Progressive pancytopenia in a patient with a history of hematologic malignancy presents a diagnostic challenge because active hematologic disease and severe systemic illness can produce overlapping findings. We report a 74-year-old woman with previously treated mantle cell lymphoma who presented with fever, altered mental status, neutropenia, and multifocal pneumonia. During hospitalization, she developed rapidly progressive pancytopenia, prompting consideration of active hematologic disease, infection and critical illness, medication effects, and consumptive processes. Peripheral blood flow cytometry showed no immunophenotypic evidence of a lymphoproliferative disorder or acute leukemia. However, this finding did not establish the cause of the cytopenias. Her pneumonia progressed despite broad-spectrum antimicrobial therapy, and bronchoalveolar lavage cultures grew Stenotrophomonas maltophilia. She developed respiratory failure and shock requiring mechanical ventilation and vasopressor support, followed by refractory multiorgan failure. She died on hospital day 12. This case highlights the diagnostic challenge of rapidly progressive pancytopenia when severe pulmonary illness and a history of hematologic malignancy offer competing explanations. It emphasizes continual reassessment as serial hematologic and microbiologic findings reshape the differential diagnosis.

Excited Delirium Syndrome remains one of the most controversial topics in contemporary forensic pathology. Although the term has been increasingly challenged because of the lack of universally accepted diagnostic criteria and formal recognition within major nosological systems, episodes of severe psychomotor agitation associated with sudden death continue to represent a significant clinical and medico-legal concern. We report two cases of sudden death occurring during physical restraint in individuals presenting with severe agitation. The first case involved a 60-year-old man with a history of depression who threatened suicide by defenestration and was restrained by family members in a prone position with his limbs bound. The second case concerned a 40-year-old man with psychiatric comorbidities and a history of alcohol abuse who exhibited aggressive behaviour in a public setting and was restrained by police officers and healthcare personnel during transport to the hospital. These cases highlight the diagnostic challenges associated with deaths occurring during episodes of extreme agitation and restraint. In the absence of pathognomonic post-mortem findings, diagnosis requires a thorough multidisciplinary evaluation and careful exclusion of alternative causes of death. A narrative review is also provided to outline the current state of knowledge on the issue. Furthermore, the ongoing debate surrounding the terminology should not obscure the existence of a clinically recognisable syndrome characterised by acute agitation, altered mental status, and autonomic dysregulation. Collaboration among forensic pathologists, clinicians, toxicologists, psychiatrists, and law-enforcement personnel is essential to improve diagnostic accuracy, patient management, and medico-legal assessment in these complex cases.

Proton pump inhibitors (PPIs) are widely prescribed for the management of gastric acid-related diseases, such as gastroesophageal reflux disease (GERD), and are generally well tolerated, with few or mild adverse effects. We present a case of an elderly female patient who developed hypomagnesemia, a rare but serious complication associated with chronic PPI therapy. The patient had been receiving esomeprazole 40 mg daily for approximately 12 months. She developed secondary electrolyte disorders, with hypocalcemia being the most evident. Her clinical manifestations initially included muscle cramps and tremors, which progressed to a seizure and eventually to altered mental status with a positive Trousseau sign. Despite institutional constraints, PPI-associated hypomagnesemia was considered, and the patient improved following electrolyte replacement and discontinuation of esomeprazole. Because fractional excretion of magnesium could not be calculated, the mechanism of magnesium loss could not be definitively established. This report highlights the importance of considering PPI-associated hypomagnesemia, an infrequent but potentially serious adverse effect, in patients receiving prolonged PPI therapy who develop compatible clinical manifestations.

Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by epistaxis, telangiectasias, and arteriovenous malformations (AVMs). Clinical diagnosis of HHT is typically guided by fulfillment of the Curaçao criteria. HHT is a known risk factor for brain abscesses in the pediatric population, particularly in those with pulmonary AVMs, where intrapulmonary right-to-left shunting permits septic emboli to seed the brain. We report the case of a 9-year-old girl with asthma and chronic sinusitis who presented with 5 days of congestion, cough, and worsening headache in the setting of Coronavirus Disease 2019 infection. Due to persistent hypoxia and transient altered mental status, further evaluation was pursued, with brain magnetic resonance imaging revealing multiple ring-enhancing lesions and chest computed tomography (CT) demonstrating multiple pulmonary nodules. CT angiography confirmed diffuse pulmonary AVMs. Culture from a brain biopsy grew Streptococcus intermedius. Whole-genome sequencing identified a de novo heterozygous SMAD4 variant, supporting a molecular diagnosis of juvenile polyposis/HHT syndrome. This case illustrates an atypical presentation and early diagnosis of this syndrome, prompted by the incidental finding of multiple subclinical brain abscesses. It underscores the value of maintaining a broad differential and performing targeted diagnostic studies when encountering brain abscesses of unclear origin. Pulmonary AVMs should be considered as a potential etiology of brain abscess, particularly in patients with concomitant hypoxemia and when endocarditis has been excluded. Furthermore, genetic evaluation for HHT should be considered in pediatric patients with unexplained or multifocal brain abscesses, even when the Curaçao criteria are not met, as early recognition may help prevent neurologic complications.

