Primary amebic meningoencephalitis: a review of Naegleria fowleri and analysis of successfully treated cases.

Primary amebic meningoencephalitis (PAM) is a necrotizing and hemorrhagic inflammation of the brain and meninges caused by Naegleria fowleri, a free-living thermophilic ameba of freshwater systems. PAM remains a neglected disease that disproportionately affects children in tropical and subtropical climates, with an estimated mortality rate of 95-98%. Due to anthropogenic climate change, the average temperature in the USA has increased by 0.72 to 1.06 °C in the last century, promoting the poleward spread of N. fowleri. PAM is often misdiagnosed as bacterial meningitis or viral encephalitis, which shortens the window for potentially life-saving treatment. Diagnosis relies on the patient's history of freshwater exposure and the physician's high index of suspicion, supported by cerebrospinal fluid studies. While no experimental trials have been conducted to assess the relative efficacy of treatment regimens, anti-amebic therapy with adjunctive neuroprotection is standard treatment in the USA. We performed a literature review and identified five patients from North America between 1962 and 2022 who survived PAM with various degrees of sequelae.

Intracardiac thrombosis and pulmonary thromboembolism during liver transplantation: A systematic review and meta-analysis.

Intracardiac thrombosis and/or pulmonary thromboembolism (ICT/PE) is a rare but devastating complication during liver transplantation. Its pathophysiology remains poorly understood, and successful treatment remains a challenge. This systematic review summarizes the available published clinical data regarding ICT/PE during liver transplantation. Databases were searched for all publications reporting on ICT/PE during liver transplantation. Data collected included its incidence, patient characteristics, the timing of diagnosis, treatment strategies, and patient outcomes. This review included 59 full-text citations. The point prevalence of ICT/PE was 1.42%. Thrombi were most often diagnosed during the neohepatic phase, particularly at allograft reperfusion. Intravenous heparin was effective in preventing early-stage thrombus from progressing further and restoring hemodynamics in 76.32% of patients it was utilized for; however, the addition of tissue plasminogen activator or sole use of tissue plasminogen activator offered diminishing returns. Despite all resuscitation efforts, the in-hospital mortality rate of an intraoperative ICT/PE was 40.42%, with nearly half of these patients dying intraoperatively. The results of our systematic review are an initial step for providing clinicians with data that can help identify higher-risk patients. The clinical implications of our results warrant the development of identification and management strategies for the timely and effective treatment of these tragic occurrences during liver transplantation.

Transfusion-Related Acute Lung Injury During Liver Transplantation: A Scoping Review.

Liver transplantation is associated with significant blood loss, often requiring massive blood product transfusion. Transfusion-related acute lung injury (TRALI) is a devastating cause of transfusion-related deaths. While reports have investigated the general incidence of TRALI, the incidence of TRALI specifically following transfusion during liver transplant remains unclear. This scoping review summarizes existing literature regarding TRALI during the liver transplantation perioperative period. Databases were searched for all articles and abstracts reporting on TRALI after liver transplantation. Data collected included number of patients studied, patient characteristics, incidences of TRALI, TRALI characteristics, and patient outcomes. The primary outcome investigated was the incidence of TRALI in the setting of liver transplantation. Thirteen full-text citations were included in this review. The incidence of TRALI post-liver transplant was 0.68% (65 of 9,554). Based on reported transfusion data, patients diagnosed with TRALI received an average of 10.92 ± 10.81 units of packed red blood cells (pRBC), 20.05 ± 15.72 units of fresh frozen plasma, and 5.75 ± 10.00 units of platelets. Common interventions following TRALI diagnosis included mechanical ventilation with positive end-expiratory pressure, inhaled high-flow oxygen, inhaled pulmonary vasodilator, and pharmacologic treatment using pressors or inotropes, corticosteroids, or diuretics. Based on reported mortality data, 26.67% of patients (12 of 45) diagnosed with TRALI died during the postoperative period. This scoping review underscores the importance of better understanding the incidence and presentation of TRALI after liver transplant surgery. The clinical implications of these results warrant the development of identification and management strategies for liver transplant patients at increased risk for developing TRALI.

Vasoplegic syndrome during heart transplantation: A systematic review and meta-analysis.

