Distinguishing features of COVID-19 and non-COVID-19 febrile seizures in hospitalised children.

INTRODUCTION: Febrile seizures in children can be associated with various underlying conditions, including COVID-19. Differentiating COVID-19 and non-COVID-19 related febrile seizures is crucial for tailored patient management and for implementing appropriate infection control measures to prevent nosocomial transmission. This study aimed to describe the clinical features of children hospitalised for COVID-19 and non-COVID-19 febrile seizures and to identify factors that differentiate between the two groups. MATERIALS AND METHODS: This retrospective cross-sectional study involved children aged 6 months to 6 years who were hospitalised for febrile seizures in Hospital Tuanku Ja'afar Seremban (HTJS) from January 2021 to June 2022. Descriptive statistics were used to summarise the differences in demographics and clinical presentations. Logistic regression analyses were performed to identify factors associated with COVID-19 and non-COVID-19 febrile seizures. RESULTS: Of the 345 patients (median age 22 months, IQR 15- 32; 59.7% were males) included in the study, 130 (37.7%) tested positive for COVID-19, while 215 (62.3%) tested negative. There were no significant differences between both groups based on age, comorbidities, history of febrile seizures, seizure types, temperature on arrival, cough and rhinorrhoea. Multivariate analysis revealed that a family history of febrile seizures and leucocytosis were associated with increased odds of non-COVID-19 febrile seizures. In contrast, lymphopenia was associated with decreased odds. CONCLUSION: The clinical presentation of COVID-19 and non- COVID-19 febrile seizures are remarkably similar, highlighting the importance of including COVID-19 screening in febrile seizures workup. Full blood count readings may be potentially useful for differentiating between these conditions.

Prognostic implication of the neoadjuvant rectal score and other biomarkers of clinical outcome in Hong Kong Chinese patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy is a standard treatment for locally advanced rectal cancer, for which pathological complete response is typically used as a surrogate survival endpoint. Neoadjuvant rectal score is a new biomarker that has been shown to correlate with survival. The main objectives of this study were to investigate factors contributing to pathological complete response, to validate the prognostic significance of neoadjuvant rectal score, and to investigate factors associated with a lower neoadjuvant rectal score in a cohort of Hong Kong Chinese. METHODS: Data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy from August 2006 to October 2018 were retrieved from hospital records and retrospectively analysed. RESULTS: Of 193 patients who had optimal response to neoadjuvant chemoradiotherapy and surgery, tumour down-staging was the only independent prognostic factor that predicted pathological complete response (P<0.0001). Neoadjuvant rectal score was associated with overall survival (hazard ratio [HR]=1.042, 95% confidence interval [CI]=1.021-1.064; P<0.0001), disease-free survival (HR=1.042, 95% CI=1.022-1.062; P<0.0001), locoregional recurrence-free survival (HR=1.070, 95% CI=1.039-1.102; P<0.0001) and distant recurrence-free survival (HR=1.034, 95% CI=1.012-1.056; P=0.002). Patients who had pathological complete response were associated with a lower neoadjuvant rectal score (P<0.0001), but pathological complete response was not associated with survival. For patients with intermediate neoadjuvant rectal scores, late recurrences beyond 72 months from diagnosis were observed. CONCLUSION: Neoadjuvant rectal score is an independent prognostic marker of survival and disease recurrence in a cohort of Hong Kong Chinese patients who received neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Adverse events following BNT162b2 mRNA COVID-19 vaccination among healthcare workers: A single-centre experience in Malaysia.

INTRODUCTION: The COVID-19 pandemic is a global health crisis that has resulted in a massive disease burden worldwide. Mass vaccination plays an important role in controlling the spread and severity of COVID-19 infections worldwide. MATERIALS AND METHODS: A cross-sectional study was conducted in Hospital Tuanku Ja'afar Seremban between 1 March 2021 and 4 May 2021 to describe the adverse events (AE) following BNT162b2 (Pfizer-BioNTech) vaccination. Healthcare personnel who received at least one dose of the vaccine were invited to complete an online questionnaire. RESULTS: Of 2282 analysed samples, AE were experienced in up to 64.5% (n=1472) of the study participants. Most AE were encountered after the second dose (56.5%, n=832). Pain at the injection site (41.5%, n=944), fever (35.1%, n=798) and lethargy (34.8%, n=792) were the most commonly reported AE. Severe AEFI were reported in a minority (2.9%, n=68). There were no documented anaphylaxis, vaccine-induced thrombosis, or myocarditis. The proportion of female recipients and recipients with a history of allergy were higher in the AE group compared to the non-AE group. CONCLUSION: Our study reinforces the safety of the BNT162b2 mRNA vaccine in the local population. The main adverse events were mild, although they occurred in most patients.

