Ricin, a potent protein toxin derived from Ricinus communis, is considered one of the most significant threats in cases of bioterrorism, homicide, suicide, and accidental acute poisoning. However, its clinical and pathological features in fatal cases have not been systematically summarized. This systematic review aimed to summarize the current evidence regarding the clinical manifestations, toxicological biomarkers, autopsy findings, and medico-legal aspects of fatal ricin poisoning. A comprehensive literature search was conducted in accordance with PRISMA guidelines. Original studies, case reports, and case series reporting detailed clinical, toxicological, or autopsy data following fatal or near-fatal human exposure to ricin were included in the review. The available evidence suggests a relatively consistent clinical course, characterized by rapid progression from mild, nonspecific gastrointestinal symptoms to hypovolemic shock, multi-organ failure, and refractory cardiovascular collapse. Ricinine was consistently detected in blood, urine, and postmortem tissues, supporting its role as a reliable biomarker of ricin exposure, although current evidence is insufficient to establish definitive correlations with poisoning severity or toxicokinetics. Reported autopsy findings commonly included hemolysis, hemorrhagic necrosis of the gastrointestinal tract, hepatic injury, renal tubular necrosis, and evidence supporting the presence of a capillary leak syndrome. Several specific medico-legal challenges emerged from the reviewed literature, including the need for the development of novel analytical methods with improved detection limits and quantification capabilities for ricinine, the interpretation of postmortem redistribution phenomena, the distinction between lethal and non-lethal exposures, and the differential diagnosis with other septic shock-like syndromes. Overall, the available evidence suggests a relatively consistent clinicopathological pattern associated with fatal ricin poisoning that can be corroborated through ricinine detection, while emphasizing the importance of early toxicological investigations, particularly when no history of exposure is available. These findings provide a concise and integrated body of evidence to support clinical management, inform forensic investigations, and enhance public health preparedness, while highlighting the need for standardized postmortem sampling protocols and further research into the toxicodynamics of ricin in humans.

Hypothyroidism is a rare cause of rhabdomyolysis and an even less common cause of acute kidney injury (AKI). Because the symptoms may be mild or non-specific, the diagnosis can easily be overlooked. We report the case of a 44-year-old man with no significant past medical history who was admitted after renal impairment was discovered on routine blood testing. On clinical examination, he had sinus bradycardia, puffy facies with bilateral periorbital edema, Hertoghe sign, muffled heart sounds, psychomotor slowing, and constipation. Laboratory investigations showed stage II AKI, severe rhabdomyolysis with creatine phosphokinase levels above 8,450 IU/L (reference range: <171 IU/L), and liver cytolysis. Further evaluation revealed profound hypothyroidism, with markedly elevated thyroid-stimulating hormone, very low free thyroxine, and strongly positive anti-thyroid peroxidase antibodies, consistent with autoimmune thyroiditis. Thyroid ultrasound supported the diagnosis of Hashimoto's thyroiditis, and echocardiography showed a moderate pericardial effusion without hemodynamic compromise. Because nephrotic-range proteinuria was also present, a kidney biopsy was performed and showed mainly tubulointerstitial injury with pigmented casts and tubular atrophy, associated with focal segmental glomerulosclerosis. The patient was treated with intravenous hydration and gradual levothyroxine replacement, with clear clinical improvement and progressive normalization of laboratory abnormalities. This case highlights that severe hypothyroidism may rarely present with rhabdomyolysis and AKI. It also underlines the importance of considering thyroid dysfunction in patients with unexplained rhabdomyolysis, especially when the clinical picture is not very suggestive, since early treatment can lead to a favorable outcome.

