Incidence and risk factors of peri-operative stroke in major non-cardiovascular, non-neurologic surgery-A retrospective register-based cohort study.

BACKGROUND: Peri-operative stroke is a rare but serious surgical complication. Both overt and covert stroke, occurring in approximately 0.1% and 7% of cases, respectively, are associated with significant long-term effects and increased morbidity. METHODS: Retrospective register data for patients >18 years old, presenting for major non-cardiovascular, non-neurosurgical and non-ambulatory surgical procedures at 23 hospitals in Sweden between 2007 and 2014 was collected and linked with various quality registers. The primary outcome was stroke within 30 days from surgery. Using multivariable logistic regression, significant independent risk factors influencing the primary outcome were identified and their adjusted odds ratios (ORs) were calculated. Mortality was assessed, along with the composite score of days alive and at home within 30 days after surgery (DAH 30). RESULTS: In total, 318,017 patients were included, with 687 (0.22%) suffering a stroke within 30 days of surgery. The strongest significant risk factors included: increasing ASA-class (OR [95% confidence interval, CI]: 2.23 [1.53-3.36], 3.91 [2.68-5.93] and 7.82 [5.03-12.5] for ASA 2, 3 and 4, respectively) and age (OR [95% CI]: 4.47 [2.21-10.3], 9.9 [5.15-22.1], 16.3 [8.48-36.5] and 21 [10.6-48.1], for age 45-59, 60-74, 75-89 and >90, respectively), along with non-elective procedures, male gender and a history of cerebrovascular disease (OR [95%]: 2.72 [2.25-3.27]). Mortality was increased and DAH 30 was reduced in patients suffering a stroke. CONCLUSIONS: Increasing ASA-class and age was clearly associated with an increased risk of peri-operative stroke, which in turn was associated with increased mortality and poorer outcome. Detailed pre-operative risk stratification and individualised peri-operative management could potentially improve patient-centred outcomes and, in turn, have positive implications for public health.

A vanguard randomised feasibility trial comparing three regimens of peri-operative oxygen therapy on recovery after major surgery.

International recommendations encourage liberal administration of oxygen to patients having surgery under general anaesthesia, ostensibly to reduce surgical site infection. However, the optimal oxygen regimen to minimise postoperative complications and enhance recovery from surgery remains uncertain. The hospital operating theatre randomised oxygen (HOT-ROX) trial is a multicentre, patient- and assessor-blinded, parallel-group, randomised clinical trial designed to assess the effect of a restricted, standard care, or liberal peri-operative oxygen therapy regimen on days alive and at home after surgery in adults undergoing prolonged non-cardiac surgery under general anaesthesia. Here, we report the findings of the internal vanguard feasibility phase of the trial undertaken in four large metropolitan hospitals in Australia and New Zealand that included the first 210 patients of a planned overall 2640 trial sample, with eight pre-specified endpoints evaluating protocol implementation and safety. We screened a total of 956 participants between 1 September 2019 and 26 January 2021, with data from 210 participants included in the analysis. Median (IQR [range]) time-weighted average intra-operative Fi O2 was 0.30 (0.26-0.35 [0.20-0.59]) and 0.47 (0.44-0.51 [0.37-0.68]) for restricted and standard care, respectively (mean difference (95%CI) 0.17 (0.14-0.20), p < 0.001). Median time-weighted average intra-operative Fi O2 was 0.83 (0.80-0.85 [0.70-0.91]) for liberal oxygen therapy (mean difference (95%CI) compared with standard care 0.36 (0.33-0.39), p < 0.001). All feasibility endpoints were met. There were no significant patient adverse events. These data support the feasibility of proceeding with the HOT-ROX trial without major protocol modifications.

Concomitant Lung and Kidney Disorders in Critically Ill Patients: Core Curriculum 2022.

