Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.

Clinical characteristics and outcomes of COVID-19 patients in a tertiary hospital in Baguio City, Philippines.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily targets the respiratory system. This study describes the characteristics associated with mortality among patients infected with SARS-CoV-2 at a single hospital in Baguio City, Philippines. METHODS: We reviewed medical records (including history, laboratory results and treatment regimen) of 280 confirmed COVID-19 patients admitted to a single hospital during March-October 2020. Clinical characteristics and outcomes (frequency and type of complication, recovery rate and mortality) were evaluated. Multiple logistic regression was used to analyse factors associated with mortality. RESULTS: The mean age of COVID-19 patients was 48.4 years and the female-to-male ratio was 1.8:1. Hypertension, cardiovascular disease (CVD) and diabetes were the most frequent comorbidities reported. Common presenting symptoms were respiratory and constitutional, with 41% of patients not reporting symptoms on admission. Patients with moderate, severe and critical disease comprised 45%, 8% and 4%, respectively. A total of 15% had complications, health care-associated pneumonia being the most frequent complication. The recovery rate was 95%; 5% of patients died, with multiorgan failure being the most common cause. The presence of CVD, chronic kidney disease, prolonged prothrombin time and elevated lactate dehydrogenase (LDH) were associated with mortality. DISCUSSION: Most COVID-19 patients in our population had asymptomatic to moderate disease on admission. Mortality from COVID-19 was associated with having CVD, chronic kidney disease, elevated LDH and prolonged prothrombin time. Based on these results, we emphasize that people should take all necessary precautions to avoid infection with SARS-CoV-2.

MRI of endolymphatic hydrops in patients with intralabyrinthine schwannomas: a case-controlled study using non-enhanced T2-weighted images at 3 T.

OBJECTIVE: Like other vestibular schwannomas developing in the internal auditory canal, intralabyrinthine schwannomas (ILS) may present with similar symptoms as in endolymphatic hydrops. Two different studies have described MR saccular hydrops in ~ 30% of internal auditory canal vestibular schwannomas, but this association has never been studied in ILS before. The aim of this work is to study the prevalence of a saccular dilation in ILS, on a T2-weigthed sequence at 3 T, compared to a control group. MATERIAL AND METHODS: All patients presenting with typical ILS between January 2008 and October 2018 were included (n = 28, two patients with bilateral tumors) and compared to a control group (n = 53). All underwent a high-resolution T2-weighted 3D sequence (FIESTA-C). The height and width of the saccule were measured on a coronal plane by two radiologists. RESULTS: The saccule was dilated on the side of the schwannoma in 47% of the cases (p = 0.0006 for the height, p = 0.0487 for the width). Bilateral saccular dilation was observed in 37% of the cases. There was a statistically significant correlation between the presence of a saccular hydrops and balance disorders (p = 0.02) as 50% of the patients with an intralabyrinthine schwannoma who presented with such symptoms had a saccular dilation. CONCLUSION: Forty-seven percent of ILS are associated with homolateral saccular dilation, which is an MR sign of endolymphatic hydrops (bilateral in 37%) and it appears related to the presence of balance disorders. This opens new therapeutic potentialities with the possible use of anti-vertiginous drugs, which could have a beneficial effect on their clinical symptomatology.

CT and MRI for the diagnosis of perilymphatic fistula: a study of 17 surgically confirmed patients.

BACKGROUND: We evaluated the usefulness of CT and MRI for the diagnosis of perilymphatic fistula (PLF) of the round (RW) and/or oval (OW) windows, with surgery as gold standard. METHODS: We retrospectively enrolled 17 patients who presented a surgically confirmed PLF of the round (RW) or oval (OW) windows. All patients were imaged by CT + MRI (T2W SSFP without contrast) prior to surgery (= gold standard). Two radiologists, analyzed the RW and OW on the side of the clinical symptoms and sensitivity (Se) + Specificity (Sp) were calculated. RESULTS: Round window fistula was the most frequent (71%). The best sign of PLF on imaging was a fluid filling of the window niches, which had good Se (83-100% for RW, 66-83% for OW) and Sp (60% for RW, 91-100% for OW). Disorientation of the footplate and pneumolabyrinth were also only observed in 50% of OW PLF. CONCLUSION: The combination of CT and MRI is a reliable tool for a fast and accurate diagnosis of round and oval window perilymphatic fistula, with good sensitivity (> 80%). The most common sign of PLF on imaging is the presence of a fluid-filling in the RW (especially if > 2/3 of the RW niche) or in the OW niches on both CT and MRI. A disorientation of the footplate or the presence of a pneumolabyrinth are clearly in favor of an oval window perilymphatic fistula.