Advanced HIV infection is associated with profound immunosuppression, predisposing patients to opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) and Mycobacterium avium complex (MAC). PJP can cause severe respiratory disease, including acute respiratory distress syndrome (ARDS), while disseminated MAC may contribute to systemic illness and pulmonary complications. Concurrent infection with both pathogens is uncommon but may precipitate severe pulmonary failure. A man in his 40s presented with unintentional weight loss, fatigue, oral thrush, and progressive dyspnea. On arrival, oxygen saturation was 86% on room air, requiring high-flow nasal cannula. Laboratory evaluation revealed profound immunosuppression (CD4 7 cells/mm[3], HIV RNA 123,000 copies/mL) and elevated β-D-glucan (>700 pg/mL). Chest CT demonstrated diffuse bilateral ground-glass opacities. He was initially treated empirically with broad-spectrum antibiotics (piperacillin-tazobactam and linezolid) and subsequently started on trimethoprim-sulfamethoxazole and corticosteroids for PJP. Despite supportive measures, the patient's respiratory status deteriorated, requiring intubation. Sputum cultures grew MAC, prompting initiation of azithromycin, rifampin, and ethambutol. The patient developed disseminated intravascular coagulation, acute tubular necrosis requiring daily hemodialysis, and septic shock requiring dual vasopressors. He was not a candidate for ECMO due to multi-organ failure in the context of advanced AIDS, and his prognosis remained guarded. This case highlights the rapid progression and complexity of opportunistic infections in advanced AIDS. Extensive diagnostic evaluation, early recognition of co-infections, and aggressive multidisciplinary management are essential, though outcomes may remain poor in patients with profound immunosuppression and multi-organ failure.

Formic acid is widely used in rubber latex coagulation, especially in semiurban and rural industrial settings. Its unregulated handling poses significant occupational health hazards. The objectives of the case series are to document the clinical, toxicological, and autopsy findings in six fatal cases of formic acid poisoning among rubber industry workers in Tripura, India. To document the clinical, toxicological, and autopsy findings in six fatal cases of formic acid poisoning among rubber industry workers in Tripura, India. This retrospective case series analyzed clinical records, autopsy findings, histopathology, and toxicology reports of six deceased individuals exposed to formic acid through ingestion or inhalation. All victims were rubber factory or plantation workers; five deaths were suicidal and one accidental. Common features included metabolic acidosis, gastrointestinal corrosion, pulmonary edema, and multi-organ failure. Histopathology revealed acute tubular necrosis, gastric mucosal necrosis, and alveolar edema. Toxicology confirmed lethal levels of formic acid. These cases highlight critical gaps in occupational safety, chemical handling practices, and mental health support in industrial environments handling corrosive agents like formic acid.

Oropouche virus (OROV) is an emerging orthobunyavirus that causes increasingly severe and deadly disease in Brazil. However, coinfection with influenza A(H1N1)pdm09 has not been previously described in the published literature, to our knowledge. We report the first documented fatal case of OROV and influenza A(H1N1)pdm09 coinfection in a previously healthy 16-year-old female from rural Maranhão, Brazil. The patient presented with dyspnea, odynophagia, and hemoptysis and deteriorated rapidly, requiring orotracheal intubation on day three of illness due to massive endobronchial hemorrhage, followed by fatal hemodynamic collapse. Autopsy revealed bilateral serosanguineous pleural effusion, diffuse alveolar hemorrhage, pericardial petechiae, acute tubular necrosis, and cerebral edema with tonsillar herniation. Real-time reverse-transcriptase polymerase chain reaction confirmed OROV in lung, liver, spleen, and lymph node tissues, and influenza A(H1N1)pdm09 in both nasal swab and lung tissue; all other arboviruses and respiratory pathogens tested negative. The histopathological findings provide, to our knowledge, the first histopathological characterization of OROV-associated microvascular injury and suggest synergistic thromboinflammatory pathways with influenza A. This case broadens the recognized clinical spectrum of OROV and highlights the need for systematic coinfection screening and coagulation monitoring in severe arboviral presentations, even in young patients without comorbidities.