The lungs and kidneys are cooperative and interdependent organs that secure the homeostasis of the body. Volume and acid-base disorders sit at the nexus between these two systems. However, lung-kidney interactions affect the management of many other conditions, especially among critically ill patients. Therefore, management of one system cannot proceed without a thorough understanding of the physiology of the other. This installment of AJKD's Core Curriculum in Nephrology discusses the complex decision-making required in treating concomitant respiratory and kidney disorders. We cover systemic diseases of the pulmonary and glomerular capillaries, acute decompensated heart failure, management of acid-base disorders in acute respiratory distress syndrome and chronic obstructive pulmonary disease, and venous thromboembolism. Through a case-based approach, we weigh the factors affecting the risks and benefits of therapies to enable the reader to individualize treatment decisions in these challenging scenarios.

A single amino acid substitution uncouples catalysis and allostery in an essential biosynthetic enzyme in Mycobacterium tuberculosis.

Allostery exploits the conformational dynamics of enzymes by triggering a shift in population ensembles toward functionally distinct conformational or dynamic states. Allostery extensively regulates the activities of key enzymes within biosynthetic pathways to meet metabolic demand for their end products. Here, we have examined a critical enzyme, 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS), at the gateway to aromatic amino acid biosynthesis in Mycobacterium tuberculosis, which shows extremely complex dynamic allostery: three distinct aromatic amino acids jointly communicate occupancy to the active site via subtle changes in dynamics, enabling exquisite fine-tuning of delivery of these essential metabolites. Furthermore, this allosteric mechanism is co-opted by pathway branchpoint enzyme chorismate mutase upon complex formation. In this study, using statistical coupling analysis, site-directed mutagenesis, isothermal calorimetry, small-angle X-ray scattering, and X-ray crystallography analyses, we have pinpointed a critical node within the complex dynamic communication network responsible for this sophisticated allosteric machinery. Through a facile Gly to Pro substitution, we have altered backbone dynamics, completely severing the allosteric signal yet remarkably, generating a nonallosteric enzyme that retains full catalytic activity. We also identified a second residue of prime importance to the inter-enzyme communication with chorismate mutase. Our results reveal that highly complex dynamic allostery is surprisingly vulnerable and provide further insights into the intimate link between catalysis and allostery.

Quality of recovery after total hip and knee arthroplasty in South Africa: a national prospective observational cohort study.

BACKGROUND: Encouraged by the widespread adoption of enhanced recovery protocols (ERPs) for elective total hip and knee arthroplasty (THA/TKA) in high-income countries, our nationwide multidisciplinary research group first performed a Delphi study to establish the framework for a unified ERP for THA/TKA in South Africa. The objectives of this second phase of changing practice were to document quality of patient recovery, record patient characteristics and audit standard perioperative practice. METHODS: From May to December 2018, nine South African public hospitals conducted a 10-week prospective observational study of patients undergoing THA/TKA. The primary outcome was 'days alive and at home up to 30 days after surgery' (DAH30) as a patient-centred measure of quality of recovery incorporating early death, hospital length of stay (LOS), discharge destination and readmission during the first 30 days after surgery. Preoperative patient characteristics and perioperative care were documented to audit practice. RESULTS: Twenty-one (10.1%) out of 207 enrolled patients had their surgery cancelled or postponed resulting in 186 study patients. No fatalities were recorded, median LOS was 4 (inter-quartile-range (IQR), 3-5) days and 30-day readmission rate was 3.8%, leading to a median DAH30 of 26 (25-27) days. Forty patients (21.5%) had pre-existing anaemia and 24 (12.9%) were morbidly obese. In the preoperative period, standard care involved assessment in an optimisation clinic, multidisciplinary education and full-body antiseptic wash for 67 (36.2%), 74 (40.0%) and 55 (30.1%) patients, respectively. On the first postoperative day, out-of-bed mobilisation was achieved by 69 (38.1%) patients while multimodal analgesic regimens (paracetamol and Non-Steroid-Anti-Inflammatory-Drugs) were administered to 29 patients (16.0%). CONCLUSION: Quality of recovery measured by a median DAH30 of 26 days justifies performance of THA/TKA in South African public hospitals. That said, perioperative practice, including optimisation of modifiable risk factors, lacked standardisation suggesting that quality of patient care and postoperative recovery may improve with implementation of ERP principles. Notwithstanding the limited resources available, we anticipate that a change of practice for THA/TKA is feasible if 'buy-in' from the involved multidisciplinary units is obtained in the next phase of our nationwide ERP initiative. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03540667 ).