BACKGROUND: Vasoplegic syndrome (VS) is a common occurrence during heart transplantation (HT). It currently lacks a uniform definition between transplant centers, and its pathophysiology and treatment remain enigmatic. This systematic review summarizes the available published clinical data regarding VS during HT. METHODS: We searched databases for all published reports on VS during HT. Data collected included the incidence of VS in the HT population, patient and intraoperative characteristics, and postoperative outcomes. RESULTS: Twenty-two publications were included in this review. The prevalence of VS during HT was 28.72% (95% confidence interval: 27.37%, 30.10%). Factors associated with VS included male sex, higher body mass index, hypothyroidism, pre-HT left ventricular assist device or venoarterial extracorporeal membrane oxygenation (VA-ECMO), pre-HT calcium channel blocker or amiodarone usage, longer cardiopulmonary bypass time, and higher blood product transfusion requirement. Patients who developed VS were more likely to require postoperative VA-ECMO support, renal replacement therapy, reoperation for bleeding, longer mechanical ventilation, and a greater 30-day and 1-year mortality. CONCLUSIONS: The results of our systematic review are an initial step for providing clinicians with data that can help identify high-risk patients and avenues for potential risk mitigation. Establishing guidelines that officially define VS will aid in the precise diagnosis of these patients during HT and guide treatment. Future studies of treatment strategies for refractory VS are needed in this high-risk patient population.

Dr. Allen Oldfather Whipple (1881-1963): Namesake of the pancreaticoduodenectomy.

Allen O. Whipple was an American surgeon who popularized the pancreaticoduodenectomy (Whipple procedure) for periampullary cancer, which remains the gold standard for pancreatic tumor resections. Whipple was educated at Princeton University (B.S., 1904) and Columbia University College of Physicians and Surgeons (M.D., 1908). He swiftly ascended the academic ranks, culminating in his appointment as Professor of Surgery at Columbia and Director of Surgical Services at Presbyterian Hospital in 1921. Whipple published three criteria (Whipple's triad) for evaluating hyperinsulinism secondary to pancreatic insulinoma. He also revived interest in portocaval anastomosis to reduce portal hypertension, determining it to be a consequence of liver disease. During his 40-year career, Whipple introduced the concept of multidisciplinary teams and prospective data collection. He also shaped the structure of surgical training as President of the American Surgical Association and Chairman of the American Board of Surgery. Beyond the walls of the operating room, Whipple was a Renaissance Man whose childhood in Persia (Iran) engendered a lifelong interest in the region's art, culture, history, and medicine. Dr. Allen Oldfather Whipple is remembered as a pioneering physician and surgeon beloved by those who trained under him.

Sleep fragmentation engages stress-responsive circuitry, enhances inflammation and compromises hippocampal function following traumatic brain injury.

Traumatic brain injury (TBI) impairs the ability to restore homeostasis in response to stress, indicating hypothalamic-pituitary-adrenal (HPA)-axis dysfunction. Many stressors result in sleep disturbances, thus mechanical sleep fragmentation (SF) provides a physiologically relevant approach to study the effects of stress after injury. We hypothesize SF stress engages the dysregulated HPA-axis after TBI to exacerbate post-injury neuroinflammation and compromise recovery. To test this, male and female mice were given moderate lateral fluid percussion TBI or sham-injury and left undisturbed or exposed to daily, transient SF for 7- or 30-days post-injury (DPI). Post-TBI SF increases cortical expression of interferon- and stress-associated genes characterized by inhibition of the upstream regulator NR3C1 that encodes glucocorticoid receptor (GR). Moreover, post-TBI SF increases neuronal activity in the hippocampus, a key intersection of the stress-immune axes. By 30 DPI, TBI SF enhances cortical microgliosis and increases expression of pro-inflammatory glial signaling genes characterized by persistent inhibition of the NR3C1 upstream regulator. Within the hippocampus, post-TBI SF exaggerates microgliosis and decreases CA1 neuronal activity. Downstream of the hippocampus, post-injury SF suppresses neuronal activity in the hypothalamic paraventricular nucleus indicating decreased HPA-axis reactivity. Direct application of GR agonist, dexamethasone, to the CA1 at 30 DPI increases GR activity in TBI animals, but not sham animals, indicating differential GR-mediated hippocampal action. Electrophysiological assessment revealed TBI and SF induces deficits in Schaffer collateral long-term potentiation associated with impaired acquisition of trace fear conditioning, reflecting dorsal hippocampal-dependent cognitive deficits. Together these data demonstrate that post-injury SF engages the dysfunctional post-injury HPA-axis, enhances inflammation, and compromises hippocampal function. Therefore, external stressors that disrupt sleep have an integral role in mediating outcome after brain injury.

New or Worsened Mitral Regurgitation After Surgical Aortic Valve Replacement: A Systematic Review.