The outcome of laparoscopic colorectal resection in T4 cancer.

AIM: Laparoscopic surgery for locally advanced tumours with extramural involvement is still controversial. It is believed that laparoscopic excision of T4 cancers is technically difficult and may result in prolonged operative time, increased conversion rate, added postoperative morbidity, and suboptimal oncological clearance. METHOD: Our unit has been practising laparoscopic colorectal surgery since 1992, and all data are entered into a database prospectively. Since 1999 we have routinely used the laparoscopic approach for colorectal cancer resections. Data regarding patients with a histologically T4 cancer operated on between 1999 and 2008 were analysed. Outcomes included operating time, conversion rate, postoperative complications and oncological outcome. RESULTS: Over a 10-year period, 146 patients (male 75) with a T4 cancer underwent laparoscopic resection. The median operating time was 125 (range, 46-285) min and the median blood loss was 50 (0-1800) ml. The conversion rate was 16%. Six (4.1%) patients experienced anastomotic leakage. The median number of lymph nodes harvested was 13 (2-40). One hundred and two (70%) patients underwent curative resection. The recurrence rates were 41% and 53% for stage II and III patients, respectively. Four (3.9%) patients had local recurrence. At a median follow up of 18 (1-118) months, the overall survival was 25 months, with median overall survival for patients with stage II, III and IV disease being 63, 36 and 12 months, respectively. CONCLUSION: Laparoscopic colectomy in histologically T4 cancer is safe. Oncological outcomes remain satisfactory. Based on our data, provided expertise is available, patients with locally advanced tumours should not be excluded from a laparoscopic approach.

High SUV uptake on FDG-PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG-PET/CT staging in lymphoma.

BACKGROUND: Data assessing the role of positron emission tomography (PET)/computed tomography (CT) imaging in lymphoma staging is still being accumulated and current staging is based primarily on CT. This study aims to compare the value of PET/CT over conventional CT and bone marrow biopsy (BMB) in the initial evaluation of patients with lymphoma. METHODS: Data on 122 patients with PET/CT scans as part of their initial staging were prospectively collected and reviewed. All patients had complete staging, including BMB. RESULTS: Among the 122 patients, 101 had non-Hodgkin's lymphoma (NHL) and 21 had Hodgkin's lymphoma (HL). Compared with conventional CT, PET/CT upstaged 21 (17%) cases [B-cell non-Hodgkin's lymphoma (B-NHL), 12; T-cell non-Hodgkin's lymphoma (T-NHL), 3; HL, 6]. Of significance, in 13 patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-avid splenic lesions, four had normal CT findings. A maximum FDG uptake of >10 standardized uptake value (SUV) seems to significantly correlate with an aggressive B-cell lineage (odds ratio 2.47, 95% confidence interval 2.23-2.70). Overall, PET scan was concordant with BMB results in 108 (89%) and discordant in 14 (11%) cases. In HL, our data show that PET scan and marrow results agreed in 19 of the cases (90%), being concordantly negative in 18 cases and concordantly positive in one, giving a negative predictive value (NPV) of 100%, sensitivity of 100% and specificity of 90%. Of note, all 13 with early-stage HL had negative PET/CT scan and BMB. In NHL, all 17 cases of T-NHL had concordant PET and BMB results. In patients with aggressive B-NHL, BMB and PET/CT agreed in 58 patients (92%) and disagreed in five (8%), while the corresponding rates in indolent B-cell lymphoma were 14 (67%) and seven patients (33%), respectively. All seven were falsely negative. CONCLUSIONS: PET/CT upstages 17% of cases and detects occult splenic involvement. This may have potential therapeutic and prognostic implications. SUV >10 may predict for an aggressive histology. Except for indolent B-NHL, our data show that PET scans have a good overall NPV in excluding lymphomatous bone marrow involvement. This is particularly true of early-stage HL, suggesting that BMB may be safely omitted in this group.

