Longitudinal Analysis of Antibody Responses to the mRNA BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis: A 6-Month Follow-Up

Background: Patients on hemodialysis (HD) are at higher risk for COVID-19, overall are poor responders to vaccines, and were prioritized in the Portuguese vaccination campaign.Objective: This work aimed at evaluating in HD patients the immunogenicity of BTN162b2 after the two doses induction phase, the persistence of specific antibodies along time, and factors predicting these outcomes.Methods: We performed a prospective, 6-month long longitudinal cohort analysis of 156 HD patients scheduled to receive BTN162b2. ELISA quantified anti-spike IgG, IgM, and IgA levels in sera were collected every 3 weeks during the induction phase (t0 before vaccine; t1, d21 post first dose; and t2 d21 post second dose), and every 3–4 months during the waning phase (t3, d140, and t4, d180 post first dose). The age-matched control cohort was similarly analyzed from t0 to t2.Results: Upon exclusion of participants identified as previously exposed to SARS-CoV-2, seroconversion at t1 was lower in patients than controls (29 and 50%, respectively, p = 0.0014), while the second vaccine dose served as a boost in both cohorts (91 and 95% positivity, respectively, at t2, p = 0.2463). Lower response in patients than controls at t1 was a singularity of the participants ≤ 70 years (p = 2.01 × 10−05), associated with immunosuppressive therapies (p = 0.013), but not with lack of responsiveness to hepatitis B. Anti-spike IgG, IgM, and IgA levels decreased at t3, with IgG levels further waning at t4 and resulting in >30% seronegativity. Anti-spike IgG levels at t1 and t4 were correlated (ρ = 0.65, p < 2.2 × 10−16).Conclusions: While most HD patients seroconvert upon 2 doses of BNT162b2 vaccination, anti-spike antibodies levels wane over the following 4 months, leading to early seroreversion in a sizeable fraction of the patients. These findings warrant close monitoring of COVID-19 infection in vaccinated HD patients, and advocate for further studies following reinforced vaccination schedules.

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Longitudinal analysis of antibody responses to the Pfizer BNT162b2 vaccine in Patients Undergoing Maintenance Hemodialysis

10.1101/2021.07.20.21260849 ◽

2021 ◽

Author(s):

André Weigert ◽

Marie-Louise Bergman ◽

Ligia Gonçalves ◽

Iolanda Godinho ◽

Nádia Duarte ◽

...

Keyword(s):

Vaccination Campaign ◽

Cohort Analysis ◽

Vaccine Dose ◽

Antibody Responses ◽

Hepatitis B Vaccination ◽

Maintenance Hemodialysis ◽

Host Protection ◽

Vaccine Schedule ◽

Sizable Proportion ◽

Prospective Longitudinal

Background and objectives: Patients undergoing hemodialysis are at higher risk of developing severe complications upon SARS-CoV-2 infection and were prioritized in the Portuguese vaccination campaign. Immunogenicity of COVID-19 vaccines in hemodialyzed patients was not addressed by the phase 3 clinical trials leading to their emergency approval. Design, setting, participants, and measurements: We performed a prospective, longitudinal, cohort analysis of 156 hemodialyzed patients and 143 age-matched controls scheduled for BTN162b2 vaccine. Excluded from analysis were five patients previously diagnosed with SARS-CoV-2, three sero-positive for anti-SARS-CoV-2 N, two dropouts and two deaths. ELISA was used to quantify anti-full-length Spike IgG, IgM and IgA levels in sera collected at day of the first vaccine dose (t0); 3 weeks later (day of the second dose, t1); and 3 weeks after the second inoculation (t2). Results: Seroconversion after the first vaccine dose (t1) was remarkably low in patients, with positivity for anti-spike IgG, IgM and IgA antibodies of 29.4%, 12% and 41%, respectively. The second vaccine dose raised seroconversion to 90.9% and 83.9% for IgG and IgA, respectively, while IgM positivity remained unchanged. At t1 the anti-Spike IgG level was significantly lower in patients with ages below 70 years when compared to age-matched controls, showing a profile similar to aged individuals (above 70 years). Immunosuppression was associated with lower antibody responses along the vaccine schedule (p=0.005 at t1; p=0.008 at t2). Noteworthy, previous unresponsiveness to hepatitis B vaccination (75/129, 58% of patients negative for anti-HBs antibodies) did not correlate with humoral unresponsiveness to BTN162b2. Other clinical and laboratory parameters had marginal correlations with response to vaccination. Conclusions: The large majority of hemodialyzed patients showed IgG seroconversion upon BNT162b2 mRNA vaccination but a sizable proportion of patients presented poor responses. These results support further investigation into the relationship between vaccination, serologic response and host protection.

