Symptoms In Period Research Articles

Patient-Reported Symptom and Functioning Status during the First 12 Months after Chimeric Antigen Receptor T Cell Therapy for Hematologic Malignancies

Chimeric antigen receptor (CAR) T cell therapy is being increasingly used to treat patients with advanced hematologic malignancies; however, the symptoms related to standard of care CAR T cell therapy during the first year after treatment have not been assessed using patient-reported outcome (PRO) measurements. This study aimed to quantify patients' perspectives of symptom burden and functional status using PROs during the first year after CAR T cell therapy for hematologic malignancies, especially in patients who experienced grade 2-4 toxicities. Sixty patients were enrolled in this observational cross-sectional study at any time during their first 12 months post-treatment. All 60 had received CAR T cell therapy as standard of care at MD Anderson Cancer Center in 2019. PROs were measured using the MD Anderson Symptom Inventory (MDASI), the PROs Measurement Information System 29 (PROMIS-29), the global health tool EQ5D-5L, and the single-item health-related quality of life scale (HRQoL). Twenty-two additional symptoms related to CAR T cell therapy, as identified by an expert panel, were also evaluated. CAR T cell therapy-related toxicities were rated according to the ASTCT consensus grading criteria. The majority of patients (52 of 60; 87%) received axicabtagene ciloleucel (Yescarta). One-third of the patients developed grade 2-4 cytokine release syndrome or neurotoxicity. The first 90 days after infusion represented the most symptomatic period, in which >10% of patients rated 18 symptoms as severe (ie, MDASI symptom score of 7 to 10 on scale of 0 to 10), strongly indicating the need for effective symptom management. Physical functioning, measured by interference on the "general activity" item on the MDASI and this domain on the PROMIS-29, were significantly worse in patients who underwent therapy during the first 30 days compared with those who underwent therapy over 90 days (all P < .05 with the Hochberg step-up procedure), whereas the EQ5D-5L and single-item HRQoL did not detect such differences. Compared with patients who had mild cytokine release syndrome or neurotoxicity (grade 0-1), patients who developed grade 2-4 toxicities persistently reported multiple severe symptoms after 30 days following therapy (all P < .05). Furthermore, although using a different recall period, patient-reported scores on several PROMIS-29 domains were significantly correlated with the scores of corresponding MDASI symptom items. This real-world quantitative PRO symptoms study provides evidence of unique profiles of the physical, psychological, and cognitive symptom burden in patients undergoing CAR T cell therapy that varies within the first year after infusion and demonstrates differences among PRO measurement scales. These results support the need for validation of fit-for-purpose PRO measurements for routinely monitoring symptom and toxicity burdens in CAR T cell therapy care settings.

Factors associated with length of stay and treatment outcome of Ebola patients treated at an Ebola treatment center in Sierra Leone during the peak period of the West African Ebola outbreak 2013\u20132016

