National Referral Center Research Articles

Screening and management of bladder and bowel dysfunction in general pediatric outpatient clinic: a prospective observational study

BackgroundBladder and bowel dysfunction (BBD) is a common disorder in children that is often associated with psychosocial and behavioral problems. Data specific to BBD in Asian children are comparatively scarce. Accordingly, this study aimed to investigate the prevalence of BBD and the response to standard urotherapy among Thai children attending the general pediatric outpatient clinic of Siriraj Hospital – Thailand’s largest national tertiary referral center. MethodsChildren aged 4–12 years were recruited to complete the Dysfunctional Voiding Symptom Score (DVSS) questionnaire to screen for BBD during 2018 to 2020. Standard urotherapy, which consists of education and behavior management, was prescribed to those with a DVSS score that suggests the presence of BBD. Enrolled children and their caregivers were followed-up at 3 and 6 months. The Strengths and Difficulties Questionnaire (SDQ) was completed at baseline. DVSS scores at baseline, and at 3 months and 6 months after standard urotherapy were compared using repeated measures analysis of variance (ANOVA).ResultsA total of 1,042 children completed the DVSS during the study period, and 90 (8.6%) were deemed to have BBD. The mean age of BBD children was 6.9 ± 2.2 years, and the female to male ratio was 2.9:1. The most common symptoms were defecation frequency (80.0%), difficult defecation (80.0%), curtsying (74.4%), urgency (68.9%), infrequent voiding (43.3%), and daytime incontinence (32.2%). Forty-one BBD children completed the SDQ, and 32.5% had scores suggestive of hyperactivity problems. Among the 24 BBD patients who were followed-up after 3 and 6 months of standard urotherapy, there was a significant improvement in DVSS results (9.5 ± 3.1 at baseline vs. 6.9 ± 3.4 at 3 months vs. 4.4 ± 3.9 at 6 months; p < 0.01). Nine of 12 patients with urinary incontinence showed complete response at 6 months. The overall Bristol stool score significantly improved from 2.6 ± 0.7 at baseline to 3.2 ± 1.0 at 6 months (p = 0.03).ConclusionsBBD is a prevalent condition among Thai children that is often associated with emotional and behavioral problems. Standard urotherapy prescribed in a general pediatric outpatient clinic setting yielded favorable outcomes in Thai children with BBD.

Battery Ingestion in Children, an Ongoing Challenge: Recent Experience of a Tertiary Center.

IntroductionMorbidity related to childhood battery ingestions (BI) has increased recently due to the expanding use of larger lithium cells. A prompt endoscopic removal is vital to prevent severe complications in cases of esophageal batteries (EB).Materials and MethodsA retrospective, descriptive study of admissions for BI requiring endoscopic removal in a tertiary hospital's pediatric emergency department (Jan. 2011/Dec. 2020).ResultsWe had 35 cases, with an increasing incidence in the last 6 years; median age, 26 m (8 m-10 years), witnessed ingestion in 86%. On the X-ray: 14 (40%) had an EB, 21 (60%), a gastric battery (GB). Symptoms were present in 57% (100% EB/24% GB), and vomiting was the most frequent (50%). Endoscopy revealed: EB, 13 (37%); GB, 17 (49%); duodenal battery, 1 (3%); no battery, 4 (11%). Median time to removal: EB, 7 h (2 h-21days); GB, 12 h (2 h-3 days). All the patients with EB on the X-ray (14) had severe mucosal injury (Zargar classification): Grade IIIa, 7 (50%); IIIb, 5 (36%); IV, 2 (14%). CT-scan showed perforation in 2 patients (total, 4; 29% of EB). In patients with GB (21), 14 (67%) had mucosal damage; 13 (93%), mild (< Grade III, two esophageal erosions); 1 (7%) IIIa (esophageal ulceration). A statistically significant association between exposure time, younger age or battery size and severity of endoscopic lesions was found in EB location. There were no mortality cases. Acute complications occurred in 57% of EB: infection, 50%; perforation, 29%; pneumomediastinum/stridor, 14%; pneumothorax/subglottic stenosis/hemodynamic instability, 7 vs. 0% GB. Stenosis subsequently developed in 6 (43%) of EB: mild, 4 cases (29%); severe, 2 cases (14%, one resolved after endoscopic dilation; one needed a gastrostomy and esophagocoloplasty).ConclusionWe verified recent increase in admissions due to battery ingestions and associated complications, despite the availability of an emergency pediatric endoscopy team. The patients with EB had more severe mucosal injury and poorer short/long-term outcomes. Children with GB had milder lesions, although the presence of a GB did not exclude esophageal injury. The availability of actual data from national referral centers will support advocacy efforts among stakeholders, including industry representatives and policy makers, in preventing worldwide button battery injury.