BackgroundCryoablation is a well-established intervention for various pathologies. Cryoablation has been investigated as an alternative for cholecystitis in poor surgical candidates and as an adjunct to resection for invasive gallbladder cancer (GBC).MethodsA systematic search was performed in PubMed and Embase to identify studies investigating cryoablation in cholecystitis and GBC. Pooled overall (OS) and disease-free survival (DFS) analysis was conducted for the GBC population.ResultsFour studies in patients with cholecystitis (n = 29, mean age: 63.5 ± 16.8 years; 69% males) used 1-2 freeze cycles, and between 1 and 7 probes. The mean duration of cholecystostomy in place prior to cryoablation was 73.7 ± 37.1 days. Average hospital stay was 3.9 ± 7.5 days. At a follow-up of 15.6 ± 7.7 months, the efficacy of cryoablation varied between 86% and 100%. Complications included infection (6.9%), scrotal edema (3.4%), transient biliary obstruction (3.4%), anaphylaxis/death (3.4%), and hemorrhage/acute tubular necrosis (3.4%). In patients with GBC (n = 12, mean age: 57.9 ± 5.6 years), all four studies used one probe and most studies used 2 freeze cycles. At a follow-up of 13.1 ± 11.1 months, four patients (33.3%) with GBC had complications including pulmonary embolism, pleural effusion, exacerbation of congestive heart failure, and one biliary stricture, while one patient died at 3 months after the procedure. Gallbladder cancer recurred in 36.3% with median DFS of 10 (4-17) months. The OS was 88.8% at 6 months and 83.3% at 1-year post-procedure.ConclusionCryoablation is a technically feasible, definitive treatment option for poor surgical candidates with cholecystitis, targeting the same patient population typically selected for percutaneous cholecystostomy placement. Cryoablation is an experimental adjunct in GBC. Current evidence is limited, based on retrospective data and a very limited number of patients. Further prospective studies are needed to validate its efficacy and improve its safety in high-risk patients.

Acute kidney injury (AKI) is a common complication with poor clinical outcomes, and patients with high body mass index (BMI) are particularly vulnerable, especially after major surgical procedures, though the underlying mechanisms remain unclear. In this study, we used a Western diet (WD)-induced obesity model to examine how obesity influences Ischemia-reperfusion injury (IRI)-induced AKI and to explore the mechanisms involved. We found that obesity alone did not cause renal damage in healthy mice but markedly worsened kidney injury following IRI. RNA sequencing and bioinformatic analyses identified upregulation of hexokinase-2 as a key mediator of this effect. Notably, pharmacologic inhibition of hexokinase-2 restored metabolic balance in cultured human proximal tubule epithelial cells and alleviated renal injury in obese mice with AKI. Furthermore, clinical data showed that higher BMI and increased hexokinase-2 expression were associated with more severe tubular injury in patients with acute tubular necrosis. These findings demonstrate that obesity aggravates AKI through hexokinase-2-mediated metabolic reprogramming and suggest that targeting hexokinase-2 could be a promising therapeutic strategy for obese individuals at risk of AKI.

Ischemia-reperfusion injury (IRI) is a major driver of acute kidney injury and development of chronic kidney disease. Although complement activation worsens IRI, the roles of upstream (C3) versus downstream (C5) components remain unclear. Renal IRI was surgically induced in C3 knockout (C3[-]/[-]) and C5 knockout (C5[-]/[-]) Lewis rats, and the renal function as well as histopathology were systematically assessed. Further, quantitative proteomics coupled with pathway enrichment analysis was performed to define complement-dependent mechanisms. C3 and C5 deficiency conferred strong protection against renal IRI with improved renal function, reduced tubular necrosis, and lower expression of injury markers (KIM-1, NGAL). Post-IRI, C3[-/-] enhanced mitochondrial, metabolic, and purine pathways while suppressing immune and extra-cellular matrix programs. C5[-/-] affected extracellular matrix remodeling and structural pathways with modest immune suppression. We demonstrate for the first time that upstream C3[-/-] impacts a diverse range of renal injury and repair mechanisms compared to C5[-/-] alone, although both interventions successfully reduced IRI-mediated injury. Together, these findings highlight strategies for future complement-based therapies targeting the upstream or downstream cascade.