Obstructive complications of laparoscopically created defunctioning ileostomy.

PURPOSE: The use of defunctioning ileostomy is a common practice to reduce the septic complications after anastomotic leakage in colorectal surgery. In open surgery, the fashioning of ileostomy is a straightforward procedure. However, in the laparoscopic approach, this can be a difficult task and obstructive complications can occur postoperatively. METHODS: A retrospective review was undertaken for all patients who underwent laparoscopic colorectal resection and defunctioning loop ileostomy over a 15-year period. RESULTS: In this period, 161 patients underwent laparoscopic colorectal surgery with defunctioning ileostomy. Eight patients developed obstructive complications in the early postoperative period requiring surgical intervention (5 percent). All patients presented with intestinal obstruction from the fourth to the sixth postoperative day. The median time to reoperation was 9.5 days (range, 5 to 19). The causes of obstructive complications were twisting of the ileostomy (n = 3), adhesive kinking proximal to the ileostomy (n = 3), tight fascia (n = 1), and both tight fascia and twisting of ileostomy (n = 1). Six patients underwent laparotomy for diagnosis and refashioning of ileostomy. The seventh patient had endoscopic decompression of small bowel and refashioning of ileostomy. The last patient was successfully managed with combined endoscopic and laparoscopic approach. CONCLUSIONS: Various pitfalls can occur in laparoscopically created defunctioning ileostomy. Measures can be taken to minimize these technical errors. Various surgical reinterventions can be attempted to determine the cause. With combined uses of enteroscope and laparoscope, a laparotomy can be avoided.

Properties of matter matter in assessment of scald injuries.

Gathering information on the thermal characteristics of the causative agent in scald injuries provides clues as to the likely depth of injury. We theorize that viscosity and thermal capacity may have important roles to play when we view scalds as contact burns due to a liquid. From a 4-year review of our scald patients, we found that scalds due to thick food/drinks such as congee (a porridge made from rice) were associated with a higher rate of surgery. We determined the rate of cooling of seven common food/drinks and found little difference between water, tea, coffee and noodles, other than the starting temperatures. However, the rate of cooling of congee was significantly slower indicating a greater thermal capacity. A "drip" model found that a skin substitute exposed to congee cooled significantly more slowly compared to other food/drinks, suggesting that its greater viscosity plays a role. This supports the theory that the viscosity of food/drink is important.

Stathmin mediates neuroblastoma metastasis in a tubulin-independent manner via RhoA/ROCK signaling and enhanced transendothelial migration.

Neuroblastoma, the most common solid tumor of young children, frequently presents with aggressive metastatic disease and for these children the 5-year survival rates are dismal. Metastasis, the movement of cancer cells from one site to another, involves remodeling of the cytoskeleton including altered microtubule dynamics. The microtubule-destabilizing protein, stathmin, has recently been shown to mediate neuroblastoma metastasis although precise functions remain poorly defined. In this study we investigated stathmin's contribution to the metastatic process and potential mechanism(s) by which it exerts these effects. Stathmin suppression significantly reduced neuroblastoma cell invasion of 3D tumor spheroids into an extracellular matrix. Moreover, inhibiting stathmin expression significantly reduced transendothelial migration in two different neuroblastoma cell lines in vitro. Inhibition of ROCK, a key regulator of cell migration, in neuroblastoma cells highlighted that stathmin regulates transendothelial migration through ROCK signaling. Reduced stathmin expression in neuroblastoma cells significantly increased the activation of the RhoA small GTPase. Notably, re-expression of either wild type or a phospho-mimetic stathmin mutant (4E) made defective in tubulin binding returned cell migration and transendothelial migration back to control levels, indicating that stathmin may influence these processes in neuroblastoma cells independent of tubulin binding. Finally, stathmin suppression in neuroblastoma cells significantly reduced whole body, lung, kidney and liver metastases in an experimental metastases mouse model. In conclusion, stathmin suppression interferes with the metastatic process via RhoA/ROCK signaling in neuroblastoma cells. These findings highlight the importance of stathmin to the metastatic process and its potential as a therapeutic target for the treatment of neuroblastoma.

