Management of Patients with Cerebellar Ataxia During the COVID-19 Pandemic: Current Concerns and Future Implications

The current worldwide severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that causes coronavirus disease 2019 (COVID-19) has brought some medical systems to the brink of collapse. This crisis is also negatively impacting the care of patients with non-COVID-19 conditions, including those with cerebellar ataxia (CA). Older patients with CA and those with immune-mediated ataxias on immunosuppressive medication are potentially at high risk of developing serious complications of the infection, although it is also possible that immunosuppressive agents may provide a defense against cytokine storm. This has implications for even greater attention to preventing contracting the disease through physical distancing and/or isolation. The CA patient population is also at higher risk because of the neurological complexities of their underlying disorder and the comorbid medical illnesses that often accompany the genetic ataxias. As the disruption of social patterns and healthcare delivery in response to the crisis continues, interruption of rehabilitation, speech and language therapy, and face-to-face consultations threatens to have a negative impact on the course and well-being of CA patients. Mental and physical health is also potentially at greater risk because the prevailing uncertainty and anxiety may be superimposed upon cerebellum-specific neuropsychological challenges. We identify and review some of the short- and long-term consequences of this global pandemic for the community of ataxia patients and their families and for the clinical and academic neurologists/ataxiologists caring for these patients. This includes the recognition that telemedicine has emerged as a principle means of caregiver-patient contact and that neurological manifestations of COVID-19 including those specific to cerebellar neurobiology are increasingly recognized and will require close surveillance and monitoring. This COVID-19 Cerebellum Task Force consensus provides some guidance on how we may approach this uncertain time and consider preparing for the new realities we face in CA patient care once this acute crisis has passed.

     

Experiences of People with Cancer from Rural and Remote Areas of Western Australia Using Supported Accommodation in Perth While Undergoing Treatment

The aim of the study was to explore the lived experiences of people diagnosed with cancer from rural and remote areas of Western Australia, who utilise supported accommodation services whilst undergoing treatment in the capital city (Perth). Methods A qualitative phenomenological approach was used in this study. Ten participants were recruited using purposive sampling, who were aged between 35–65 years, were diagnosed with cancer within the previous three months and used accommodation services within the past 12 months. Semi-structured in-depth interviews were conducted with a duration of approximately 45–60 min via Zoom, FaceTime or phone call. Interview data was transcribed, thematically analysed and coded into relevant themes. Results: Three overarching themes were derived from the interviews–“It’s harder to have cancer when you have to relocate for treatment,” “The paradoxical experience of staying at the accommodation,” and “Feeling grateful for the support offered’. Conclusions: People diagnosed with cancer who have to relocate during treatment require emotional, logistical, and social supports. Cancer accommodation services are essential in enabling individuals to continue engaging in meaningful occupations and maintain their quality of life. Our study highlights the need for cancer accommodation services to consider the complex needs of individuals completing treatment for cancer in locations away from their usual homes.     

CA125 as a serum marker for poor prognosis in ovarian malignancies

In cancer of the ovary, a tumor marker is much needed to assist the conventional methods for monitoring the disease course. All published reports of the CA125 serum immunoassay to date have indicated that rising or falling CA125 levels correlated with disease progression or regression in patients with ovarian malignancies. Our experience with CA125 at the University of Alabama at Birmingham shows that rising CA125 levels are highly suggestive of progressive disease. However, the significance of our findings with CA125 is that, contrary to other reports, falling CA125 levels are not a reliable indicator for regressive disease. Thus, falling CA125 levels are not clinically useful whereas rising CA125 levels may be interpreted as indicative of poor tumor response to therapy, and of the presence of persistent or recurrent disease either prior to second-look laparotomy or during post-treatment follow-up.     

Defective release of vascular plasminogen activator in patients with gynecologic malignancies

Vascular plasminogen activator release was measured in 176 women with gynecologic malignancies and 92 normal women. Releasable plasminogen activator was considerably decreased in the patients (P less than 0.00001 by Wilcoxon's rank sum test) with 59.1% releasing less than 0.04 Committee on Thrombolytic Agents units per milliliter of plasma after a standard venous occlusion procedure. The data were also stratified by tumor location, demonstrating that this decrease in releasable vascular plasminogen activator was seen for ovarian (P = 0.0001), endometrial (P = 0.0017), and cervical (P = 0.0063) cancers. Postoperative deep vein thrombosis, with or without pulmonary emboli, occurred in 28 patients (15.9% incidence). These patients also demonstrated markedly lower levels of releasable vascular plasminogen activator compared to control subjects (P less than 0.0001). It is suggested that defective release of vascular plasminogen activator contributes to a hypercoagulable state in patients with gynecologic malignancies and predisposes to postoperative thromboembolic complications.     