BackgroundThe World Health Organization (WHO) declared the West Africa Ebola epidemic as a Public Health Emergency of International Concern in August 2014. During the outbreak period, there were calls for the affected countries to construct Ebola treatment centres and reliable diagnostic laboratories closer to areas of transmission in order to improve the quality care of Ebola Virus Disease (EVD) patients. Delay in seeking treatment has been reported to have led to poor treatment outcome of EVD patients. Sierra Leone recorded more than 8000 probable and confirmed cases and more than 4000 EVD -related deaths nation-wide.MethodsIn this retrospective study, we investigated the effects of treatment delay, length of symptomatic period, EVD patients’ sex, age, occupation, region of residence, and clinical characteristics on the treatment outcome of 205 laboratory-confirmed EVD patients who were admitted at the Kenema Government Hospital Ebola Treatment Center (KGHETC) from 13/09/2014–26/11/2014; i.e. during the peak of 2013–2016 EVD outbreak in Sierra Leone. Specifically also, we determined the factors that were associated with the length of stay for EVD treatment for patients who were discharged alive.ResultsMajority (66.3%, n = 205/309) of the 309 suspected EVD patients with medical records at the KGHETC triage during the period under review were tested positive for EVD using reverse-transcriptase-polymerase chain reaction (RT-PCR) and had a definitive treatment outcome. Few (33.7%, n = 104/309) suspected EVD patients were not included in our analysis and were classified thus: 29.1% (n = 90/309) suspect EVD cases with negative RT-PCR results, 4.5% (n = 14/309) suspect cases with non-available RT-PCR result.Of the 205 patients, 99 (48.3%) had a fatal outcome. For EVD patients that survived, we recorded a significant association (− 0.06, 95% Confidence Interval (CI) = − 0.14 – - 0.02, p = 0.004) between the Length of Stay (LOS) and for each kilometer travelled to seek treatment at the KGHETC. However, the association between EVD patients that were low skilled workers (− 5.91, 95% CI = − 24.60 – 12.79, p = 0.73), EVD patients who were children and pupils in junior school (− 0.86, 95% CI = − 12.86 – 11.14, p = 0.73), health seeking delay for EVD patients who resided in Kenema District where the KGHETC was located (− 0.49, 95% CI = − 0.12 – 1.09, p = 0.24), sex (− 1.77, 95% CI = − 8.75 – 5.21, p = 0.50), age (0.21, 95% CI = − 0.36 – 0.77, p = 0.57), referral status (1.21, 95% CI = − 17.67 – 20.09, p = 0.89) and the LOS in surviving patients were not statistically significant.ConclusionThe high LOS for either treatment outcome for EVD patients that resided in the district in which the EVD treatment facility was located compared to those patients from other districts implies that health authorities should consider intensive health education with high priority given to seeking early EVD treatment, and the construction of strategic ETCs as important components in their response strategy.

Posterior reversible encephalopathy syndrome during management of hematological disorders

Background Posterior reversible encephalopathy syndrome (PRES) is a disorder of reversible subcortical vasogenic brain edema with acute neurological symptoms. Diagnosis of PRES is based on exclusion, and treatment consists of symptomatic management. Aims To study the clinical features, radiological findings, and outcomes of PRES in patients with hematological disorders. Patients and methods Case files of patients diagnosed with PRES from January 2016 to November 2019 were reviewed. PRES was diagnosed based on clinical features and MRI findings. Primary diagnosis, clinical history, vital signs, laboratory parameters, treatment summary, and neuroimaging findings were recorded. Results A total of 16 patients were diagnosed with PRES. Their median age was 7 years (range, 2–25 years). A total of 12 patients had acute lymphoblastic leukemia, who were on induction phase, two patients had aplastic anemia, and one each had acute myeloid leukemia and beta-thalassemia major. All patients had hypertension and 15 had seizures as initial presentation of PRES. Overall, 12 patients had bilateral subcortical white matter hyperintensity on T2 in occipital and parietal lobes on MRI. All patient recovered, except one, who had residual neurological deficit. All patients were restarted on the disease therapy once the patients were stabilized. No recurrences were observed. Conclusion Early recognition of PRES may help initiate timely treatment and reduce morbidity and mortality. Implicating agents may be withheld during the symptomatic period. Its management is symptomatic, and therapy may be restarted once patient is clinically stable. Its prognosis is favorable, but some patients may have residual neurological deficit.

Evidence of altered interhemispheric communication after pediatric concussion

ABSTRACT OBJECTIVES: To investigate neurophysiological alterations within the typical symptomatic period after concussion (1-month) and throughout recovery (6-months) in adolescents; and (2) to examine relationships between neurophysiological and upper limb kinematic outcomes. METHODS: 18 adolescents with concussion were compared to 17 healthy controls. Transcranial magnetic stimulation (TMS) was used to assess neurophysiological differences between groups including: short- and long-interval intracortical inhibition, intracortical facilitation, short- and long-latency afferent inhibition, afferent facilitation, and transcallosal inhibition (TCI). Behavioral measures of upper limb kinematics were assessed with a robotic device. RESULTS: Mixed model analysis of neurophysiological data identified two key findings. First, participants with concussion demonstrated delayed onset of interhemispheric inhibition, as indexed by TCI, compared to healthy controls. Second, our exploratory analysis indicated that the magnitude of TCI onset delay in adolescents with concussion was related to upper limb kinematics. CONCLUSIONS: Our findings indicate that concussion in adolescence alters interhemispheric communication. We note relationships between neurophysiological and kinematic data, suggesting an affinity for individuals with less concussion-related physiological change to improve their motor behavior over time. These data serve as an important step in future development of assessments (neurobiological and clinical) and interventions for concussion.