Transcranial Doppler Ultrasonography in Children With Acute Liver Failure and Severe Hepatic Encephalopathy.

To report our single-center use of transcranial Doppler (TCD) for noninvasive neuromonitoring in pediatric patients with acute liver failure (ALF). Retrospective cohort from January 2016 to June 2019. PICU in Bicêtre Hospital, Assistance Publique- Hôpitaux de Paris (AP-HP), a national referral center for pediatric liver transplantation. Pediatric patients with severe ALF (prothrombin time < 30% and Hepatic Encephalopathy score ≥ 3), on continuous venovenous high-flow hemofiltration. None. Ten children were identified, six were transplanted (1/6 died) and four were not (3/4 died). TCD was performed several times per patient and the evolution of cerebral perfusion parameters was followed. Of interest, zero of six patients who survived lost end-diastolic velocity (EDV), whereas four of four patients who died did (difference, 100%; 95% CI, 37-100%; χ 2 , 9; degrees of freedom, 1; p = 0.0027). We failed to identify an association between pulsatility index (PI) or EDV, and severity of hepatic encephalopathy. TCD was a noninvasive and bedside available tool to detect and screen for presence of abnormal cerebral flow in children with ALF, according to age-related reference values. TCD detected reduced EDV and elevated PI in children with ALF awaiting transplant who died compared with those who survived.

Clinical Applicability of Patient- and Clinician-Reported Outcome Tools in the Management of Patients With Acromegaly

ObjectiveWe aimed to assess treatment outcomes and disease control status in patients with acromegaly using patient- and clinician-reported outcome tools and to analyze correlations among different components of both tools. MethodsThis cross-sectional study included 72 patients from a national referral center with a median follow-up of 8 (5-12) years. The baseline SAGIT score at diagnosis was determined retrospectively, whereas the follow-up SAGIT and acromegaly quality of life questionnaire (AcroQoL) results were assessed at the most recent visit and by additional telephone interviews. ResultsAll SAGIT subscores decreased significantly from baseline to follow-up (global score from 14 to 4 [P < .001]). The SAGIT scores at baseline did not discriminate the current disease control status. However, a higher baseline SAGIT score and subscore T were associated with uncontrolled disease after the first-line treatment. Diagnostic delay was correlated with baseline S, A, G, and global SAGIT scores. At the follow-up, the global SAGIT score discriminated between cured/controlled and uncontrolled groups (4 vs 6 [P = .007]). The AcroQoL score was 69.3, with the personal relations subscale being the least affected and the physical scale being the most affected. There was no difference in the AcroQoL score between patients classified as uncontrolled or cured/controlled. At baseline and follow-up, there were significant negative correlations between S and A subscores and AcroQoL score. A higher body mass index, the presence of swelling, joint symptoms, headaches, sleep apnea, and hypertension significantly impaired quality of life. ConclusionOur results emphasize the complementary nature of the patient- and clinician-reported outcome tools in acromegaly management. We identified modifiable signs, symptoms, and comorbidities as treatment targets that might help clinicians improve quality of life in this population.