The adverse effects of cervical cancer treatment on bladder function

Bladder dysfunction is a recognized complication following radical hysterectomy, however, the effect of radiation alone or in combination with surgery on bladder function has received little attention. Thirty patients who underwent radical hysterectomy with postoperative whole pelvis radiation (RH + RT) were matched for age, stage of disease, and time interval since therapy, with 30 patients who had radical hysterectomy alone (RH) and 30 patients who were treated with pelvic radiotherapy (RT). Bladder function was assessed by symptoms and urodynamic evaluation. Altered bladder sensation and voiding problems were associated with surgery, and were more frequent after RH or RH + RT than RT (P = 0.002). fifty percent of RH patients voided by abdominal straining compared to 10% who had only RT. No greater problem was seen after RH + RT compared to RH. Urinary incontinence was present in 15% of patients prior to therapy. After treatment, incontinence requiring protection developed in 23% of RT patients, 26% of RH patients, and 63% of RH + RT patients. The severity of the incontinence was greater after RH + RT. Bladder neck and urethral function was similar in all groups, however, bladder compliance was reduced in RT patients and significantly (P = 0.0001) reduced after RH + RT compared to RH alone. This reduction was related to the bladder dose of external radiation and was a factor in the etiology of the urinary incontinence seen in RH + RT patients.     

Intramucosal acidosis and the inflammatory response in acute pancreatitis

OBJECTIVE: The aim of this study was to assess the host response and diminished bowel perfusion during acute pancreatitis. METHODS: A total of 19 patients admitted with established diagnoses of acute pancreatitis on the basis of clinical findings, elevated serum amylase to more than four times the upper limit or by contrast radiology. Patients were stratified into mild and severe pancreatitis using the Atlanta criteria. Blood samples were obtained from in-dwelling lines or direct venipuncture within 12 h of admission and 24 hourly thereafter for measurements of plasma endotoxin, EndoCab immunoglobulin (Ig)G and IgM antibodies, tumor necrosis factor (TNF), p55 TNF receptor, and IL-6. A gastric tonometer was inserted in place of a nasogastric tube for intramucosal pH evaluation. RESULTS: Episodes of endotoxaemia were more common and endotoxin concentration significantly higher at presentation in the severe group compared to the mild group of patients. A greater consumption of IgM antibody was found in those with severe disease. The decrease in IgM antibody concentration was shown to be a specific host response, as a fall in concentration of antibodies to a neutral antigen, tetanus toxoid, was not observed. Significantly greater elevations were found in p55 TNF receptor and IL-6 concentrations in the severe group in comparison to those suffering mild pancreatitis. Significant correlations were found between gastric intramucosal pH and EndoCab IgM antibody, p55 TNF receptor, and IL-6. CONCLUSIONS: These results suggest that endotoxemia, an acute inflammatory response, and a reduction in bowel perfusion may occur in severe acute pancreatitis. The endotoxemia and inflammatory response may be due to the permeation of bacteria and their breakdown products across a disrupted bowel mucosal barrier.     

Detection of p53 gene mutation by rapid PCR-SSCP and its association with poor survival in breast cancer

We examined the association between mutation of the p53 gene and survival in a large cohort of breast cancer patients. Using a rapid, non-isotopic single-strand conformation polymorphism (SSCP) method we screened for mutations in exons 4–10 of the p53 gene in 375 primary breast cancers from patients with a median follow-up of 57 months. Mutations were found in 19% of tumours. Statistically significant associations were found between p53 mutation and histological grade, hormone receptor status, ploidy and S-phase fraction. No association was found between p53 mutation and axillary lymph node involvement, histological type, tumour size, vascular invasion or patient age. In univariate survival analysis, p53 mutation was strongly associated with poor prognosis. This was maintained in the lymph node-negative and hormone receptor-positive patient subgroups. In multivariate analysis, p53 mutation was associated with poor survival independent of lymph node status, estrogen receptor status and S-phase fraction. Our results demonstrate the feasibility of using a rapid and simple polymerase chain reaction-SSCP screening procedure to detect p53 gene mutation in breast cancer for the provision of prognostic information. Int. J. Cancer 74:642–647, 1997.© 1997 Wiley-Liss, Inc.     

Mutation of the transforming growth factor-β type II receptor gene in right-sided colorectal cancer: relationship to clinicopathological features and genetic alterations

The presence of inactivating mutations in the transforming growth factor-β (TGF-β) type II receptor (RII) gene in colon cancer suggests that it may behave like a tumour suppressor gene. RII is mutated in the majority of colon tumours exhibiting widespread microsatellite instability, a characteristic generally referred to as the replication error phenotype (RER+). We investigated the association between RII mutations and various clinicopathological variables and genetic alterations in a large series of sporadic adenocarcinomas arising in the proximal colon. RII mutations were found in 17 per cent (36/210) of right-sided tumours and in 86 per cent (32/37) of those displaying RER+. They were associated with the absence of lymph node invasion (P=0·04), poor histological differentiation (P=0·006), and with a trend for improved patient survival. Tumours with an RII mutation also showed non-significant trends for a lower incidence of p53 protein overexpression and of p53, K-ras, and APC gene mutation compared with tumours with normal RII. These results indicate that right-sided colorectal tumours containing RII mutations resemble those with the RER+ phenotype in terms of their clinicopathological features and genetic alterations. © 1998 John Wiley & Sons, Ltd.