Colonic amoebic abscess mimicking carcinoma of the colon.

Amoebiasis is an uncommon disease in developed countries. Its clinical presentation can be variable and non-specific, and the diagnosis can be easily overlooked. We report a case of colonic amoebic abscess mimicking advanced colonic cancer with acute intestinal obstruction and liver metastasis. The presentation, diagnosis, and treatment of amoebiasis are also reviewed.

Initial experience in use of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography in thyroid carcinoma patients with elevated serum thyroglobulin but negative iodine-131 whole body scans.

INTRODUCTION: This study aims to examine the usefulness of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in thyroid carcinoma patients with elevated serum thyroglobulin (Tg) but negative iodine-131 (I-131) whole body scans. METHODS: 17 patients with differentiated thyroid carcinoma who underwent FDG PET/CT scans were reviewed retrospectively over a period of one year from July 2003 to June 2004. All these patients had completion thyroidectomy and subsequently presented with elevated serum Tg but negative post-therapy I-131 whole body scans. Nine of these patients underwent FDG PET/CT in a hypothyroid state, while the remainder underwent FDG PET/CT while on thyroxine replacement. RESULTS: 15 out of 17 PET/CT scans revealed lesions consistent with metastases, giving a sensitivity of 88.2 percent. Four of these patients were amendable to surgical treatment. Two scans were negative. CONCLUSION: FDG PET/CT is a sensitive diagnostic tool to detect radioiodine-negative recurrences/metastases in patients with thyroid carcinoma. Our preliminary results are comparable with published results based on PET.

Oxysterols induce differentiation in human keratinocytes and increase Ap-1-dependent involucrin transcription.

Ligands and activators of the nuclear hormone receptor superfamily are important in the regulation of epidermal development and differentiation. Previously, we showed that naturally occurring fatty acids, as well as synthetic ligands for the peroxisome proliferator-activated receptor, induce keratinocyte differentiation in vitro. Here we asked whether oxysterols, another class of lipids formed de novo in the epidermis and that activate liver X-activated receptor, regulate keratinocyte differentiation. mRNA and protein levels of involucrin and transglutaminase 1, markers of differentiation, increased 2- to 3-fold in normal human keratinocytes incubated in the presence of 25- or 22R-hydroxycholesterol in low calcium. In high calcium, which alone induces differentiation, mRNA levels were further increased by oxysterols. Rates of cornified envelope formation, an indicator of terminal differentiation, also increased 2-fold with oxysterol treatment. In contrast, the rate of DNA synthesis was inhibited approximately 50% by oxysterols. Transcriptional regulation was assessed in keratinocytes transfected with either transglutaminase 1 or involucrin promoter-luciferase constructs. 22R-hydroxycholesterol increased transglutaminase 1 and involucrin promoter activity 2- to 3-fold. Either deletion of the -2452 bp to -1880 bp region of the involucrin promoter, or mutation of the AP-1 site within this region, abolished oxysterol responsiveness. Moreover, increased AP-1 DNA binding was observed in oxysterol-treated keratinocytes by gel shift analyses. Finally, we demonstrated the presence of liver X-activated receptor alpha and beta mRNAs, and showed that oxysterols stimulate a liver X-activated receptor response element transfected into keratinocytes. These data suggest that oxysterols induce keratinocyte differentiation, in part through increased AP-1-dependent transcription of the involucrin gene, an effect that may be mediated by liver X-activated receptor.

Stimulation of PPARalpha promotes epidermal keratinocyte differentiation in vivo.