Sevoflurane induced diffuse alveolar haemorrhage in a young patient after orthopedic surgery: A case report.

We present a very rare case of Sevoflurane Induced Diffuse Alveolar Haemorrhage in a young male patient with a closed tibial fracture after direct trauma to the right cruris. The patient was operated for tibial fracture, but diffuse alveolar haemorrhage developed after sevoflurane inhalation in the postoperative period following general anesthesia. Diffuse alveolar haemorrhage (DAH) is associated with inhalation injury from halogenated gases and reported as a unique entity in the literature that practicing clinicians should be aware of and consider in post-operative cases of acute respiratory distress. As DAH usually presents with symptoms the presence of hemoptysis, anemia, dyspnoea and radiological alveolar infiltrates, rapid detection of the aetiology and initiation of cause-directed treatment are of great importance on survival.

Etiology and outcome of pulmonary renal syndrome: Retrospective study from a tertiary care hospitaln.

To determine the aetiology, clinical characteristics and outcome of patients admitted with pulmonary renal syndrome (PRS). This retrospective analysis was conducted at Aga Khan University Hospital from 2011 to 2015. A total of 17 adult patients admitted with PRS were included and followed up for a period of one year for the outcome of PRS as recovery, dialysis dependency or death. Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) was found to be the single most frequent cause in 13 (76.4%) patients. The c o mm o n e s t c a u s e o f A AV w a s fo u n d t o b e Granulomatous polyangitis (GPA) in 10 (58.8%) followed by Microscopic angitis in 3 (17.6%) patients. Around 12 (70.5%) patients survived, 11 (64.7%) recovered while 1 patient remained dialysis dependent. Mortality rate was 29.4% and all these patients had severe alveolar haemorrhages. None of our patient died or relapsed during one year follow up.

Structural analysis of substrate-mimicking inhibitors in complex with Neisseria meningitidis 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase - The importance of accommodating the active site water.

3-Deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyses the first committed step of the shikimate pathway, which produces the aromatic amino acids as well as many other aromatic metabolites. DAH7PS catalyses an aldol-like reaction between phosphoenolpyruvate and erythrose 4-phosphate. Three phosphoenolpyruvate mimics, (R)-phospholactate, (S)-phospholactate and vinyl phosphonate [(E)-2-methyl-3-phosphonoacrylate], were found to competitively inhibit DAH7PS from Neisseria meningitidis, which is the pathogen responsible for bacterial meningitis. The most potent inhibitor was the vinyl phosphonate with a Ki value of 3.9±0.4µM. We report for the first time crystal structures of these compounds bound in the active site of a DAH7PS enzyme which reveals that the inhibitors bind to the active site of the enzyme in binding modes that mimic those of the predicted oxocarbenium and tetrahedral intermediates of the enzyme-catalysed reaction. Furthermore, the inhibitors accommodate the binding of a key active site water molecule. Together, these observations provide strong evidence that this active site water participates directly in the DAH7PS reaction, enabling the facial selectivity of the enzyme-catalysed reaction sequence to be delineated.

Successful rituximab therapy in adult-onset IgA vasculitis with diffuse alveolar hemorrhage and renal failure: a case report.