Balloon Pulmonary Angioplasty Results in Anatomically Operable CTEPH Patients

<h3>Purpose</h3> Pulmonary endarterectomy (PEA) is the recommended treatment for patients with operable CTEPH. Balloon pulmonary angioplasty (BPA) is an emerging treatment option for inoperable patients with good preliminary results. Although deemed operable, we see more and more patients reluctant to surgery and referred to BPA. To evaluate efficacy of BPA in proximal disease, we reviewed our experience and compared results in patients who refused surgery (rPEA) to those with severe comorbidities preventing surgery (cBPA). <h3>Methods</h3> We retrospectively reviewed all CTEPH patients treated by BPA in our National Referral Center. From 2014 to 2020, 220 patients were included and assessed clinically and hemodynamically after completion of BPA treatment. Among them 36 (16%) had on angio CT a proximal disease as evaluated by our expert CTEPH multidisciplinary team: 27 (75%) were in the cBPA group and 9 in the rPEA group. <h3>Results</h3> Before BPA, pulmonary hypertension (PH) severity and the number of patients on PH targeted therapy was similar in both groups. There was no significant difference in the number of BPA sessions (6 vs. 5) and in duration of follow-up (10.7 months vs. 13.2 months) between the rPEA the cBPA groups (p=NS). Clinically, we found a significant improvement in the cBPA group (NYHA status: II vs. III; p=0.03 and 6MWT: 383 vs. 238 m; p=0.08) and not in the rPEA group (NYHA II vs. II; p=0.7 and 6MWT 409 vs. 376 m; p=0.8). Similarly, hemodynamic data improved in the cBPA group (mean PAp: 30 vs. 42 mmHg, p<0.001; CO: 5.9 min vs 4.7 L/min; p=0.1; PVR 3.3 vs 5.7 WU, p<0.001) but not in the rPEA group (mean PAp 25 vs. 35mmHg, p=0.15; CO 4.3 vs. 3.9 L/min, p=0.37; PVR 3.9 vs. 5.9 WU, p=0.18). <h3>Conclusion</h3> BPA for CTEPH patients with proximal disease is associated with better outcome in patients contraindicated to surgery because of severe comorbidities than in patients who refused PEA. When feasible, PEA remains the treatment of choice of CTEPH patients. Further prospective studies are needed to confirm these results

Understanding linkage to biopsy and treatment for breast cancer after a high-risk telemammography result in Peru: a mixed-methods study

ObjectivesThis mixed-method study aimed to understand the effectiveness of linkage to biopsy and treatment in women with a high-risk mammography result (Breast Imaging Reporting and Data System, BI-RADS 4 and...

Knowledge, Risk Perception, and Reproductive Decision Making among Women with Epilepsy

AbstractIntroduction Epilepsy is a neurological disorder that causes neurobiological, cognitive, and psychosocial consequences. Such impairments lead to substantial social influence on women across their life cycle stages, mostly connected with stigma, the severity of illness, quality of life, and other psychosocial issues in adding to reproductive decision-making associated to risk perception. This study aimed to assess the knowledge, risk perception, and reproductive decision-making factors among women with epilepsy.Materials and Methods A cross-sectional descriptive study was carried out to assess the knowledge, risk perception, and reproductive decision-making factors among women with epilepsy. A semistructured questionnaire was prepared to collect the sociodemographic and clinical characteristics of 49 women who sought treatment for epilepsy from a national tertiary referral care center for neuropsychiatry in South India. The researcher developed a 24-item questionnaire, including three open-ended questions to assess the knowledge about reproductive health issues and epilepsy.Results The participants' mean age was 24.67 ± 3.72, where 51% had secondary education, 63.3% were married, and 46.9% were homemakers. Women with epilepsy have reported lower knowledge about the illness and about the pregnancy, childbearing practices, breastfeeding, and epilepsy-related factors. Content analysis of responses to open-ended questions brought out the presence of marriage-related concerns, epilepsy and pregnancy, misconceptions about the pregnancy outcomes, and general misconceptions about the illness factors that play a role in reproductive decision-making among women living with epilepsy.Conclusion The study reveals that women with poor knowledge about epilepsy and pregnancy have difficulty in reproductive decision-making, thereby increasing risk perception of childbearing. This places interest on the necessity for health care professionals to address the above psychosocial problems as part of their intervention plan.

