Patterns of neurotoxicity among patients receiving chimeric antigen receptor T-cell therapy: A single-centre cohort study.

BACKGROUND AND PURPOSE: Immune effector cell-associated neurotoxicity syndrome (ICANS) is an important complication of chimeric antigen receptor T-cell (CAR-T) therapy. This study aims to identify the patterns of neurotoxicity among patients with ICANS at a tertiary referral centre in Australia. METHODOLOGY: This single-centre, prospective cohort study included all consecutively recruited patients who underwent CAR-T therapy for eligible haematological malignancies. All patients underwent a comprehensive neurological assessment and cognitive screening before CAR-T infusion, during the development of ICANS, and 1 month after treatment. Baseline demographic characteristics, incidence, and neurological patterns of neurotoxicity management were evaluated. RESULTS: Over a 19-month period, 23% (12) of the 53 eligible patients developed neurotoxicity (10/12 [83%] being grade 1). All patients showed changes in handwriting and tremor as their initial presentation. Changes in cognition were manifested in most of the patients, with a more substantial drop noted in their Montreal Cognitive Assessment compared to immune effector cell-associated encephalopathy scores. All manifestations of neurotoxicity were short-lived and resolved within a 1-month period, with a mean duration of 8.2 days (range = 1-33). CONCLUSIONS: The patterns of CAR-T-related neurotoxicity often include change in handwriting, tremor, and mild confusional state, especially early in their evolution. These may remain undetected by routine neurological surveillance. These features represent accessible clinical markers of incipient ICANS.

Challenges in the surgical management of spine trauma in the morbidly obese patient: a case series.

OBJECT: The treatment of morbidly obese individuals with spine trauma presents unique challenges to spine surgeons and trauma staff. This study aims to increase awareness of current limitations in the surgical management of spine trauma in morbidly obese individuals, and to illustrate practical solutions. METHODS: Six morbidly obese patients were treated surgically for spine trauma over a 2-year period at a single trauma center in Australia. All patients were involved in high-speed motor vehicle accidents and had multisystem injuries. All weighed in excess of 265 pounds (120 kg) with a body mass index ≥ 40 (range 47.8-67.1). Cases were selected according to the considerable challenges they presented in all aspects of their management. RESULTS: Best medical and surgical care may be compromised and outcome adversely affected in morbidly obese patients with spine trauma. The time taken to perform all aspects of care is usually extended, often by many hours. Customized orthotics may be required. Imaging quality is often compromised and patients may not fit into scanners. Surgical challenges include patient positioning, surgical access, confirmation of the anatomical level, and obtaining adequate instrument length. Postoperative nursing care, wound healing, and venous thromboembolism prophylaxis are also significant issues. CONCLUSIONS: Management pathways and hospital guidelines should be developed to optimize the treatment of morbidly obese patients, but innovative solutions may be required for individual cases.

The association between body mass index and pulmonary thromboembolism in an autopsy population.

To evaluate the association between obesity and pulmonary thromboembolism (PTE) in a forensic context, 160 autopsy cases of fatal PTE were compared with age- and gender-matched controls. The mean age of cases was 66 years (range 26-98 years; M/F 74:86). The mean body mass index (BMI) of cases with PTE was 30.88 (range 14.95-79.51), which was significantly higher than in the controls (mean BMI = 25.33; range 12.49-61.84) (p < 0.0001). Comparing the group with PTE with controls showed that five (3.1%) compared to 20 (12.5%) were underweight, 39 (24.4%) compared to 67 (41.88%) were of normal weight, 49 (30.63%) compared to 43 (26.88%) were overweight, 43 (26.88%) compared to 24 (15%) were obese, and 24 (15.0%) compared to six (3.75%) were morbidly obese. In each category of above-normal BMIs, there were significantly greater numbers in the groups with PTE: overweight (p < 0.01), obese (p < 0.001), and morbidly obese (p < 0.0001).

Is there a relationship between bladder outlet obstruction due to benign prostatic hyperplasia and pulmonary thromboembolism?

Benign prostatic hyperplasia with chronic bladder outlet obstruction has been associated with deep venous thrombosis (DVT) and fatal pulmonary thromboembolism (PTE). To evaluate this further, 60 autopsy cases of men with PTE were compared with 60 age-matched controls. The criteria for outlet obstruction were macroscopic prostatic enlargement with bladder trabeculation and benign prostatic hyperplasia on microscopy. Ten of the 60 men (16.7%) with fatal PTE had evidence of bladder outlet obstruction (age 57-78 years; mean 71.4 years). Of the 60 controls, 12 had evidence of bladder outlet obstruction (20%) (age 67-86 years; mean 75.5 years). No significant relationship could be demonstrated between bladder outlet obstruction and fatal PTE cases (p = 0.8). Given reports of this association, however, it is possible that bladder distension with venous compression may act as a risk modifier in certain individuals in association with other significant comorbidities, but this risk appears low.

Lower extremity deep venous thrombosis with fatal pulmonary thromboembolism caused by benign pelvic space-occupying lesions--an overview.

Venous stasis predisposes to thrombosis. One hundred and sixty cases of fatal pulmonary thromboembolism were reviewed to determine how many cases had deep venous thromboses associated with venous blood flow reduction caused by external pressure from benign pelvic masses. Three cases were identified, representing 2% of cases overall (3/160): a 44-year-old woman with a large uterine leiomyoma (1048 g); a 74-year-old man with prostatomegaly and bladder distension (containing 1 L of urine); and a 70-year-old man with prostatomegaly and bladder distension (containing 3 L of urine). Although a rare cause of fatal deep venous thrombosis and pulmonary thromboembolism, space-occupying pelvic lesions can lead to extrinsic pressure on adjacent veins reducing blood flow and causing stasis and thrombosis. Individuals with large pelvic masses may, therefore, be at increased risk of pulmonary thromboembolism from deep venous thrombosis, particularly in the presence of concurrent risk factors such as immobility, thrombophilias, malignancy, and significant cardiopulmonary disease.