Background: Immunoglobulin A vasculitis (IgAV) is a rare condition that most commonly presents during childhood. Patients with adult-onset IgAV are more likely to exhibit severe symptoms at presentation with worse renal outcomes. Pulmonary manifestations of adult-onset IgAV have been described rarely in the literature and often indicate higher morbidity and mortality. Given the rarity of alveolar hemorrhage in IgAV, the literature describing the clinical entity and offering management recommendations is insufficient. Case Description: We describe a patient with known adult-onset IgAV who presented with one month of abdominal pain, bloody stools, new skin lesions, and progressive shortness of breath. She developed rapidly worsening hypoxic respiratory failure associated with a hemoglobin drop and diffuse pulmonary infiltrates on imaging. Bronchoscopy demonstrated progressively hemorrhagic effluent on bronchoalveolar lavage (BAL) consistent with a diagnosis of diffuse alveolar hemorrhage (DAH). She developed acute renal failure requiring the initiation of emergent renal replacement therapy. Given concomitant DAH and acute renal failure, methylprednisolone and rituximab (RTX) therapy were initiated. With this treatment regimen, she exhibited marked improvement in respiratory function and complete renal recovery. Conclusions: This case highlights the importance of considering DAH as a rare and life-threatening pulmonary manifestation of adult-onset IgAV. Our case demonstrates the novel and successful use of RTX in combination with steroids to treat a patient with adult-onset IgAV presenting with concomitant DAH and renal failure.

Recurrent diffuse alveolar hemorrhage and extracorporeal membrane oxygenation utilization in a hematopoietic stem cell transplant patient with Hunter's syndrome.

We describe the natural history of a three-month-old patient with Hunter Syndrome with hematopoietic stem cell transplant (HSCT) who developed recurrent diffuse alveolar hemorrhage (DAH) requiring extracorporeal membrane oxygenation (ECMO). The patient underwent HSCT with several complications, including veno-occlusive disease and DAH. He was managed with ECMO. Unfortunately, despite initial success he developed recurrent DAH and ultimately died. This is a novel report of this severe adverse event requiring ECMO following the use of HSCT in this rare patient population. We share the clinical strategies employed to address the complications associated with HSCT and the progression of his disease over his hospitalization.

Intrapulmonary administration of recombinant activated factor VII in pediatric, adolescent, and young adult oncology and hematopoietic cell transplant patients with pulmonary hemorrhage.

Introduction: Diffuse alveolar hemorrhage (DAH) is a devastating disease process with 50-100% mortality in oncology and hematopoietic cell transplant (HCT) recipients. High concentrations of tissue factors have been demonstrated in the alveolar wall in acute respiratory distress syndrome and DAH, along with elevated levels of tissue factor pathway inhibitors. Activated recombinant factor VII (rFVIIa) activates the tissue factor pathway, successfully overcoming the tissue factor pathway inhibitor (TFPI) inhibition of activation of Factor X. Intrapulmonary administration (IP) of rFVIIa in DAH is described in small case series with successful hemostasis and minimal complications. Methods: We completed a single center retrospective descriptive study of treatment with rFVIIa and outcomes in pediatric oncology and HCT patients with pulmonary hemorrhage at a quaternary hematology/oncology hospital between 2011 and 2019. We aimed to assess the safety and survival of patients with pulmonary hemorrhage who received of IP rFVIIa. Results: We identified 31 patients with pulmonary hemorrhage requiring ICU care. Thirteen patients received intrapulmonary rFVIIa, while eighteen patients did not. Overall, 13 of 31 patients (41.9%) survived ICU discharge. ICU survival (n=6) amongst those in the IP rFVIIa group was 46.2% compared to 38.9% (n=7) in those who did not receive IP therapy (p=0.69). Hospital survival was 46.2% in the IP group and 27.8% in the non-IP group (p=0.45). There were no adverse events noted from use of IP FVIIa. Conclusions: Intrapulmonary rFVIIa can be safely administered in pediatric oncology patients with pulmonary hemorrhage and should be considered a viable treatment option for these patients.

Extensive Thrombosis in Catastrophic Antiphospholipid Syndrome in a Newly Diagnosed Systemic Lupus Erythematosus: A Case Report.