Impending cauda equina syndrome due to Kummell disease; A case report and literature review.

IntroductionKummell disease (KD) is a rare cause of vertebral fracture due to osteonecrosis. The natural history of the disease is characterized by a previous minor trauma, a subclinical window period, and then a symptomatic period presenting with disabling pain, kyphosis, or neurologic deficit.ImportanceAs an important but rare cause of non-discogenic cauda equina syndrome.Case presentationHere, we report on a wheelchair-bound 28-years-old bodybuilder man with KD who presented with progressive paresthesia and weakness of both legs (impending cauda equina syndrome) due to L5 involvement. He had a past medical history of arbitrary use of licensed and unlicensed drugs in the fitness field. The patient underwent posterior decompression, spinopelvic stabilization, and fusion. Postoperative rehabilitation was satisfactory and after six months, the leg muscle strength returned to normal and the patient's back pain disappeared.ConclusionKD should be considered as a rare differential diagnosis when dealing with any patient with a vertebral fracture associated with a history of minor trauma and an asymptomatic window period.

Diagnostic Performance of Ag-RDTs and NAAT for SARS-CoV2 Identification in Symptomatic Patients in Catalonia.

The use of rapid antigenic tests (Ag-RDTs) to diagnose a SARS-CoV-2 infection has become a common practice recently. This study aimed to evaluate performance of Abbott PanbioTM Ag-RDTs with regard to nucleic acid amplification testing (NAAT) in the early stages of the disease. A cohort of 149,026 infected symptomatic patients, reported in Catalonia from November 2020 to January 2021, was selected. The positivity rates of the two tests were compared with respect to the dates of symptom onset. Ag-RDTs presented positivity rates of 84% in the transmission phases of the disease and 31% in the pre-symptomatic period, compared to 93% and 91%, respectively, for NAAT. The detection of many false negatives with Ag-RDTs during the pre-symptomatic period demonstrates the risk of virus dissemination with this diagnostic technique if used outside the symptomatic period.

Hypoglycemic attacks and growth failure are the most common manifestations of citrin deficiency after 1 year of age.

Citrin deficiency develops in different symptomatic periods from the neonatal period to adulthood. Some infantile patients are diagnosed by newborn mass screening or symptoms of neonatal intrahepatic cholestasis caused by citrin deficiency, some patients in childhood may develop hepatopathy or dyslipidemia as failure to thrive and dyslipidemia caused by citrin deficiency, and some adults are diagnosed after developing adult-onset type 2 citrullinemia (CTLN2) with hyperammonemia or encephalopathy. A diagnosis is needed before the development of severe phenotypic CTLN2 but is often difficult to obtain because newborn mass screening cannot detect all patients with citrin deficiency, and undiagnosed patients often appear healthy in childhood. There are only a few reports that have described patients in childhood. To explore the clinical features of undiagnosed patients with citrin deficiency in childhood, we studied 20 patients who were diagnosed after the first year of life. Of these patients, 45% experienced hypoglycemic attacks in childhood. The acetoacetic acid level during hypoglycemic attacks was lower than expected. Growth failure at diagnosis (45%) was also noted. From the patients' history, fat- and protein-rich food preferences (80%), a low birth weight (70%), and prolonged jaundice or infantile hepatopathy (40%) were identified. To diagnose citrin deficiency in childhood, we should ask about food preferences and a history of infantile hepatopathy for all children with severe hypoglycemia or growth failure and consider the genetic test for citrin deficiency if the patient has characteristic food preferences or a history of infantile hepatopathy.

Diagnostic accuracy of two commercial SARS-CoV-2 antigen-detecting rapid tests at the point of care in community-based testing centers.