BACKGROUND: New or worsened mitral regurgitation (MR) is an uncommon yet serious complication after surgical aortic valve replacement (SAVR). While there have been numerous reports of its occurrence, there is little consensus regarding its presentation and management. This systematic review summarizes the evidence in the current literature surrounding new or worsened MR after SAVR and analyzes its potential implications. METHODS: Databases were examined for all articles and abstracts reporting on new or worsened MR after SAVR. Data collected included number of patients studied; patient characteristics; incidences of new or worsened MR; timing of diagnosis; and treatment. RESULTS: Thirty-six full-text citations were included in this review. The prevalence of new or worsened MR after SAVR was 8.4%. Sixteen percent of new MR occurrences were from an organic etiology, and 83% of new MR occurrences were that of a functional etiology. Most diagnoses were made in the late or unspecified postoperative period using echocardiography (range: 0 minutes to 18 years postoperatively). While no patients died from this complication, 7.7% of patients (16 out of 207) required emergent procedural re-intervention. CONCLUSIONS: This systematic review underscores the importance of identifying new or worsened MR following SAVR and accurate scoring of MR severity to guide treatment. It also outlines the associated clinical measures commonly documented following this complication, and the usefulness of transesophageal echocardiography for the detection of significant MR. These results reflect the current, limited state of the literature on this topic and warrant further investigation into MR detection and management strategies in SAVR patients.

Comparison between midline and lateral fluid percussion injury in mice reveals prolonged but divergent cortical neuroinflammation.

Animal models are critical for determining the mechanisms mediating traumatic brain injury-induced (TBI) neuropathology. Fluid percussion injury (FPI) is a widely used model of brain injury typically applied either midline or parasagittally (lateral). Midline FPI induces a diffuse TBI, while lateral FPI induces both focal cortical injury (ipsilateral hemisphere) and diffuse injury (contralateral hemisphere). Nonetheless, discrete differences in neuroinflammation and neuropathology between these two versions of FPI remain unclear. The purpose of this study was to compare acute (4-72 h) and subacute (7 days) neuroinflammatory responses between midline and lateral FPI. Midline FPI resulted in longer righting reflex times than lateral FPI. At acute time points, the inflammatory responses to the two different injuries were similar. For instance, there was evidence of monocytes and cytokine mRNA expression in the brain with both injuries acutely. Midline FPI had the highest proportion of brain monocytes and highest IL-1ß/TNFα mRNA expression 24 h later. NanoString nCounter analysis 7 days post-injury revealed robust and prolonged expression of inflammatory-related genes in the cortex after midline FPI compared to lateral FPI; however, Iba-1 cortical immunoreactivity was increased with lateral FPI. Thus, midline and lateral FPI caused similar cortical neuroinflammatory responses acutely and mRNA expression of inflammatory genes was detectable in the brain 7 days later. The primary divergence was that inflammatory gene expression was greater and more diverse subacutely after midline FPI. These results provide novel insight to variations between midline and lateral FPI, which may recapitulate unique temporal pathogenesis.

Sleep Disruption Exacerbates and Prolongs the Inflammatory Response to Traumatic Brain Injury.

Traumatic brain injury (TBI) alters stress responses, which may influence neuroinflammation and behavioral outcome. Sleep disruption (SD) is an understudied post-injury environmental stressor that directly engages stress-immune pathways. Thus, we predicted that maladaptive changes in the hypothalamic-pituitary-adrenal (HPA) axis after TBI compromise the neuroendocrine response to SD and exacerbate neuroinflammation. To test this, we induced lateral fluid percussion TBI or sham injury in female and male C57BL/6 mice aged 8-10 weeks that were then left undisturbed or exposed to 3 days of transient SD. At 3 days post-injury (DPI) plasma corticosterone (CORT) was reduced in TBI compared with sham mice, indicating altered HPA-mediated stress response to SD. This response was associated with approach-avoid conflict behavior and exaggerated cortical neuroinflammation. Post-injury SD specifically enhanced neutrophil trafficking to the injured brain in conjunction with dysregulated aquaporin-4 (AQP4) polarization. Delayed and persistent effects of post-injury SD were determined 4 days after SD concluded at 7 DPI. SD prolonged anxiety-like behavior regardless of injury and was associated with increased cortical Iba1 labeling in both sham and TBI mice. Strikingly, TBI SD mice displayed an increased number of CD45+ cells near the site of injury, enhanced cortical glial fibrillary acidic protein (GFAP) immunolabeling, and persistent expression of Trem2 and Tlr4 7 DPI compared with TBI mice. These results support the hypothesis that post-injury SD alters stress-immune pathways and inflammatory outcomes after TBI. These data provide new insight to the dynamic interplay between TBI, stress, and inflammation.