Our recent studies have demonstrated that PPARalpha activators stimulate differentiation and inhibit proliferation in cultured human keratinocytes and accelerate epidermal development and permeability barrier formation in fetal rat skin explants. As the role of PPARalpha activation in adult epidermis is not known, the aim of this study was to determine if topically applied PPARalpha ligands regulate keratinocyte differentiation in murine epidermis. Topical treatment with PPARalpha activators resulted in decreased epidermal thickness. Expression of structural proteins of the upper spinous/granular layers (involucrin, profilaggrin-filaggrin, loricrin) increased following topical treatment with PPARalpha activators. Furthermore, topically applied PPARalpha activators also increased apoptosis, decreased cell proliferation, and accelerated recovery of barrier function following acute barrier abrogation. Experiments with PPARalpha-/- knockout mice showed that these effects are specifically mediated via PPARalpha. Compared with the epidermis of PPARalpha+/+ mice, involucrin, profilaggrin-filaggrin, and loricrin expression were slightly decreased in PPARalpha-/- mice. Moreover, topical clofibrate treatment did not increase epidermal differentiation in PPARalpha-/- mice. Furthermore, in cultured human keratinocytes we have demonstrated that PPARalpha activators induce an increase in involucrin mRNA levels. We have also shown that this increase in gene expression requires an intact AP-1 response element at -2117 to -2111 bp. Thus, stimulation of PPARalpha stimulates keratinocyte/epidermal differentiation and inhibits proliferation.

Regulation of involucrin gene expression by calcium in normal human keratinocytes.

Calcium is essential for normal epidermal differentiation. Data from Northern and nuclear run-on analysis indicate that involucrin gene transcription is induced by 1.2 mM extracellular calcium. A 3.7 Kbp fragment of the involucrin gene, which contains 2.5 Kbp of upstream region, the transcription start site, and the first intron, was sub-cloned into the pGL3-basic luciferase reporter vector and transfected into pre-confluent normal human keratinocytes (NHK). The stimulated activities of this clone were above basal levels and was further enhanced eight-fold by 1.2 mM extracelluar calcium. The results from a series of truncation and internal deletion experiments revealed multiple calcium-independent enhancer elements between -2476 and -2131 bp of the transcription start site and a calcium-dependent element between -2131 and -2028 bp. This 103 bp fragment contains sequences of an AP-1 site (TGAGTCA), a SP-1 site (GGGCGG), and shares homology with two elements in the human keratin-1 promoter, within the regions identified as mediating the calcium responsiveness of that gene in keratinocytes. One or more of these putative elements may be involved in the calcium-dependent regulation of the involucrin gene transcription in NHK.

99mTc-sestamibi and 131I whole-body scintigraphy and initial serum thyroglobulin in the management of differentiated thyroid carcinoma.

UNLABELLED: 99mTc-sestamibi whole-body scanning has been used in the postoperative assessment of differentiated thyroid carcinoma together with 131I whole-body scanning and serum thyroglobulin (Tg) estimation. This study compared 99mTc-sestamibi whole-body scanning with 131I whole-body scanning in the context of initial serum Tg levels of patients after total or near-total thyroidectomy who were taken off thyroxine suppression therapy and who had no 131I ablation before surgery. METHODS: A prospective study of 360 patients was undertaken. 99mTc-sestamibi whole-body scintigraphy was performed at least 5 wk after thyroidectomy and was followed by 131I whole-body scanning. The patients had no thyroxine suppression for 5 wk, and Tg was measured thereafter. Radiologic studies (chest radiography, CT, MRI, sonography, and bone scanning) and histopathologic examinations were performed to clarify the presence of metastases with positive uptake on either 99mTc-sestamibi scans or 131I whole-body scans. Positive scans were defined as those with the presence of thyroid remnants, lymph node disease, or metastases. RESULTS: Two hundred fifty-nine (71.9%) of the 360 patients had initial serum Tg levels < 30 ng/mL (group 1), whereas 101 (28.1%) had initial serum Tg levels > or = 30 ng/mL (group 2). Of the 259 group 1 patients, 82 had positive 99mTc-sestamibi scans and 113 had positive 131I scans; 71.7% of patients with positive 1311 scans also had positive 99mTc-sestamibi scans, and 98.8% of patients with positive 99mTc-sestamibi scans also had positive 131I scans. Of the 101 group 2 patients, 81 had positive 99mTc-sestamibi scans and 97 had positive 131I scans; 83.5% of patients with positive 131I scans also had positive 99mTc-sestamibi scans, and all patients with positive 99mTc-sestamibi scans also had positive 131I scans. Of those with initial serum Tg levels > or = 30 ng/mL (group 2), 27.2% had thyroid remnants and 68.8% had lymph node disease or metastases. 131I scanning detects more thyroid remnants and lung metastases than does 99mTc-sestamibi scanning. CONCLUSION: Our findings suggest that, compared with 131I scanning, 99mTc-sestamibi scanning is less sensitive in detecting thyroid remnants and lung metastases but appears to be more useful in the detection of lymph node disease before initial 131I treatment.