ObjectivesDetermine the diagnostic accuracy of two antigen-detecting rapid diagnostic tests (Ag-RDT) for SARS-CoV-2 at the point of care and define individuals’ characteristics providing best performance.MethodsWe performed a prospective, single-center, point of care validation of two Ag-RDT in comparison to RT-PCR on nasopharyngeal swabs.ResultsBetween October 9th and 23rd, 2020, 1064 participants were enrolled. The PanbioTM Covid-19 Ag Rapid Test device (Abbott) was validated in 535 participants, with 106 positive Ag-RDT results out of 124 positive RT-PCR individuals, yielding a sensitivity of 85.5% (95% CI: 78.0–91.2). Specificity was 100.0% (95% CI: 99.1–100) in 411 RT-PCR negative individuals. The Standard Q Ag-RDT (SD Biosensor, Roche) was validated in 529 participants, with 170 positive Ag-RDT results out of 191 positive RT-PCR individuals, yielding a sensitivity of 89.0% (95%CI: 83.7–93.1). One false positive result was obtained in 338 RT-PCR negative individuals, yielding a specificity of 99.7% (95%CI: 98.4–100). For individuals presenting with fever 1–5 days post symptom onset, combined Ag-RDT sensitivity was above 95%. Lower sensitivity of 88.2% was seen on the same day of symptom development (day 0).ConclusionsWe provide an independent validation of two widely available commercial Ag-RDTs, both meeting WHO criteria of ≥80% sensitivity and ≥97% specificity. Although less sensitive than RT-PCR, these assays could be beneficial due to their rapid results, ease of use, and independence from existing laboratory structures. Testing criteria focusing on patients with typical symptoms in their early symptomatic period onset could further increase diagnostic value.

SARS-CoV-2 viral load dynamics and real-time RT-PCR cycle threshold interpretation in symptomatic non-hospitalised individuals in New Zealand: a multicentre cross sectional observational study

We conducted a multicentre cross sectional observational study of laboratory, public health and hospitalisation data for PCR-confirmed COVID-19 cases within the New Zealand Northern Region, between 12 February and 8 June 2020. The aim of this study was to describe population level SARS-CoV-2 upper respiratory tract (URT) viral load dynamics by stratifying positivity rates and polymerase chain reaction (PCR) cycle threshold (Ct) values of URT samples from COVID-19 cases by days since symptom onset, and to explore utility of Ct values in determining length of time post-infection and thus potential infectivity.Of 123,124 samples tested for SARS-CoV-2 by PCR, 579 samples (407 positive and 172 negative) from 368 symptomatic non-hospitalised individuals with PCR-confirmed infection were included. Sample positivity rate was 61.5% (8/13) for pre-symptomatic samples, rising to 93.2% (317/340) for samples collected during the purported symptomatic infectious period (days 0–10 post-symptom onset), and dropping to 36.3% (82/226) for post-infectious period samples (day 11 onwards). URT viral load peaked shortly after symptom onset, with median Ct values ranging 20.00–29.99 until 15 days post-symptom onset, and >30.00 after this time. Of samples with a Ct value of <20.00, 96.1% were collected during the symptomatic infectious period. However, of samples with a Ct value ≥30.00 and ≥35.00, 46.9% and 18.5%, respectively, were also collected during the symptomatic infectious period.The findings of this study indicate that at or soon after symptom onset represents the optimum time to test for SARS-CoV-2 in the URT, with median Ct values suggesting the useful testing window extends until around 15 days post-symptom onset. In asymptomatic individuals or those with unknown dates of symptom onset, Ct values <20.00 imply recent onset/potential infectivity, but Ct values ≥30.00 or ≥35.00 do not exclude recent onset/potential infectivity. Individual sample Ct values should not be used as an absolute marker of length of time post-infection or to exclude infectivity where date of symptom onset is unavailable.