Preprocedural and procedural variables that predict new-onset conduction disturbances after transcatheter aortic valve replacement

BackgroundConduction disturbances are a common complication after transcatheter aortic valve replacement (TAVR). The aim of this study was to investigate the preprocedural and procedural variables that predict new-onset conduction disturbances post-TAVR (hereafter CD/CDs).MethodsConsecutive patients who underwent TAVR during December 2009–March 2021 at the Faculty of Medicine Siriraj Hospital, Mahidol University—Thailand’s largest national tertiary referral center—were enrolled. Patients with prior implantation of a cardiac device, periprocedural death, or unsuccessful procedure were excluded. Clinical and electrocardiographic data, preprocedural imaging, including membranous septum (MS) length, and procedural variables, including implantation depth (ID), were analyzed. CD was defined as new left or right bundle branch block, significant intraventricular conduction disturbance with QRS interval ≥ 120 ms, new high-grade atrioventricular block, or complete heart block. Multivariate binary logistic analysis and receiver operating characteristic (ROC) curve analysis were used to identify independent predictors and the optimal ∆MSID (difference between the MS length and ID) cutoff value, respectively.ResultsA total of 124 TAVR patients (mean age: 84.3 ± 6.3 years, 62.1% female) were included. The mean Society of Thoracic Surgeons score was 7.3%, and 85% of patients received a balloon expandable transcatheter heart valve. Thirty-five patients (28.2%) experienced a CD, and one-third of those required pacemaker implantation. The significant preprocedural and procedural factors identified from univariate analysis included intraventricular conduction delay, mitral annular calcification, MS length ≤ 6.43 mm, self-expanding device, small left ventricular cavity, and ID ≥ 6 mm. Multivariate analysis revealed MS length ≤ 6.43 mm (adjusted odds ratio [aOR] 9.54; 95% CI 2.56–35.47; p = 0.001) and ∆MSID < 0 mm (adjusted odds ratio [aOR] 10.77; 95% CI 2.86–40.62; p = < 0.001) to be independent predictors of CD. The optimal ∆MSID cutoff value for predicting conduction disturbances was less than 0 mm (area under the receiver operating characteristic curve [AuROC]: 0.896).ConclusionThis study identified MS length ≤ 6.43 mm and ∆MSID < 0 mm as independent predictors of CDs. ∆MSID < 0 was the strongest and only modifiable predictor. Importantly, we expanded the CD criteria to cover all spectrum of TAVR-related conduction injury to lower the threshold of this sole modifiable risk. The optimal ∆MSID cutoff value was < 0 mm.Trial registration: TCTR, TCTR20210818002. Registered 17 August 2021—Retrospectively registered, http://www.thaiclinicaltrials.org/show/TCTR 20210818002.

The five major autoimmune diseases increase the risk of cancer: epidemiological data from a large-scale cohort study in China.

BackgroundCancer incidence and mortality have received critical attention during the long‐term management of morbidities in patients with autoimmune diseases (AIDs). This study aimed to investigate and compare the risk of cancer associated with five major AIDs in a large‐scale Chinese cohort.MethodsA total of 8,120 AID patients consecutively admitted to a national tertiary referral center in China were included and followed‐up for 38,726.55 patient‐years, including those with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic scleroderma (SSc), and idiopathic inflammatory myositis (IIM). Demographic data, cancer incidence, predilecting sites and cancer onset time were recorded and compared among the five AIDs.ResultsFour hundred and thirty (5.3%) patients developed cancer. Their median age was 57.5 years and AID duration was 79.8 months. The estimated total standardized incidence ratio (SIR) of cancer in AIDs patients was 3.37, with the highest SIR observed in IIM (4.31), followed by RA (3.99), SSc (3.77), SS (2.88) and SLE (2.58). The increased SIR of cancers in AID patients showed a female predominance (female vs. male: 3.59 vs. 2.77) and younger patient involvement (age <50 vs. ≥50 years: 4.88 vs. 3.04). Patients with SLE had increased SIRs for developing hematologic malignancies and solid tumors located in the urinary bladder, corpus uteri and cervix uteri. Patients with SS had a significantly high SIR for developing non‐Hodgkin's lymphoma. Within 3 years of IIM diagnosis, 74.6% of the patients developed cancer and they had a high risk of ovarian cancer. RA was associated with a wide distribution of scancers, including non‐Hodgkin's lymphoma, gynecologic, urinary tract, thyroid gland and lung cancers. SSc patients had increased SIRs for developing cervical uterine, lung, and breast cancers.ConclusionPatients with five major AIDs in China had an increased risk of developing cancer, with a predominance in women and younger patients, although cancer incidence, predilection sites and cancer onset time may vary greatly in each AID entity.