In this case report, we present the development of catastrophic antiphospholipid syndrome (CAPS), a rare and potentially fatal consequence of systemic lupus erythematosus (SLE), in a 33-year-old Micronesian woman. CAPS is characterized by extensive arterial thrombosis and multiorgan failure. The patient first showed signs of neuropsychiatric symptoms, brain infarctions on imaging, and severe hypoxic respiratory failure brought into the hospital by diffuse alveolar hemorrhage (DAH) along with lupus nephritis (LN). Blood urea nitrogen (BUN) and creatinine (Cr) were progressively elevated to 102/4.1 mg/dL, respectively. A urinalysis revealed microscopic hematuria and proteinuria with a urine protein/creatinine ratio of 6052 mg/g. She was also found to have had microangiopathic hemolytic anemia (MAHA) and severe venous thrombosis, both of which were indicative of CAPS. An aggressive approach, including immunosuppressive medication, therapeutic plasma exchange, and anticoagulation, had positive results, including renal recovery and the cessation of thrombotic episodes. This instance highlights how crucial it is to identify CAPS patients early and take appropriate action to improve patient outcomes for this difficult and sometimes deadly disorder.

A Case Report of Refractory Diffuse Alveolar Hemorrhage as a Complication of Antiphospholipid Syndrome and Review of Its Management.

Diffuse alveolar hemorrhage is a rare complication of antiphospholipid syndrome with high mortality rates. Early diagnosis and treatment with steroids and immunosuppressive agents, along with the achievement of hemostasis and hemodynamic stability, is critical to improving outcomes. This case demonstrates the complexity of managing refractory diffuse alveolar hemorrhage in a 48-year-old woman with antiphospholipid syndrome requiring treatment with high-dose corticosteroids, rituximab, and cyclophosphamide.

A Rare Case of Diffuse Alveolar Hemorrhage Caused by Fentanyl Inhalation.

Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening pulmonary disorder characterized by blood accumulation in alveolar spaces, often associated with autoimmune diseases and infections. Drug-induced causes of DAH, including inhalation of substances like fentanyl, are emerging concerns. A 40-year-old male with bipolar disorder and polysubstance abuse presented with altered mental status and hemoptysis after inhaling an unknown substance. Physical examination revealed respiratory distress, pinpoint pupils, and severe hypoxemia. Naloxone administration improved his condition. The workup showed negative infection markers, positive fentanyl-specific urine test, and diffuse bilateral opacities on imaging. Bronchoalveolar lavage confirmed DAH with >20% hemosiderin-laden macrophages. Steroid treatment resulted in marked improvement. Drug-induced DAH, such as fentanyl inhalation, should be considered in patients with altered mental status and pulmonary symptoms following substance use. Comprehensive evaluation and targeted treatment are crucial for optimal outcomes.

eNAMPT/TLR4 inflammatory cascade activation is a key contributor to SLE Lung vasculitis and alveolar hemorrhage.

Rationale: Effective therapies to reduce the severity and high mortality of pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) is a serious unmet need. We explored whether biologic neutralization of eNAMPT (extracellular nicotinamide phosphoribosyl-transferase), a novel DAMP and Toll-like receptor 4 ligand, represents a viable therapeutic strategy in lupus vasculitis. Methods: Serum was collected from SLE subjects (n = 37) for eNAMPT protein measurements. In the preclinical pristane-induced murine model of lung vasculitis/hemorrhage, C57BL/6 J mice (n = 5-10/group) were treated with PBS, IgG (1 mg/kg), or the eNAMPT-neutralizing ALT-100 mAb (1 mg/kg, IP or subcutaneously (SQ). Lung injury evaluation (Day 10) included histology/immuno-histochemistry, BAL protein/cellularity, tissue biochemistry, RNA sequencing, and plasma biomarker assessment. Results: SLE subjects showed highly significant increases in blood NAMPT mRNA expression and eNAMPT protein levels compared to healthy controls. Preclinical pristane-exposed mice studies showed significantly increased NAMPT lung tissue expression and increased plasma eNAMPT levels accompanied by marked increases in alveolar hemorrhage and lung inflammation (BAL protein, PMNs, activated monocytes). In contrast, ALT-100 mAb-treated mice showed significant attenuation of inflammatory lung injury, alveolar hemorrhage, BAL protein, tissue leukocytes, and plasma inflammatory cytokines (eNAMPT, IL-6, IL-8). Lung RNA sequencing showed pristane-induced activation of inflammatory genes/pathways including NFkB, cytokine/chemokine, IL-1ß, and MMP signaling pathways, each rectified in ALT-100 mAb-treated mice. Conclusions: These findings highlight the role of eNAMPT/TLR4-mediated inflammatory signaling in the pathobiology of SLE pulmonary vasculitis and alveolar hemorrhage. Biologic neutralization of this novel DAMP appears to serve as a viable strategy to reduce the severity of SLE lung vasculitis.