MRI of endolymphatic hydrops in patients with vestibular schwannomas: a case-controlled study using non-enhanced T2-weighted images at 3 Teslas.

OBJECTIVE: Vestibular schwannomas (VS) may present with similar symptoms endolymphatic hydrops. Association between hydrops and internal auditory canal VS has been described by Naganawa et al. (Neuroradiology 53:1009-1015, 2011), but has never been confirmed since. The aim of this work was to study the prevalence of a saccular dilation on a T2-weighted sequence at 3 T MRI in VS compared to a control group. MATERIALS AND METHODS: All patients presenting with typical VS between May 2009 and July 2018 were included (n = 183) and compared to a control group (n = 53). All underwent a high-resolution T2-weighted 3D sequence (FIESTA-C). The height and width of the saccule were measured on a coronal plane by two radiologists. RESULTS: The saccule was dilated on the side of the schwannoma in 28% of the cases (p = 2.81 × 10- 5), with 15.7% of bilateral dilation. Saccular dilation was correlated to sensorineural hearing loss (OR 3.26, p = 0.02). There was also a significant correlation between saccular hydrops on the normal contralateral side of patients with VS and vertigo (p = 0.049), and between saccular hydrops on the side of the tumour and tinnitus (p = 0.006). CONCLUSION: A third (29%) of VS are associated with a saccular dilation on the side of the tumour, which is an MR sign of endolymphatic hydrops (bilateral in 15.7% of the cases) and it appears related to sensorineural hearing loss and tinnitus, as well as vertigo if a contralateral dilation is present. This opens new therapeutic potentialities with the use of anti-vertiginous drugs, which could have a beneficial effect on the clinical symptoms.

Is an Intravenous Injection of Gadolinium Really Necessary for Intralabyrinthine Schwannomas MR Examination?

OBJECTIVES: Our aim was to confirm the usefulness of T2-weighted (T2W) gradient-echo sequence for detection and topographic diagnosis of intralabyrinthine schwannomas (ILS) compared with T1W contrast-enhanced sequence as gold standard, to evaluate the necessity of intravenous gadolinium injection for ILS follow-up imaging. METHODS: Thirty patients with ILS were retrospectively enrolled and compared to a control group of 30 patients with no inner ear pathology. All patients underwent a T2W gradient-echo steady-state free precession (SSFP) acquisition at 3T, which was visually analyzed by two radiologists and compared to contrast-enhanced T1W sequence. A quantitative analysis was also performed, with the measurement of the tumor and inner ear signal on T2W images and the measurement of the tumor length in cochlear schwannomas. RESULTS: T2W FIESTA-C sequence correctly diagnosed ILS with a sensitivity (Se) of 95% and a specificity (Sp) of 100%, with matching results for their topographic evaluation (Se 92%, Sp 98%) compared with the gold-standard. The difference between the two sequences was only 2.5%, with excellent interobserver agreement. The tumor signal on T2W images was significantly lower than the normal bright signal of the normal inner ear fluids (mean signal ratio = 0.42 vs 0.98). CONCLUSION: The positive and topographic diagnostic accuracy of T2W FIESTA-C sequence was excellent compared with the T1W contrast-enhanced sequence, even though the latter remains easier and faster to analyze for an untrained radiologist. The performances of T2W gradient-echo sequence at 3T make it a reasonable alternative strategy for following ILS after they are diagnosed.

Does the Feldenkrais Method make a difference? An investigation into the use of outcome measurement tools for evaluating changes in clients.

Evidence-based practice confirms the need for outcome measures. Feldenkrais Method practitioners struggle to use such tools because of the broad range of applications of the Feldenkrais Method and the difficulty identifying suitable measurement tools. A pre/post-test design was used to investigate the use of three outcome measurement tools [Patient-specific Functional Scale (PSFS), Pain Outcome Profile (POP) and Short Form12v2 Health questionnaire (SF12v2)] for clients experiencing problems performing everyday functional tasks who attended Feldenkrais sessions. Eleven Feldenkrais practitioners submitted data on 48 clients. Changes were detected in the clients' ability to perform everyday tasks (PSFS improved 3.8 points, p < 0.001), levels of pain decreased (POP improved in current pain p = 0.001, physical index p < 0.001 and affective index p = 0.001) and quality of life improved significantly in six of the eight SF12v2 domains. These three tools have been found to be suitable for detecting changes in client function before and after a series of Feldenkrais sessions.