Robotic retroperitoneal lymph node dissection for testicular cancer at a national referral centre.

ObjectivesWe aim to determine if robot‐assisted retroperitoneal lymph node dissection (R‐RPLND) can be performed as a safe option to open RPLND in selected patients with metastatic germ cell cancer.Patients and methodsThis population‐based prospective study was performed at a one of two national referral centres for RPLND in Sweden. All patients referred during January 2017–March 2021 were screened for possible inclusion. R‐RPLND was performed using the Da Vinci Xi surgical system. Perioperative parameters, postoperative complications (Clavien–Dindo), final pathology, preservation of antegrade ejaculation and relapse rates were evaluated. Classifiers for selecting patients to open versus robotic RPLND were analysed by logistic regression modelling. The median follow‐up was 23 months.ResultsOf 87 patients referred, 29 were selected for R‐RPLND, 19 in a post‐chemotherapy setting. In median, retroperitoneal tumour diameter was 18 mm, BMI 24 kg/m2, operative time 433 min, estimated blood loss 50 ml and length of stay 3 days. One patient underwent open conversion due to failure to progress. Four patients had Clavien–Dindo grade 3 complications, of which three were chylous‐related. No in‐field recurrences occurred during follow‐up.ConclusionThis population‐based study suggests that R‐RPLND can be safely performed in at least one third of patients referred for an RPLND. A relatively high rate of lymph‐leakage may represent a potential drawback. Tumour size may be the most important discriminator when deciding on robotic versus open RPLND. Further studies with longer follow‐up are needed to validate the results.

Characterization of the Portuguese population diagnosed with retinoblastoma

The purpose of this study is to characterize demographically and genetically the Portuguese population with retinoblastoma; to report the clinical stage at presentation and its impact on survival and ocular preservation rate and, finally, to assess the incidence of retinoblastoma in Portugal. Retrospective observational study including children consecutively diagnosed with retinoblastoma at the Portuguese National Referral Center of Intraocular Tumors, between October 2015 and October 2020. Twenty-eight children were diagnosed with retinoblastoma at our center, 15 hereditary from which 12 presented with bilateral retinoblastoma and 3 were unilateral. The overall mean age at diagnosis was 13.6 ± 11.1 months with hereditary retinoblastomas diagnosed slightly earlier at 9.6 ± 6.3 months. A familial history of retinoblastoma was found in only 4 (14.3%) of the cases. A pathogenic mutation in the RB1 gene was found in 13 (46.4%) of the children. The most frequent sign at referral was leukocoria in 71.4% of patients. Considering the ICRB classification of the tumors, 84.6% of non-hereditable hereditary retinoblastomas were referred to our center in advanced stages. In the group of hereditable retinoblastomas 86.7% presented with one of the eyes with advanced intraocular retinoblastoma. Fourteen children had one eye enucleated due to retinoblastoma. No deaths were registered during the study period. Considering the incidence analysis, we registered a year-of-birth controlled incidence analysis of 4.04 per 100.000 living births (IC 95% 1.59–6.49). This is the first characterization of the Portuguese Population diagnosed with Retinoblastoma in the National Reference Center.

Anticoagulants decrease the risk for catheter-related venous thrombosis in patients with chronic intestinal failure: A long-term cohort study.