Renal arcuate vein thrombosis (RAVT) is a rare and often underrecognized cause of acute kidney injury (AKI) that typically requires renal biopsy for diagnosis. We report a 29-year-old man who developed AKI following heavy alcohol intake, an upper respiratory tract infection, and exposure to multiple medications including repeated nonsteroidal anti-inflammatory drugs and traditional Chinese patent medicines. Laboratory tests showed mild proteinuria without hematuria and negative autoimmune serology, with normal renal imaging. Renal biopsy revealed acute tubular injury and thrombus-like material within arcuate veins, accompanied by mild medullary hemorrhage and focal vascular necrosis, findings suggestive of arcuate venous thrombosis. Renal function recovered completely after supportive therapy within eight days.This case highlights that an arcuate venous lesion suggestive of thrombosis may be an underrecognized finding in patients with multifactorial, biopsy-proven AKI, even when the clinical presentation and imaging findings are nonspecific. Awareness of this possibility may broaden the differential diagnosis in selected patients with unexplained or disproportionate AKI and multiple renal risk factors, and kidney biopsy may help identify otherwise unrecognized vascular involvement.

Cisplatin remains a major cause of acute kidney injury (AKI) and effective therapeutic strategies are still lacking. Cytochrome P450 2E1 (CYP2E1), a phase I metabolic enzyme, has been increasingly implicated in inflammatory disorders. This study aimed to investigate the therapeutic potential and underlying mechanisms of a novel CYP2E1 inhibitor, Q11, in cisplatin-induced AKI. The role of CYP2E1 in AKI was assessed using Cyp2e1 knockout rats, and the protective effects of Q11 were evaluated in a mouse model. Further mechanistic insights were gained through transcriptomic analysis and experiments in renal tubular epithelial cells. The results showed that CYP2E1 expression and enzymatic activity were significantly elevated in AKI animals. Knockout of Cyp2e1 markedly attenuated renal dysfunction and inflammation. Treatment with Q11 similarly improved survival, reduced serum creatinine and blood urea nitrogen levels, and alleviated renal histopathological damage in cisplatin-treated mice. Mechanistically, Q11 suppressed oxidative stress by reducing reactive oxygen species (ROS) and increasing glutathione levels, and also downregulated pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Transcriptomic and western blot analyses revealed that Q11 inhibited the nuclear factor kappa B (NF-κB) signaling pathway and restored mitochondrial function. In vitro studies further demonstrated that Q11 reduced CYP2E1 expression, improved mitochondrial membrane potential, and decreased apoptosis in human kidney-2 cells (HK-2) and mouse renal tubular epithelial cells (mRTEC). In conclusion, CYP2E1 plays a pivotal role in cisplatin-induced AKI, and the novel inhibitor Q11 exerts renoprotective effects by mitigating mitochondrial dysfunction and suppressing NF-κB-mediated inflammation.

Diabetes is often assumed to cause chronic kidney disease (CKD) in patients with diabetes, though non-diabetic pathology may coexist. We reviewed 84 patients with diabetes who underwent native kidney biopsy (2017-2023). Indications included active urinary sediment, nephrotic-range proteinuria and rapid renal decline. Non-diabetic pathology was found in 49% and mixed lesions in 21%, mainly IgA nephropathy, acute tubular necrosis and interstitial nephritis. Biopsy altered management in 23% of cases. These findings support the value of biopsy in patients with diabetes.

Ferroptosis, a modality of regulated necrosis caused by iron-dependent lipid peroxidation, has emerged as a key contributor to the pathogenesis of acute tubular necrosis (ATN) - especially in the context of solid organ transplantation. While recent studies have identified hormones as extracellular signals that modulate cellular susceptibility to ferroptosis, their pathophysiological relevance in vivo remains incompletely defined. Here, we investigated the role of dexamethasone, a potent synthetic glucocorticoid previously reported to sensitize cells to ferroptosis, in the context of renal tubular injury. Unexpectedly, we observed a biphasic effect: early sensitization to ferroptosis induced by glutathione depletion was subsequently counteracted by a marked increase in ferroptosis resistance. Mechanistically, we found that dexamethasone reduced availability of ferrous iron via effects of the glucocorticoid receptor 1 (GR1), which also resulted in attenuated renal tubular injury. However, this cytoprotective effect did not translate into improved renal function, as dexamethasone exerted additional ferroptosis-independent effects on innate immune cell recruitment to injured kidneys. Collectively, our findings highlight the highly dynamic nature of the ferroptotic process in which modulatory signals can exert temporally opposing effects. Moreover, they underscore the complex interplay between regulated cell death and innate immune responses in shaping necroinflammation in disease trajectories.