Brief Report: Risk of Recurrent Interstitial Lung Disease From Osimertinib Versus Erlotinib Rechallenge After Symptomatic Osimertinib-Induced Interstitial Lung Disease.

Introduction: Interstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear. Methods: Retrospective study of 913 patients who received osimertinib treatment for EGFR mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge. Results: Of 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7-12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6-15.0). Conclusions: The risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Risks and impacts of thromboembolism in patients with pancreatic cancer.

INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.

Best practices in epidermal growth factor receptor T790M testing for advanced non-small-cell lung cancer in Hong Kong.

The T790M mutation in the epidermal growth factor receptor gene causes most acquired resistance to firstor second-line epidermal growth factor receptor-tyrosine kinase inhibitors in advanced non-small-cell lung cancer. The results of T790M testing can guide subsequent treatment. Despite the availability of guidelines from international organisations, T790M testing practices in Hong Kong must be streamlined and adapted to the Hospital Authority setting. To address this issue, a panel of experts in oncology and pathology met for discussion of key topics regarding T790M testing practices in Hong Kong, including the appropriate timing of testing and re-testing, as well as optimal testing methods. All panel members voted on the results of the discussion to achieve consensus. Items supported by a majority vote were adopted as consensus statements regarding current best practices for T790M testing in Hong Kong. Among the topics discussed, the panel agreed that T790M testing should be initiated upon radiological progression, including symptomatic disease progression or central nervous system-only progression. The experts also preferred initial testing with liquid biopsy, using the widely available digital polymerase chain reaction platform. This document provides the final consensus statements, as well as a testing and treatment workflow, for clinicians in Hong Kong to use as guidance in T790M testing.

Six-month Follow-up of Cognitive Impairment and Depressive Symptoms in Late-onset Depression.

OBJECTIVE: To assess cognitive performance in elderly depressed patients following treatment for 6 months. Remission rate of depression after 6 months of treatment was calculated. METHODS: The study was performed in a consecutive group of patients aged ≥ 65 years with late-onset depression. Severity of depression was assessed by the Hamilton Depression Scale, cognitive performance by the Hong Kong Montreal Cognitive Assessment, and functional level by the Instrumental Activities of Daily Living Scale. RESULTS: A total of 52 patients were recruited. In all, 28 (53.8%) were found to have cognitive impairment at baseline and 8 (28.6%) of them had improvement after 6 months. This cognitively impaired group was older and had a lower Instrumental Activities of Daily Living Scale score. The remission rate of depression was 61.5%. CONCLUSIONS: Cognitive impairment constituted a stable feature in a considerable number of elderly patients with depression. About two-thirds of patients achieved remission of depression after 6 months of treatment.

Patients committing suicide whilst under the care of the elderly suicide prevention programme of a regional hospital in Hong Kong.

OBJECTIVE: To examine the risk factors for suicide in elderly Hong Kong Chinese. METHODS: Case notes, mortality reports and hospital records of all the patients, who committed suicide from 1 July 2002 to 31 March 2010 whilst under the active care of the Elderly Suicide Prevention Programme of the Castle Peak Hospital in Hong Kong, were reviewed. RESULTS: A total of 1230 elderly with high risk of suicide were assessed and treated from 1 July 2002 to March 2010. A total of 8 patients in this programme who committed suicide during this period were identified, of whom 63% were male and the most frequent method employed was jumping from a height. All the suicides ensued within the first 6 weeks of treatment under the programme. All these patients were diagnosed to have a depressive illness, and all but 1 had an associated physical illness that possibly precipitated the suicide. They had all been admitted to either a mental or general hospital, about 1 month before committing suicide. CONCLUSIONS: The first 2 months of treatment is associated with the highest risk of suicide. Intensive care and support with proper education about effects of antidepressants, and the building-up of a trusted therapeutic alliance with close relatives are particularly important in this vulnerable period.

Electroacupuncture versus celecoxib for neuropathic pain in rat SNL model.

Though acupuncture has long been used to treat various kinds of pain, its mechanisms remain partly understood. Our recent study has shown that it may inhibit cyclooxygenase-2 (COX-2) in the spinal dorsal horn where COX-2 is upregulated after the development of neuropathic pain following spinal nerve ligation (SNL). The current study directly compared the effect of acupuncture with COX-2 inhibitor celecoxib in the spinal cord after SNL in rats. After L5 SNL, the rats were treated either with acupuncture applied to Zusanli (ST36) and Sanyinjiao (SP6) bilaterally with or without electrical stimulation (2 Hz, 0.5-1-2 mA) four times over 22 days, and/or celecoxib fed daily. Paw-withdrawal-threshold to mechanical stimulation and paw-withdrawal-latency to thermal test were tested for neuropathic pain at four intervals following the treatments in comparison with the pre-treatment and non-treatment controls. The results demonstrate that electroacupuncture (EA) had a long lasting and better analgesic effect than celecoxib in reducing neuropathic hypersensitivity. Though COX-2 expression in the spinal L4-L6 dorsal horn by immunostaining was significantly reduced by acupuncture just as well as by celecoxib, the superior analgesic mechanism of acupuncture appears well beyond COX-2 inhibition alone.

Elfin is expressed during early heart development.

Elfin (previously named CLIM1) is a protein that possesses an N-terminal PDZ domain and a C-terminal LIM domain. It belongs to the family of Enigma proteins. Enigma proteins are a family of cytoplasmic proteins that contain an N-terminal PDZ domain and a series of C-terminal LIM domains. By virtue of these two protein interacting domains, Enigma proteins are capable of protein-protein interactions. It has been proposed that Enigma proteins may act as adapters between kinases and the cytoskeleton. We have previously shown that Elfin is most abundantly expressed in the heart and it colocalizes with alpha-actinin 2 at the Z-disks of the myocardium. In this report, Elfin was shown to localize at the actin stress fibers of myoblasts, as revealed by green fluorescent protein (GFP) tagging. In situ hybridization and immunostaining showed that Elfin expression begins at an early stage in mouse development and is present throughout the developing heart. Taken together, our experimental results suggest that Elfin may play an important role in myofibrillogenesis and heart development.

[Thymoma with pure red cell aplasia and hemophagocytic syndrome--one case report].

Erythropoietic hypoplasia occurring in the absence of abnormalities in the leukopoietic and thrombocytopoietic series is often defined as "pure red cell aplasia" (PRCA). This condition may appear as an acquired defect of either acute or chronic type, and a congenital form as well. The chronic form of acquired PRCA occurred mostly in adults. It has been reported that a demonstrable thymoma occurred in more than 50% of patients with PRCA. Recent studies suggested that it may contribute to several immune mechanisms. Here we report a case of thymoma with PRCA whose clinical presentations include severe anemia, shock with severe metabolic acidosis, high levels of several organ enzymes (SGOT, SGPT, LDH, CPK, Amylase) and acute renal shutdown with similar manifestations to septic shock. Our explanation to his condition is multi-organ tissue hypoxia caused by severe anemia. Hemophagocytic syndrome was found by the repeated bone marrow smear before death. The clinical course of this patient was so impressive as to be presented here for discussion.