Risk factors for postoperative complications after adrenalectomy for phaeochromocytoma: multicentre cohort study.

BACKGROUND: To determine the incidence and risk factors for postoperative complications and prolonged hospital stay after adrenalectomy for phaeochromocytoma. METHODS: Demographics, perioperative outcomes and complications were evaluated for consecutive patients who underwent adrenalectomy for phaeochromocytoma from 2012 to 2020 in nine high-volume UK centres. Odds ratios were calculated using multivariable models. The primary outcome was postoperative complications according to the Clavien---Dindo classification and secondary outcome was duration of hospital stay. RESULTS: Data were available for 406 patients (female n = 221, 54.4 per cent). Two patients (0.5 per cent) had perioperative death, whilst 148 complications were recorded in 109 (26.8 per cent) patients. On adjusted analysis, the age-adjusted Charlson Co-morbidity Index ≥3 (OR 8.09, 95 per cent c.i. 2.31 to 29.63, P = 0.001), laparoscopic converted to open (OR 10.34, 95 per cent c.i. 3.24 to 36.23, P <0.001), and open surgery (OR 11.69, 95 per cent c.i. 4.52 to 32.55, P <0.001) were independently associated with postoperative complications. Overall, 97 of 430 (22.5 per cent) had a duration of stay ≥5 days and this was associated with an age-adjusted Charlson Co-morbidity Index ≥3 (OR 4.31, 95 per cent c.i. 1.08 to 18.26, P = 0.042), tumour size (OR 1.15, 95 per cent c.i. 1.05 to 1.28, P = 0.006), laparoscopic converted to open (OR 32.11, 95 per cent c.i. 9.2 to 137.77, P <0.001), and open surgery (OR 28.01, 95 per cent c.i. 10.52 to 83.97, P <0.001). CONCLUSION: Adrenalectomy for phaeochromocytoma is associated with a very low mortality rate, whilst postoperative complications are common. Several risk factors, including co-morbidities and operative approach, are independently associated with postoperative complications and/or prolonged hospitalization, and should be considered when counselling patients.

Risk factors for postoperative hypotension after adrenalectomy for phaeochromocytoma: derivation of the PACS risk score.

BACKGROUND: Due to the risk of postoperative hypotension (PH), invasive monitoring is recommended for patients who undergo adrenalectomy for phaeochromocytoma. Due to high costs and limited availability of intensive care, our aim was to identify patients at low risk of PH who may not require invasive monitoring. METHODS: Data for patients who underwent adrenalectomy for phaeochromocytoma between 2012 and 2020 were retrospectively collected by nine UK centres, including patient demographics, intraoperative and postoperative haemodynamic parameters. Independent risk factors for PH were analysed and used to develop a clinical risk score. RESULTS: PH developed in 118 of 430 (27.4%) patients. On univariable analysis, female sex (p = 0.007), tumour size (p < 0.001), preoperative catecholamine level (p < 0.001), open surgery (p < 0.001) and epidural analgesia (p = 0.006) were identified as risk factors for PH. On multivariable analysis, female sex (OR 1.85, CI95%, 1.09-3.13, p = 0.02), preoperative catecholamine level (OR: 3.11, CI95%, 1.74-5.55, p < 0.001), open surgery (OR: 3.31, CI95%, 1.57-6.97, p = 0.002) and preoperative mean arterial blood pressure (OR: 0.59, CI95%, 0.48-1.02, p = 0.08) were independently associated with PH, and were incorporated into a clinical risk score (AUROC 0.69, C-statistic 0.69). The risk of PH was 25% and 68% in low and high risk patients, respectively. CONCLUSION: The derived risk score allows stratification of patients at risk of postoperative hypotension after adrenalectomy for phaeochromocytoma. Postoperatively, low risk patients may be managed on a surgical ward, whilst high risk patients should undergo invasive monitoring.

Quantitative Assessment of Response to Long-Term Treatment with Intravenous Immunoglobulin in Patients with Stiff Person Syndrome.