Emerging and distinct video head impulse test responses in elderly with vestibular symptoms

IntroductionDizziness has been reported to be the most common symptom in elderly population. Video head impulse test, VHIT, allows clinicians to assess the vestibular function in elderly individuals, during their initial stages of vestibular symptoms. Inferences from VHIT responses were traditionally low vestibulo-ocular reflex gain or a normal vestibulo-ocular reflex gain. However, the possibility of a third and new variant of the vestibulo-ocular reflex gain has not been clinically explored yet. ObjectivesTo determine and report distinct patterns of vestibulo-ocular reflex gain using VHIT in elderly individuals with vestibular symptoms. MethodsRetrospective cross-sectional study was done on a group of elderly patients who were above 70 years of age. These individuals were subjected to VHIT during their symptomatic phase. A vestibulo-ocular reflex gain value between 0.80–01.20 (Horizontal plane) was considered normal. The gain above and below this cutoff range was considered abnormal. Results39 elderly patients (15 males and 24 females) whose mean age range was 74.71 years were evaluated for the VHIT response. Vestibulo-ocular reflex gain obtained was categorized into three distinct patterns: (i) normal vestibulo-ocular reflex gain, (ii) reduced vestibulo- ocular reflex gain and (iii) increased vestibulo-ocular reflex gain. The mean vestibulo- ocular reflex gain for both left and right horizontal canals varied significantly between the three groups (p < 0.05). No significant effect of age and vestibulo-ocular reflex gain was noted, though vestibulo-ocular reflex gain was higher in 80 years and above age (p > 0.05). ConclusionElderly individuals with dizziness may show varying responses with vestibulo-ocular reflex gain during the symptomatic period. The third type of hyperactive vestibule-ocular reflex responses that emerged from the current study were potential indicators of fluid dynamic changes in the inner ear. These responses need to be explored further as it relates to new clinical markers for both peripheral and central vestibular disorders.

The current therapeutical strategies in human brucellosis.

Prompt and adequate treatment of human brucellosis continues to be the most important strategy in its management, as eradication of animal brucellosis is not possible so far, and there is no adequate vaccine for humans. The goal of antibrucellar treatment is to alleviate and shorten the symptomatic period and reduce complications, relapses, and chronicity. Contemporary trends in the treatment of human brucellosis are postulated on the ability of Brucellae to persist in host macrophages through the inhibition of phagolysosome fusion and to survive for prolonged periods intracellularly without restricting basic cellular functions. As a result of this and despite satisfactory antibiotic treatment, relapses and therapeutical failures are inevitable to a certain degree. The current principles for the treatment of brucellosis advocate for a long enough treatment duration combined with antimicrobial regimens that possess activity in the intracellular acidic environment. In the future, other antimicrobial agents, immunomodulation, decrease in the intracellular acidic environment, or development of agents that would act on well-defined molecular bacterial targets, might be incorporated to improve the therapeutical effects.

Nowo wykryta arytmia komorowa u ozdrowieńca po chorobie koronawirusowej 2019

Cardiac complications are counted among the complications of coronavirus disease 2019 (COVID-19) in hospitalized patients. However, the data of non-hospitalized COVID-19 convalescents’ population is scant. This study presents a case of a 42-year-old woman with no medical history who underwent SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus 2) infection at 16 March 2020. She had a fever (38 degrees Celsius) and dyspnoea that resolved after chloroquine administration so the patient was not hospitalized. One week later she reported palpitations and fatigue of functional class II New York Heart Association despite negative repeated polymerase chain reaction results (23 rd March, 1 st April). Within 6 weeks she was referred to a cardiologist. The laboratory test results revealed slightly increased high-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide. On electrocardiogram (ECG), single ventricular extrasystoles of right bundle branch block shape were observed. 24-hrs ECG Holter monitoring revealed additionally symptomatic periods of bigeminy and 4.2 thousands of ventricular extrasystoles. The cardiac magnetic resonance showed typical post-inflammatory myocardial changes with no active inflammation. No pharmacotherapy was applied. The symptoms have ceased. In the 4th month, 24-hrs ECG Holter revealed the recovery from arrhythmia. The presented case showed that long-term medical observation is worth to be considered even for non-hospitalized patients with a mild course of SARS-CoV-2 infection.