The burden of malaria in sub-Saharan Africa and its association with development assistance for health and governance: An exploration of the GBD 2019 study.

Even with a reduced burden of malaria in sub-Saharan Africa (SSA), differences remain in the rate of change among countries and sub-regions. We used data from the Global Burden of Disease Study 2019 to establish the relationship between Development Assistance for Health (DAH) and governance and trends in malaria burden in SSA. The trend was estimated using the Joinpoint regression program and the Institute of Health Metrics and Evaluation's DAH database, and World Bank Governance Indicators to analyze the DAH and governance respectively from 2000 to 2017 and used two-way fixed effects to establish their association with the trend in the period. The findings showed decreases in SSA's age-standardised rates for disability-adjusted life years (ASDR) (-47% (95% uncertainty interval (UI) -69% to -14%)), deaths (-38% (95% UI -65% to -3%)), incidence (-35% (95% UI -44% to -25%)), and prevalence (-34% (95% UI -43% to -24%)). Decreases in ASDR were associated with increases in DAH (ß -134.18, standard error (SE) 27.26) and governance scores (ß -246.19, SE 39.13). The association between reductions in malaria burden and increases in DAH and in governance scores shows the need for accelerated funding of malaria programs and advocacy for better disease governance in malaria-endemic countries.Abbreviations: APC: Annual percentage change; ASDR: Age-standardised disability-adjusted life-year rate; ASIR: Age-standardised incidence rate; ASIR: Age-standardised incidence rate; ASMR: Age-standardised mortality rate; CSSA: Central sub-Saharan Africa; DAH: Development Assistance for Health; DALYs: Disability-adjusted life years; ESSA: Eastern sub-Saharan Africa; GBD: Global burden of disease; GHDx Global Health Data Exchange; IHME: Institute of Health Metrics and Evaluation; SDGs: Sustainable Development Goals; SSA: Sub-Saharan Africa; SSSA: Southern sub-Saharan Africa; UNSD: United Nations Statistics Division; USD: United States dollars; WGI: World Bank Governance Indicators; WHO: World Health Organization; WSSA: Western sub-Saharan Africa.

Clinical Dilemmas in Immune Thrombocytopenic Purpura With Diffuse Alveolar Hemorrhage: Diagnosis, Treatment, and Outcomes.

This report elucidates a unique case of a 39-year-old female with immune thrombocytopenic purpura (ITP) who developed a rare and severe complication: diffuse alveolar hemorrhage (DAH). Despite initial treatments for ITP, the patient experienced fluctuating platelet (PLT) counts and shortness of breath, which were later identified as symptoms of DAH. An urgent splenectomy improved the patient's platelet counts and overall condition. This case underscores the imperative to recognize DAH as a possible ITP complication, requiring clinicians' vigilance for prompt diagnosis and intervention. The intricate nature of ITP in adults necessitates individualized, patient-centered treatment approaches to enhance outcomes. This report provides invaluable insights into the clinical understanding and management of ITP and its complications through detailed analysis and documentation of the patient's treatment journey.

A Rare Case of Diffuse Alveolar Hemorrhage Caused by Fentanyl-Laced Marijuana.

Synthetic fentanyl adulteration has become a significant threat to public safety. It is commonly mixed into other drugs of abuse to lower costs and increase its addictive potential. Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication associated with the use of fentanyl-laced products. Given the current trend, we anticipate an increase in the incidence of DAH. It is crucial to recognize and treat DAH early in its course for better outcomes. We present a case of DAH due to an overdose of marijuana laced with fentanyl, manifesting as hemoptysis, and provide a review of the current literature on the topic.