This article reports the management of a patient with Hodgkin lymphoma (HL) complicated by refractory critical autoimmune hemolytic anemia (AIHA) and explores the value of whole blood exchange (WBE) after failure of conventional therapy and plasma exchange. The patient was a 52-year-old woman with a history of classical HL treated with anti-PD-1 therapy. She was admitted due to progressive fatigue and altered mental status, with a nadir hemoglobin level of 24 g/L and a positive direct antiglobulin test for both anti-immunoglobulin G and anti-C3d (1:256). She also presented with impaired consciousness and shock, leading to a diagnosis of critical AIHA. The patient failed to respond to multiple lines of treatment, including high-dose corticosteroids, intravenous immunoglobulin, rituximab, eculizumab, and plasma exchange, and experienced recurrent hypotension. After multidisciplinary consultation, WBE was performed. Within 24 hours after the procedure, her urine color turned from dark tea-colored to light yellow, with no recurrence of dark urine. The hemoglobin level increased to 52 g/L on day 5 and to 63 g/L on day 10 post-procedure. The lactate dehydrogenase level decreased from a peak level of 2 304 U/L to 481 U/L, and the total bilirubin level dropped to 20.4 μmol/L. The patient's hemodynamic status stabilized, and she was transferred out of the hematological intensive care unit on day 16. The present case demonstrates that for severe AIHA refractory to conventional immunosuppression and plasma exchange, WBE can rapidly remove sensitized erythrocytes and complement components, serving as an effective rescue therapy.

Radiotherapy (RT) is an important part of curative treatment in many common abdominal and pelvic cancers. However, the gastrointestinal toxicities can affect the quality of life and outcomes for many patients. The underlying local gut toxicity and systemic effects, including effects on mental health, are underexplored and poorly understood. Given emerging evidence of immunological communication across the gut-brain axis, we investigated whether abdominal RT could induce distal immune alterations in the dural meninges and explored potential behavioural outcomes. Using a preclinical model of image-guided abdominal RT treatment, we induced a local myeloid-driven inflammatory response in the small intestine and colon. We observed significant systemic immune modulations in the peripheral blood and dural meninges, affecting a diverse range of immune cells. Whilst circulating immune changes largely resolved alongside recovery of intestinal inflammation, dural immune alterations were prolonged and dynamically shifted across time points. Depletion of the gut microbiota partially attenuated both local and systemic immune responses, particularly affecting RT-induced increases in neutrophil and monocyte populations, implicating microbiota-dependent mechanisms in mediating these effects. After recovery from acute intestinal toxicity, RT-treated mice displayed increased anxiety-like phenotypes without evidence of cognitive impairment. Collectively, these findings demonstrate that gut-targeted RT can drive systemic immunomodulatory effects that extend to the brain border tissues in a partially microbiota-dependent manner and can enhance anxiety-like behaviour in mice. This highlights the systemic immune consequences of RT beyond the targeted tissue site, and the potential importance of RT-mediated immune organ crosstalk in mediating therapy outcomes.

Depression is a major and under-recognized comorbidity in Sjögren's disease, contributing to disease burden and impaired quality of life. This narrative review summarizes current evidence regarding the prevalence, pathophysiological mechanisms, clinical impact, assessment, and treatment of depression in patients with Sjögren's disease. Reported prevalence rates range widely from 3.2% to 78.6%, largely owing to methodological heterogeneity, although meta-analytic data demonstrate a significantly increased risk of depression in patients with Sjögren's disease than in healthy controls. Etiology is multifactorial, involving chronic pain, fatigue, dryness, psychosocial stressors, and immune-mediated mechanisms. Elevated inflammatory cytokines, altered serotonergic pathways, antibodies, gut dysbiosis, and neuroimaging abnormalities are the potential underlying links to depression. Furthermore, depression is associated with greater symptom burden, autonomic dysfunction, sleep disturbances, fatigue, reduced health-related quality of life, and impaired functional status. Patient-reported outcomes often correlate more closely with depression than with systemic disease activity. Although several screening instruments are available, their validation in patients with Sjögren's disease remains limited. Management requires a multidisciplinary approach integrating psychological interventions, lifestyle modification, and pharmacologic treatment. Selective serotonin reuptake inhibitors and other agents with low anticholinergic burden are preferred. Optimization of systemic disease control may provide additional benefits. Early recognition and comprehensive management of depression are essential to improve outcomes in patients with Sjögren's disease.