The outcome of 41 Late-Diagnosed Turkish GA-1 Patients: A Candidate for the Turkish NBS

Glutaric aciduria type 1(GA-1) is an inherited cerebral organic aciduria. Untreated patients with GA-1 have a risk of acute encephalopathic crises during the first 6 years of life. In so far as GA-1 desperately does not exist in Turkish newborn screening (NBS) program, most patients in our study were late-diagnosed. This study included 41 patients diagnosed with acylcarnitine profile, urinary organic acids, mutation analyses in the symptomatic period. We presented with clinical, neuroradiological, and molecular data of our 41 patients. The mean age at diagnosis was 14.8 ± 13.9 (15 days to 72 months) and, high blood glutaconic acid, glutarylcarnitine and urinary glutaric acid (GA) levels in 41 patients were revealed. Seventeen different mutations in the glutaryl-CoA dehydrogenase gene were identified, five of which were novel. The patients, most of whom were late-diagnosed, had a poor neurological outcome. Treatment strategies made a little improvement in dystonia and the frequency of encephalopathic attacks. All GA-1 patients in our study were severely affected since they were late-diagnosed, while others show that GA-1 is a treatable metabolic disorder if it is diagnosed with NBS. This study provides an essential perspective of the severe impact on GA-1 patients unless it is diagnosed with NBS. We immediately advocate GA-1 to be included in the Turkish NBS.

Reconstructing the household transmission of influenza in the suburbs of Tokyo based on clinical cases

BackgroundInfluenza is a public health issue that needs to be addressed strategically. The assessment of detailed infectious profiles is an important part of this effort. Household transmission data play a key role in estimating such profiles. We used diagnostic and questionnaire-based data on influenza patients at a Japanese clinic to estimate the detailed infectious period (as well as incubation period, symptomatic and infectious periods, and extended infectious period after recovery) and the secondary attack ratio (SAR) of influenza for households of various sizes based on a modified Cauchemez-type model.ResultsThe data were from enrolled patients with confirmed influenza who were treated at the Hirotsu Clinic (Kawasaki, Japan) with a neuraminidase inhibitor (NAI) during six northern hemisphere influenza seasons between 2010 and 2016. A total of 2342 outpatients, representing 1807 households, were included. For influenza type A, the average incubation period was 1.43 days (95% probability interval, 0.03–5.32 days). The estimated average symptomatic and infective period was 1.76 days (0.33–4.62 days); the extended infective period after recovery was 0.25 days. The estimated SAR rose from 20 to 32% as household size increased from 3 to 5. For influenza type B, the average incubation period, average symptomatic and infective period, and extended infective period were estimated as 1.66 days (0.21–4.61), 2.62 days (0.54–5.75) and 1.00 days, respectively. The SAR increased from 12 to 21% as household size increased from 3 to 5.ConclusionAll estimated periods of influenza type B were longer than the corresponding periods for type A. However, the SAR for type B was less than that for type A. These results may reflect Japanese demographics and treatment policy. Understanding the infectious profiles of influenza is necessary for assessing public health measures.

SARS-CoV-2 infection prevalence and characteristics in domestic contacts: Study of 39 families and 132 people in a general medicine clinic in Toledo (Spain). implications for the general practitioner

BackgroundMost people with COVID-19 receive care at home, increasing the likelihood of exposure for household members.ObjectiveTo study the prevalence and characteristics of secondary cases in families after the appearance of a primary caseMethodologyAn observational and retrospective study of families with at least one polymerase chain reaction (PCR) confirmed COVID-19 primary case was conducted from March 15 to December 25, 2020, in a general medicine office in Toledo, Spain. Socio-demographic and clinical variables were compared between primary and secondary cases in the families. The outcome of interest was secondary attack rate of SARS-CoV-2 within the family.Results39 families with a primary case (average size 3.4 members) with a total of 132 cohabitants were included. There were 22 cohabitants with negative PCR (22/92 = 24%), 70 secondary cases with positive PCR (Secondary attack rate 76%), of which 25 were asymptomatic (25/70 = 36%), and a cohabiting new-born. A high frequency of people from ethnic minorities, low household income and complex families was found, both in primary and secondary cases. The secondary cases with respect to the primary ones were more women, younger, students and with a lower socio-occupational level, with more asymptomatic cases, and milder symptomatic cases.ConclusionsIn this context, the prevalence of secondary domestic contacts is very high, and it occur in young women, being asymptomatic or mild. The high secondary attack rate suggests the importance of the pre-symptomatic or early symptomatic period of COVID-19, as well as the possible failure to comply with isolation measures.