BackgroundCatheter‐related venous thrombosis (CRVT) is a severe complication of home parental nutrition. Although primary prevention of CRVT is crucial, there is no consensus on anticoagulant use to prevent this adversity. The aim was to compare CRVT risk in patients with chronic intestinal failure (CIF) in the presence or absence of anticoagulants, and to identify CRVT risk factors.MethodsThis retrospective cohort study comprised adult patients with CIF with a central venous access device (CVAD) between 2010 and 2020 that were treated at our national CIF referral center. Analyses were performed at a CVAD level.ResultsOverall, 1188 CVADs in 389 patients were included (540.800 CVAD days). Anticoagulants were used in 403 CVADs. In total, 137 CRVTs occurred in 98 patients, resulting in 0.25 CRVTs/1000 CVAD days (95% CI, 0.22–0.29). Anticoagulant use was associated with a decreased CRVT risk (odds ratio [OR] = 0.53; 95% CI, 0.31–0.89; P = 0.02). Left‐sided CVAD insertion (OR = 2.00; 95% CI, 1.36–2.94), a history of venous thrombosis (OR = 1.73; 95% CI, 1.05–2.84), and a shorter period postinsertion (OR = 0.78; 95% CI, 0.65–0.92) were independently associated with an increased CRVT risk.ConclusionAnticoagulants decreased the CRVT risk. In addition, we identified left‐sided vein insertion, a history of venous thrombosis, and a shorter period post‐CVAD insertion as CRVT risk factors. Further prospective studies should provide guidance whether prophylactic anticoagulant use, especially in higher‐risk patients with a left‐sided CVAD or a history of venous thrombosis, is justified.

Efficacy of cidofovir versus bevacizumab in recurrent respiratory papillomatosis: A randomized, double-blind, placebo-controlled pilot study

ObjectivesAfter surgical resection of papilloma, adjuvant therapy may be recommended for the control of recurrent respiratory papillomatosis (RRP). As the efficacy of adjuvant therapy remains unproven, the aim of this study was to compare the efficacy of cidofovir versus bevacizumab used as adjuvant therapies for the control of RRP. MethodsThis randomized, double-blind, placebo-controlled pilot study was performed in a national respiratory disease referral centre. Patients with RRP were recruited prospectively and were divided into juvenile or adult RRP. Participants were randomly assigned to receive adjuvant therapy with cidofovir, bevacizumab or placebo. The study drug or placebo was administered after direct microlaryngoscopy with papilloma resection using cold instruments. The Derkay severity score and the Voice Handicap Index (VHI) were assessed at 3–6-week intervals, for a total of 3 visits. Follow-up included VHI and Derkay score assessments at 2-month intervals over the course of one year. Annual rates before and after surgical treatment were compared. ResultsFive children and 11 adults were enrolled in the study. After one year, the group treated with cidofovir had a significant decrease in Derkay score (p=.027). No difference between treatment arms was observed in the annual surgery rate. There was a significant decrease in the VHI score in all treatment groups (p<.001), and no significant difference was observed between groups (p=.32). ConclusionWhile we observed a significant decrease in RRP severity with intralesional cidofovir, we were unable to provide proof of efficacy of intralesional bevacizumab.Clinicaltrials.gov Identifier: NCT02555800.

Naturalistic Study of Depression Associated with Parkinson's Disease in a National Public Neurological Referral Center in Mexico.

Major depressive disorder (MDD) is a major health problem in Parkinson’s disease (PD) patients. We described the clinical and sociodemographic factors of MDD among patients with PD at a national neurological referral center in Mexico. One hundred patients with PD + MDD were included in the study. All the patients were evaluated during the “ON” treatment phase of PD. Clinical scales for cognition (MMSE and MoCA) and MDD (MADRS) were applied. The mean age was 58.49 ± 11.02 years, and 57% of the sample was male. The most frequent symptom of PD was tremor (67%), and onset was more frequent on the right side (57%). Additionally, 49% of the patients with PD had moderate to severe (M/S) MDD. Selective serotonin reuptake inhibitors were the most frequent antidepressant treatment (69%). The scores of the scales were MADRS 21.33 ± 5.49, MoCA 21.06 ± 4.65, and MMSE 26.67 ± 1.20. The females had lower MMSE scores compared to the males (p = 0.043). The patients with M/S MDD had more rigidity at the beginning of PD (p = 0.005), fewer march alterations (p = 0.023), and a greater prevalence of left-side initial disease (p = 0.037). Rigidity was associated with M/S MDD (OR 3.75 p = 0.013). MDD was slightly more frequent in the males than in the females. The MDD symptoms and cognitive impairment were worse in the female population.