BACKGROUND: Stiff person syndrome (SPS) is an autoimmune condition involving antibodies against several components of the inhibitory synapse in the spinal cord, with glutamic acid decarboxylase antibodies being the predominant immune marker. SPS affects approximately 1 patient per million population per year. The effect of intravenous immunoglobulin (IVIG) has been established, but studies on the long-term efficacy of regular IVIG are limited. OBJECTIVES: To review clinical details and long-term treatment response using a patient-reported questionnaire in SPS and related syndromes. METHODS: Patients were identified from a tertiary neuroimmunology clinic based on classical clinical symptoms, autoimmune profiles, and neurophysiological changes (Dalakas criteria). They were followed up after treatment to assess the response to IVIG. RESULTS: A total of 23 patients fulfilled the selection criteria. Patients' demographic profiles and clinical presentations were akin to that reported in literature. There was significant improvement in the functional ability (assessed by the modified Rankin scale [mRS]) and quality of life (QoL) following treatment with IVIG within 4 to 10 weeks (pre-mRS vs. post-mRS, P < 0.0001; pre-QoL vs. post-QoL, P = 0.0003) and sustained after 5 years of treatment (pre-mRS vs. present mRS, P = 0.0003; pre-QoL vs. present QoL, P = 0.0002). CONCLUSIONS: This article describes one of the largest single-center experiences of 23 patients with SPS and related syndromes and is the first to establish the long-term efficacy of regular IVIG using a patient-reported scoring system (Birmingham Response to Immunomodulatory Therapy [BRIT]). Consistent improvement in QoL and functional scores were seen over nearly 5 years after regular use of IVIG. It is recommended to use BRIT scores to assess the initial response as well as to monitor continued improvement to immunomodulation in SPS.

Incidence, risk factors and clinical significance of postoperative haemodynamic instability after adrenalectomy for phaeochromocytoma.

BACKGROUND: Due to risk of haemodynamic instability (HDI), it has been recommended that patients undergoing adrenalectomy for phaeochromocytoma should be monitored in an intensive care facility. The aim of this study was to evaluate the incidence, risk factors and outcomes of postoperative HDI in these patients. Retrospective cohort study of 46 consecutive patients who underwent open (OA, N=26) or laparoscopic (LA, N=20) adrenalectomy for phaeochromocytoma at a single centre [2007-2017]. METHODS: HDI was defined as systolic BP >200 or <90 mmHg, heart rate >120 or <50 bpm or vasopressor therapy within 24 hours. Risk factors for intraoperative and postoperative HDI were evaluated by univariable and multivariable analyses. RESULTS: Intraoperative hypertension occurred in 25/42 patients (60%). Preoperative plasma normetanephrine levels ≥3,500 pmol/L were significantly associated with intraoperative hypertension on multivariable analysis [odds ratio (OR) 42; 95% CI: 4-429; P=0.002). Postoperative hypotension occurred in 21/45 patients (47%), and 13 (29%) required vasopressor therapy. Preoperative beta-blockade therapy was the only independent risk factor for postoperative hypotension on multivariable analysis (OR 4.0; 95% CI: 1.2-13.9, P=0.029). No patients (0/9) with tumours <5 cm treated by LA needed postoperative vasopressor therapy, compared to 39% (7/18) treated by OA (P=0.059). Complications developed in 9 patients (20%), and were less likely in those with intraoperative hypertension (8% vs. 41%; P=0.019). There was one postoperative death. CONCLUSIONS: Preoperative beta-blockade therapy is an independent risk factor for postoperative HDI after adrenalectomy for phaeochromocytoma. Patients who undergo laparoscopic adrenalectomy (LA) for phaeochromocytomas <5 cm are unlikely to need postoperative vasopressor therapy, and may not require intensive care monitoring.

A missense variant in CST3 exerts a recessive effect on susceptibility to age-related macular degeneration resembling its association with Alzheimer's disease.

Age-related macular degeneration (AMD) and Alzheimer's disease (AD) are degenerative, multifactorial diseases involving age-related accumulation of extracellular deposits linked to dysregulation of protein homeostasis. Here, we strengthen the evidence that an nsSNP (p.Ala25Thr) in the cysteine proteinase inhibitor cystatin C gene CST3, previously confirmed by meta-analysis to be associated with AD, is associated with exudative AMD. To our knowledge, this is the first report highlighting a genetic variant that increases the risk of developing both AD and AMD. Furthermore, we demonstrate that the risk associated with the mutant allele follows a recessive model for both diseases. We perform an AMD-CST3 case-control study genotyping 350 exudative AMD Caucasian individuals. Bringing together our data with the previously reported AMD-CST3 association study, the evidence of a recessive effect on AMD risk is strengthened (OR = 1.89, P = 0.005). This effect closely resembles the AD-CST3 recessive effect (OR = 1.73, P = 0.005) previously established by meta-analysis. This resemblance is substantiated by the high correlation between CST3 genotype and effect size across the two diseases (R(2) = 0.978). A recessive effect is in line with the known function of cystatin C, a potent enzyme inhibitor. Its potency means that, in heterozygous individuals, a single functional allele is sufficient to maintain its inhibitory function; only homozygous individuals will lack this form of proteolytic regulation. Our findings support the hypothesis that recessively acting variants account for some of the missing heritability of multifactorial diseases. Replacement therapy represents a translational opportunity for individuals homozygous for the mutant allele.