Symptom Provocation During Aerobic and Dynamic Supervised Exercise Challenges in Adolescents With Sport-Related Concussion.

Supervised exercise challenges (SECs) have been shown to be safe and beneficial in the early symptomatic period after concussion. Thus far, most in-clinic SECs studied have included a form of basic aerobic exercise only. An SEC that also includes dynamic forms of exercise mimics all steps of a standard return-to-play progression and may enhance the detection of concussion symptoms to guide in-clinic management decisions. To determine whether an SEC that includes a dynamic SEC (DSEC) uncovered symptoms that would not have been identified by an SEC involving an aerobic SEC (ASEC) alone in adolescent patients with sport-related concussion. Retrospective case series. Multidisciplinary sport concussion clinic at a tertiary care center. A total of 65 adolescent athletes (mean age = 14.9 ± 2.0 years, 72.3% males) who underwent an in-clinic SEC within 30 days of concussion. Presence of pre-exercise symptoms and symptom provocation during the SEC were recorded, with exercise-provoked symptoms categorized as occurring during ASEC or DSEC. Of the total patient sample, 69.2% (n = 45/65) experienced symptom provocation at some point during the SEC. Symptoms were provoked in 20 patients during the ASEC, whereas 25 completed the ASEC without symptom provocation before becoming symptomatic during the subsequent DSEC and 20 completed the SEC without any symptom provocation. Of the 65 patients in the total sample, 46 were asymptomatic immediately before the SEC. Of these previously asymptomatic patients, 23.9% (n = 11/46) experienced symptom provocation during the ASEC, and an additional 37.0% (n = 17/46) remained asymptomatic during the ASEC but then developed symptoms during the DSEC. The ASEC alone may not detect symptom provocation in a significant proportion of concussion patients who otherwise would develop symptoms during a DSEC.

Advance on the infectivity of SARS-CoV-2 infection at different stages

The studies on infectiousness of person infected with SARS-CoV-2 at different stages of illness are an important basis for making effective prevention and control measures such as investigating the infectious source, determining the scope of close contacts and the timing of case isolation. This review discusses the infectiousness of cases infected with SARS-CoV-2 in the incubation period, symptomatic period and convalescent period by reviewing national and international literatures, technical and professional guidelines. Existing researches suggest that the infectious viruses could be isolated at the end of the incubation period as well as since illness onset, and viral load in upper respiratory tract swabs reached the peak on day 4-6 after illness onset and thereafter began to decline, implying the infectiousness was relatively strong at the end of incubation period and within one week after illness onset. Although there were a few cases who tested positive for SARS-CoV-2 after recovery, no evidence was found to indicate these cases can cause the transmission.

Stepwise approach in the management of oral lichen planus

Lichen planus is a chronic inflammatory disease in the skin, hair, nails, and mucous membranes. Like in other sites, oral lichen planus (OLP) includes asymptomatic and flare-up or symptomatic periods. The symptomatic period is characterized by erosive, ulcerative, or painful symptoms. In addition, some lesions may have potentially malignant transformation. Despite many molecular-based studies, the OLP etiology is still unclear. Hence, there is no gold-standard therapy for OLP so far. The management of symptomatic lesions is based on each individual’s clinical features, and treatment outcomes are often unpredictable. That explains why most dentists are not confident in dealing with this disease. Nevertheless, there is a consensus among the majority of authors that the pathogenesis of OLP, as an immune-mediated disease, is related to T-lymphocyte immunological dysfunction. Medical treatment, using immunosuppressant therapies or immunomodulators, aims (1) to alleviate painful symptoms, (2) to heal the ulcerative and atrophic lesions, (3) to reduce the risk of malignant transformation, and (4) to prolong the symptom‑free intervals. This review article aims to synthesize current literature evidence and integrate the authors’ experience in suggesting a stepwise approach to manage OLP patients.