Risk Factors for Severe COVID-19 and Hospital Admission in Patients With Inborn Errors of Immunity - Results From a Multicenter Nationwide Study.

Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44–3.53) risk ratio for hospital admission and a higher mortality ratio (2.4% vs. 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico.

To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/μL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Abstract P1-07-08: Endoxifen predicts early recurrence in breast cancer: A Brazilian prospective study

Abstract Tamoxifen is widely used in adjuvant therapy for breast cancer patients, but up to one-third of patients recur within 15 years after surgery even with its regular use. Low plasma levels of (Z)-endoxifen, the most active tamoxifen metabolite, have been studied as a possible predictor of treatment failure. Here, we evaluated plasma (Z)-endoxifen as a predictor of response to adjuvant treatment in breast cancer patients. Methods: One hundred forty nine patients were selected from a prospective cohort of consecutive newly diagnosed breast cancer patients recruited at a national referral center for treatment of cancer in Curitiba, Southern Brazil. Inclusion criteria were breast cancer women on stage I - III, positive hormone receptor tumors, operable, undergoing or not (neo)adjuvant chemotherapy, and signed for adjuvant tamoxifen for at least five years. At diagnosis, peripheral blood samples were collected for CYP2D6 genotyping for *1 *2, *3, *4, *5, *6, *7, *8, *9, *10, *17, *29 and *41 and subsequent metabolic activity scores according to phenotypes assigned for each allele (poor metabolizer PM; intermediate, IM; extensive, EM and ultrarapid metabolizer, UM). After the tamoxifen initiation, patients were evaluated at months 3, 6, and 12 for adherence and drug interactions, and plasma (Z)-endoxifen quantification. They were followed from April 2014 to April 2019. The study's primary objective was to evaluate whether (Z)-endoxifen plasma levels predict early recurrence in patients on adjuvant tamoxifen. The secondary aim was to evaluate an association between (Z)-endoxifen levels and clinical and phenotypic CYP2D6 metabolism variables. A Cox model estimated hazard ratios (HR) comparing recurrence free survival (RFS) according to (Z)-endoxifen plasma levels. The survival was compared using the Kaplan-Meier method and the log-rank test. Results: The median follow-up period was 52.3 months and at that point, there were 20 recurrences of 149 patients. At 3 months there were no cases of low adherence to tamoxifen. The (Z)-endoxifen levels were established by quartiles, with the first lower quartile being used as a cutoff (14.72nM). High (Z)-endoxifen levels at 3 months (&amp;gt;14.72nM) were detected in 75.8% (n = 113) of cases and low levels (≤14.72nM) in 24.2% (n = 36). There was no statistically significant difference between the groups with low or high (Z)-endoxifen levels regarding clinical and pathological variables, but there was a higher CYP2D6 PM/IM frequency in the low (Z)-endoxifen levels group (p&amp;lt;0.001). High (Z)-endoxifen levels were associated with lower RFS compared to low (Z)-endoxifen levels (HR 2.5, 95% CI 1.00-6.22, p=0.041). Low (Z)-endoxifen levels increased the recurrence risk even when adjusted for staging and molecular subtypes (HR 2.55, 95% CI 1.00-6.48, p&amp;lt;0.001) or staging and CYP2D6 phenotype (UM/EM vs IM/PM; HR 4.38, 95% CI 1.66-11.59, p=0.003), or prior chemotherapy exposure (HR 2.65, 95% CI 1.06-6.61, p=0.036). Conclusion: This is the first Brazilian prospective trial evaluating the association of plasma (Z)-endoxifen levels, with the clinical outcome in breast cancer women treated with adjuvant tamoxifen, controlled by predictable confounding factors of plasma (Z)-endoxifen levels, such as tamoxifen adherence, and drug interaction with CYP2D6 inhibitors. In our study, a low plasma level of (Z)-endoxifen (≤ 14.72nM) after 3 months of tamoxifen treatment was a predictor of early recurrence in patients under adjuvant tamoxifen (p=0.041). A longer follow-up and a larger cohort may be needed to confirm the (Z)-endoxifen cutoff value that is a predictor of long-term recurrence. Citation Format: Thais Almeida, Werner Schroth, Jeanine Marie Nardin, Thomas Mürdter, Solane Picolotto, Reiner Hoppe, Jenifer Primon Kogin, Elisa Daniele Gaio, Angela Dasenbrock, Raquel Cristina Skrsypcsak, Lucia Noronha, Hiltrud Brauch, José Claudio Casali-da-Rocha. Endoxifen predicts early recurrence in breast cancer: A Brazilian prospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-07-08.

