction was the most common (13.8%). Superficial venous insufficiency was the sole cause in 12.1% of cases, while in others, it coexisted with non-thrombotic iliac vein lesions or pulmonary hypertension. Interventions included iliocaval endovascular therapy (n = 23) and saphenous vein ablation (n = 10), with the remainder receiving conservative therapy. Over a median follow-up of 2.98 years, 86.2% of patients achieved objective clinical improvement.ConclusionsThis protocol reduced the number of repeated low-yield ultrasound examinations and facilitated targeted treatment. A structured diagnostic protocol integrating duplex ultrasonography, invasive hemodynamic testing, and intravascular imaging enables accurate etiologic classification of chronic refractory lower extremity edema. This approach identifies treatable contributors, supports tailored interventions, and may improve outcomes while reducing unnecessary testing.

BACKGROUND Salmonella enterica commonly causes self-limited gastroenteritis but can occasionally lead to invasive disease in predisposed hosts. Soft-tissue involvement is an uncommon complication, and the combination of bacteremia, cellulitis, and gastroenteritis has rarely been described. Cellulitis without abscess formation appears to be exceptionally rare. CASE REPORT A 75-year-old man with diabetes, peripheral arterial disease, and cirrhosis presented with right lower-extremity cellulitis following several days of non-bloody diarrhea. On examination, he was afebrile and hemodynamically stable, with edema extending from the foot to the mid-shin and an ulcer on the posterolateral calf. Imaging showed diffuse subcutaneous edema without abscess. Blood cultures, wound cultures, and stool polymerase chain reaction (PCR) were positive for Salmonella enterica (pan-sensitive), confirming bacteremia, soft-tissue infection, and gastroenteritis. Cellulitis resolved with a 7-day course of intravenous ceftriaxone. Transthoracic echocardiography demonstrated no evidence of endocarditis, and repeat blood cultures obtained on hospital day 2 were negative. There was no recurrence at the 3-week and 3-month follow-ups. CONCLUSIONS Very few cases of Salmonella enterica infection with this triad of manifestations have been reported. The absence of abscess formation further distinguishes this presentation. Underlying vascular disease and skin disruption may have created a susceptible environment for infection through hematogenous seeding or direct inoculation. This case shows the importance of considering Salmonella species in atypical soft-tissue infections, particularly in patients with chronic vascular or metabolic disease and concurrent diarrheal illness, and emphasizes the need for early microbiologic diagnosis and targeted antimicrobial therapy to ensure a favorable outcome.

Congenital extrahepatic portosystemic shunts (CEPS) are rare congenital vascular malformations characterized by an abnormal communication between the hepatic portal venous system and the systemic venous system. Type Ⅱ CEPS preserves partial portal venous blood flow and can usually be treated with conventional surgery rather than solely relying on liver transplantation. To determine the optimal surgical methods and complication management strategies for type Ⅱ CEPS patients, we retrospectively analyzed 31 predominantly adult patients with type Ⅱ CEPS, documenting their surgical approaches and the occurrence of postoperative complications. Five surgical approaches were employed: 11 patients underwent shunt occlusion with 5 cases of complications; 5 patients underwent splenic vessels ligation with 2 cases of complications; 5 patients underwent shunt occlusion combined with splenic artery ligation with 4 cases of complications; 8 patients underwent shunt occlusion combined with distal splenorenal shunt with 3 cases of complications; and 2 patients with lower extremity edema underwent inferior vena cava shunt bypass surgery, with no significant complications observed. In conclusion, surgery centering on the shunt occlusion demonstrates promising therapeutic value and remains the mainstay in the treatment of type II CEPS. Meanwhile, postoperative complications remain a concern, necessitating long-term monitoring and management.