Pulmonary Manifestations and Vascular Changes in Pediatric Transplantation-Associated Thrombotic Microangiopathy.

Although transplant-associated thrombotic microangiopathy (TA-TMA) commonly complicates pediatric hematopoietic cellular therapy (HCT), pulmonary manifestations and histology of TA-TMA (pTA-TMA) are rarely reported, with scant data available on timing, risk factors, pathogenesis, and outcomes. Pulmonary hypertension (PH) and diffuse alveolar hemorrhage (DAH) are recognized manifestations of pTA-TMA. The objective of this study was to characterize the pathologic findings, outcomes, and coincident diagnoses preceding biopsy-proven pTA-TMA. In Institutional Review Board- approved retrospective studies, available lung tissue was reviewed at 2 institutions between January 2016 and August 2021 to include those with pulmonary vascular pathology. Histologic features of pTA-TMA were present in 10 children with prior respiratory decline after an allogeneic HCT (allo-HCT; n = 9) or autologous HCT (n = 1). Pathologic lesions included muscular medialization, microthrombi, and red cell fragments, in addition to perivasculitis and intimal arteritis. Parenchymal findings included diffuse alveolar damage, organizing pneumonia, and plasmocytic infiltrates. Six children were clinically diagnosed with TA-TMA, and all were treated with eculizumab, at a median of 2.5 days after clinical diagnosis (range, 0 to 11 days). Four were identified postmortem. Coincident pulmonary infection was confirmed in 8 of the 10 patients. Five allo-HCT recipients (56%) experienced graft-versus-host disease (GVHD; 4 acute, 1 chronic) prior to the onset of respiratory symptoms. Two patients (20%) had clinically recognized DAH, although 9 (90%) had evidence of DAH on histology. Although all 10 patients underwent echocardiography at the time of symptom onset and 9 had serial echocardiograms, only 2 patients had PH detected. Treatments varied and included sildenafil (n = 3), steroids (n = 1), and eculizumab (n = 6). One patient was alive at the time of this report; the remaining 9 died, at a median of 52 days after onset of respiratory symptoms (range 4 to 440 days) and a median of 126 days post-HCT (range, 13 to 947 days). pTA-TMA is a heterogeneous histologic disease characterized by arteriolar inflammation, microthrombi, and often DAH. pTA-TMA presented with respiratory decline with systemic TA-TMA in all patients. Clinicians should maintain a high degree of suspicion for DAH in patients with TA-TMA and pulmonary symptoms. Coincident rates of GVHD and pulmonary infections were high, whereas the rate of PH identified by echocardiography was 20%. Outcomes were poor despite early use of eculizumab and other therapies. Our data merit consideration of pTA-TMA in patients with acute respiratory decline in the setting of systemic TA-TMA, GVHD, and infection. Investigation of additional therapies for pTA-TMA is needed as well. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Fat emboli-Related diffuse alveolar haemorrhage (FEDAH) an acronym to remember-Case series.

Fat embolism syndrome (FES) is a rare but potentially fatal complication of trauma or orthopaedic surgery, which presents predominantly with pulmonary symptoms. The rapid worsening respiratory failure in a previously normal orthopaedic surgery or trauma patients usually get evaluated for pulmonary embolism, fat-embolism-related acute respiratory distress or transfusion related acute lung injury. Orthopaedic surgeons and clinicians need to be aware of related entity termed 'Fat Embolism related Diffuse Alveolar Haemorrhage' (FEDAH). The clinical presentation in an orthopaedic surgery of trauma patient with FEDAH are haemoptysis, worsening type 1 respiratory failure and oxygen requirement, drop in haemoglobin levels with chest x-ray/computed tomography suggestive of Diffuse alveolar haemorrhage (DAH). Early bronchoscopy and bronchoalveolar lavage (BAL) confirmation of DAH, presence of BAL haemosiderophages and lipid-laden macrophages are the pointers in the early diagnosis of FEDAH. It needs a high clinical suspicion and interdepartmental collaborative measures. Timely referral from orthopaedic surgeons, early bronchoscopy and treatment with steroids is key in diagnosis and management.