Amyloidosis from the patient perspective: the French daily impact of amyloidosis study

Background Amyloidosis is a complex group of rare conditions. For patients, amyloidosis is severely debilitating: physically and psychologically. Currently, data are lacking to evaluate the medical, economic, and social burden of systemic amyloidosis. Objective To analyse the patient burden according to the main types of systemic amyloidosis. Methods The French Daily Impact of Amyloidosis study was an observational, cross-sectional and non-interventional study. Adults diagnosed with light chain (AL), transthyretin (ATTR), amyloid A (AA) and other rare forms of amyloidosis were eligible. Data regarding amyloidosis prevalence, diagnosis, management, and impact on everyday life were collected using a study-specific survey built by the Association Française Contre l’Amylose (AFCA) and the four French National Referral Centres for Amyloidosis. Results A total of 603 patients, predominantly male (65%) with an average age of 66.8 years, including 170 AL, 224 ATTRv, 109 ATTRwt and 25 AA amyloidosis patients, completed the study-specific survey. The median delay from presentation to confirmed diagnosis was 27.4 months but varied according to amyloidosis type. Patients before diagnosis had breathlessness (49%), tingling sensation (33%), pain (28%), difficulty in walking (28%) and weight loss (22%). Amyloidosis was most frequently suspected (49%) and confirmed (57%) in local hospitals but managed in French amyloidosis referral centres (58%). Patients often reported problems with mobility, usual activities, pain/discomfort and anxiety/depression, but not with self-care. Conclusions Systemic amyloidosis severely impacts daily life. The delay to confirmed amyloidosis diagnosis needs to be reduced. Early, effective treatment is required to optimise patient benefits.

Reimagining leprosy elimination with AI analysis of a combination of skin lesion images with demographic and clinical data

Leprosy is an infectious disease that mostly affects underserved populations. Although it has been largely eliminated, still about 200'000 new patients are diagnosed annually. In the absence of a diagnostic test, clinical diagnosis is often delayed, potentially leading to irreversible neurological damage and its resulting stigma, as well as continued transmission. Accelerating diagnosis could significantly contribute to advancing global leprosy elimination. Digital and Artificial Intelligence (AI) driven technology has shown potential to augment health workers abilities in making faster and more accurate diagnosis, especially when using images such as in the fields of dermatology or ophthalmology. That made us start the quest for an AI-driven diagnosis assistant for leprosy, based on skin images. Here we describe the accuracy of an AI-enabled image-based diagnosis assistant for leprosy, called AI4Leprosy, based on a combination of skin images and clinical data, collected following a standardized process. In a Brazilian leprosy national referral center, 222 patients with leprosy or other dermatological conditions were included, and the 1229 collected skin images and 585 sets of metadata are stored in an open-source dataset for other researchers to exploit. We used this dataset to test whether a CNN-based AI algorithm could contribute to leprosy diagnosis and employed three AI models, testing images and metadata both independently and in combination. AI modeling indicated that the most important clinical signs are thermal sensitivity loss, nodules and papules, feet paresthesia, number of lesions and gender, but also scaling surface and pruritus that were negatively associated with leprosy. Using elastic-net logistic regression provided a high classification accuracy (90%) and an area under curve (AUC) of 96.46% for leprosy diagnosis. Future validation of these models is underway, gathering larger datasets from populations of different skin types and collecting images with smartphone cameras to mimic real world settings. We hope that the results of our research will lead to clinical solutions that help accelerate global leprosy elimination. This study was partially funded by Novartis Foundation and Microsoft (in-kind contribution).

Italian Cystic Fibrosis Registry (ICFR). Report 2019-2020

Italian Cystic Fibrosis Registry (ICFR). Report 2019-2020