Thyrotoxicosis due to the simultaneous occurrence of silent thyroiditis and Graves' disease.

Silent thyroiditis (ST) and Graves' disease (GD) are two clinical entities belonging to the wide spectrum of autoimmune thyroid diseases (AITD). The two diseases are closely linked because sequential development of GD followed by ST, or the reverse course of events, ie, ST followed by GD, have been documented. However, the pathogenetic basis of the above association remains unknown. Some authors have suggested that the concomitant existence of ST and activation of GD can occur in thyrotoxic postpartum women with normal radioiodoine uptake. The simultaneous occurrence of the two diseases in different parts of the same thyroid gland has, however, to our knowledge, not been documented. We report the case of a 40-year-old thyrotoxic female with atypical presentation of GD. The titers of the antithyrotropin receptor antibodies were elevated and her initial 99mTc-pertechnetate thyroid scan showed the coexistence of ST and GD in different parts of the thyroid gland. Through serial thyroid scans, we document the recovery from ST in parts of the gland and demonstrate the progression to Graves' hyperthyroidism in the entire gland.

Intermediate probability lung scans (IPLS): retrospective review of 82 cases.

OBJECTIVE: In the light of a reported 30-40% prevalence of pulmonary embolism (PE) in intermediate probability lung scans (IPLS) based on results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study, we examined the frequency of documented PE in 82 patients with IPLS, the management strategy employed in these patients with regards to additional imaging (e.g. further evaluation with venous sonography or spiral computed tomographic angiography (CTA)), anticoagulation therapy, and subsequent follow-up outcomes. METHOD: Retrospective review of the medical records of 82 patients with intermediate probability ventilation-perfusion (V/Q) lung scans from January 1998 to July 1999. RESULTS: 14.1% of V/Q scans were reported as having an intermediate probability of PE. 72% of IPLS were subject to further evaluation with venous Doppler ultrasound and/or CTA, and 39% of these patients had evidence of thrombo-embolic disease. All patients with imaging evidence of thromboembolic disease were started on anticoagulation therapy. In addition, 19 patients were treated based on clinical judgement. Amongst the 35 patients who were not treated, 17 (49%) were based on clinical findings without further imaging. There was no mortality on follow-up of 28 cases of untreated IPLS. CONCLUSION: The majority of IPLS will have further imaging, out of which over one-third will have thrombo-embolic disease. Approximately half of IPLS cases will receive anticoagulation therapy. No mortality or PE was found on follow-up of patients who were not treated.

Radionuclide imaging in primary hyperparathyroidism using 99mTc sestamibi--four case reports.

Radionuclide imaging using the 99mTc sestamibi either singly or as a subtraction technique with pertechnetate is a recent and reliable method in localising parathyroid adenomas prior to surgery. This is of use in pre-operative planning, as well as in failed first neck exploration. Four local patients with primary hyperparathyroidism whose parathyroid adenomas were localised by this scintigraphy are presented. The value and limitations of this imaging modality are discussed.

Hereditary haemorrhagic telangiectasia with pulmonary arteriovenous malformations: a treatable cause of thromboembolic cerebral events.

Hereditary haemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is associated with mucocutaneous telangiectases and iron deficiency anaemia caused by epistaxis or blood loss from the gastrointestinal tract. We describe a 41-year-old Chinese man who presented with amaurosis fugax secondary to emboli from pulmonary arteriovenous malformations associated with HHT. He was diagnosed with the disorder in adolescence but follow-up in the outpatient setting was incomplete. Early screening and regular follow-up of patients with HHT are important to minimise the risk of development of serious sequelae, such as thromboembolic strokes and cerebral abscesses. Appropriate management demands a knowledge of the risks and benefits of asymptomatic screening and treatment in the rapidly-evolving evidence base for this disease.