Pervasive inflammatory activation in patients with deficiency in very-long-chain acyl-coA dehydrogenase (VLCADD).

ObjectivesVery‐long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is a disorder of fatty acid oxidation. Symptoms are managed by dietary supplementation with medium‐chain fatty acids that bypass the metabolic block. However, patients remain vulnerable to hospitalisations because of rhabdomyolysis, suggesting pathologic processes other than energy deficit. Since rhabdomyolysis is a self‐destructive process that can signal inflammatory/immune cascades, we tested the hypothesis that inflammation is a physiologic dimension of VLCADD.MethodsAll subjects (n = 18) underwent informed consent/assent. Plasma cytokine and cytometry analyses were performed. A prospective case analysis was carried out on a patient with recurrent hospitalisation. Health data were extracted from patient medical records.ResultsPatients showed systemic upregulation of nine inflammatory mediators during symptomatic and asymptomatic periods. There was also overall abundance of immune cells with high intracellular expression of IFNγ, IL‐6, MIP‐1β (CCL4) and TNFα, and the transcription factors p65‐NFκB and STAT1 linked to inflammatory pathways. A case analysis of a patient exhibited already elevated plasma cytokine levels during diagnosis in early infancy, evolving into sustained high systemic levels during recurrent rhabdomyolysis‐related hospitalisations. There were corresponding activated leukocytes, with higher intracellular stores of inflammatory molecules in monocytes compared to T cells. Exposure of monocytes to long‐chain free fatty acids recapitulated the cytokine signature of patients.ConclusionPervasive plasma cytokine upregulation and pre‐activated immune cells indicate chronic inflammatory state in VLCADD. Thus, there is rationale for practical implementation of clinical assessment of inflammation and/or translational testing, or adoption, of anti‐inflammatory intervention(s) for personalised disease management.

Surgical Treatment of Femoroacetabular Impingement: Minimum 10-Year Outcome and Risk Factors for Failure.

Background:Femoroacetabular impingement (FAI) is a well-known cause of hip pain and dysfunction in young adults. Surgical treatment has been widely popularized during the past decade. However, most reported results have been limited to short-term and intermediate-term follow-up. The long-term success rate and risk factors for failure are largely unknown. This study aimed to report the long-term (minimum, 10 years) clinical outcomes of surgical treatment of FAI and to describe the clinical and radiographic parameters associated with the failure of treatment involving femoroacetabular osteoplasty (FAO) and labral repair.Methods:Using our prospective hip preservation database, 164 patients (178 hips) who had undergone FAO between January 2005 and April 2009 were identified. Patient demographic characteristics, clinical history, duration of preoperative symptoms, radiographic parameters (preoperative and postoperative alpha angles, hip dysplasia and retroversion, Tönnis grade for osteoarthritis), and intraoperative findings were reviewed and compared between the success and failure groups. At a minimum 10-year follow-up, clinical functional outcomes (modified Harris hip score [mHHS] and Short Form-36 [SF-36] at 6 weeks, 6 months, 1 year, and 10 years) and failure rates (conversion to total hip arthroplasty [THA]) were collected.Results:The mean patient age (and standard deviation) was 34.3 ± 8.4 years, and 65 patients (40%) were female. After the surgical procedure, there was significant improvement in the mean mHHS (59.3 ± 7.3 points preoperatively to 88.4 ± 7.3 points postoperatively) and the mean SF-36 (61.3 ± 8.4 points preoperatively to 89.1 ± 7.2 points postoperatively). At a mean follow-up of 12.5 years, 12% (22 hips) required conversion to THA, with a mean time to THA of 5.3 ± 2.0 years. Older age, longer preoperative symptomatic period, higher preoperative and postoperative alpha angles, presence of hip dysplasia, a higher Tönnis grade, joint space narrowing, and a full-thickness acetabular chondral lesion at the time of the FAO were identified as risk factors for failure and conversion to THA.Conclusions:Patients with symptomatic FAI who undergo a surgical procedure experience pain relief and functional improvement that appear to endure over a decade in the majority of patients. This study on a relatively large cohort with a long-term follow-up has also identified patients who are at a higher risk for treatment failure.Level of Evidence:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.