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Delayed systemic urticarial reactions following mRNA COVID-19 vaccination

Allergy and Asthma Proceedings ◽

10.2500/aap.2022.43.210101 ◽

2022 ◽

Vol 43 (1) ◽

pp. 40-43 ◽

Cited By ~ 1

Author(s):

Mitchell M. Pitlick ◽

Avni Y. Joshi ◽

Alexei Gonzalez-Estrada ◽

Sergio E. Chiarella

Keyword(s):

Messenger Rna ◽

Skin Testing ◽

Vaccination Campaign ◽

Case Series ◽

Vaccine Dose ◽

Retrospective Case ◽

Life Threatening ◽

History Of ◽

The Mean ◽

To Receive

Background: As the vaccination campaign in response to the coronavirus disease 2019 (COVID-19) pandemic continues, concerns with regard to adverse reactions to the vaccine remain. Although immediate hypersensitivity reactions have received much attention, delayed systemic urticarial reactions after vaccination can occur. Objective: To describe the clinical presentation, vaccine excipient skin testing results, and outcomes of subsequent COVID-19 vaccination in patients who experienced delayed systemic urticarial reactions after messenger RNA (mRNA) COVID-19 vaccination. Methods: This was a retrospective case series of 12 patients referred to the Mayo Clinics in Rochester, Minnesota, and Jacksonville, Florida, between January 19, 2021, and April 30, 2021, for evaluation of delayed systemic urticarial reactions after mRNA COVID-19 vaccination. Demographics, medical and allergic history, reaction details, vaccine excipient skin testing results (when performed), and the outcome after subsequent vaccination were collected for each patient. Results: The mean age of the patients was 52 years, all were white, and 9 (75%) were women. Half of the patients had a history of drug allergy, and one had a history of chronic spontaneous urticaria. Seven patients reacted to the Pfizer-BioNTech vaccine and five reacted to the Moderna vaccine. Seven patients developed symptoms between 8 and 24 hours after vaccination. Nine patients required antihistamines for treatment. The median time to symptom resolution was 4 days. Nine patients underwent allergist-directed COVID-19 vaccine excipient skin testing, all of which were negative. Ten patients chose to receive their next mRNA COVID-19 vaccine dose, and four patients experienced recurrent delayed urticaria. Conclusion: Delayed systemic urticarial reactions after mRNA COVID-19 vaccination were not life-threatening, could be treated with antihistamines, and were not predicted with vaccine excipient skin testing. They were not a contraindication to subsequent vaccination, although patients should be counseled with regard to the possibility of recurrence.

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Long Term Follow-Up of the Gimema GSI 103 AMLE Randomized Trial: Daunoxome Seems To Improve Disease-Free Survival (DFS) of Elderly Patients with Acute Myelogenous Leukemia (AML).

Blood ◽

10.1182/blood.v108.11.1979.1979 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1979-1979 ◽

Cited By ~ 1

Author(s):

Roberto Latagliata ◽

Massimo Breccia ◽

Simona Iacobelli ◽

Paola Fazi ◽

Giovanni Martinelli ◽

...

Keyword(s):

Elderly Patients ◽

Univariate Analysis ◽

Myelogenous Leukemia ◽

Phase Iii ◽

Induction Treatment ◽

Induction Phase ◽

Long Term Follow Up ◽

To Receive

Abstract The GSI 103 AMLE was a randomized phase III clinical trial to explore the efficacy of DaunoXome (DNX) versus Daunorubicin (DNR) standard treatment in AML elderly patients. From 10/2001 to 2/2004, 301 patients aged 61 to 75 years with a diagnosis of AML according to WHO classification and eligible for intensive chemotherapy were enrolled in this trial by 39 GIMEMA Centers. Patients were randomized to receive induction treatment with DNR (45 mg/sqm day 1 to 3) or DNX (80 mg/sqm day 1 to 3) plus AraC (100 mg/sqm day 1 to 7 by continuous infusion): as consolidation therapy, patients in CR received a further course of the assigned induction treatment. After the consolidation course, patients in CR underwent a 2nd randomization independently from the 1st random, to receive as maintenance therapy either AraC (20 mg twice daily day 1 to 10) plus all-trans retinoic acid (ATRA) (45 mg/sqm day 1 to 10) every 28 days for a maximum of 12 cycles (Arm A) or no further treatment (Arm B). 153 patients were enrolled in the DNR arm and 148 in the DNX arm: the two arms were comparable as to relevant patient characteristics, including karyotype. In the DNR arm, 77 patients (50.3%) achieved CR, 56 (36.6%) were resistant and 20 (13.1%) died during induction (ID). In the DNX arm, 73 patients (49.3%) achieved CR, 47 (31.8%) were resistant and 28 (18.9%) died during induction. Differences between the two arms at univariate analysis were not statistically significant either considering the 3 different types of response or considering ID versus other (Chi-square 0.34 and 0.17 respectively). After CR, the effect of DNX seems to be time-related, due to higher incidence of early deaths in CR (11% vs 3%, p=0.053) and lower incidence of relapse beyond 6 months (at 24 months 60% vs 80%, p=0.064). This translates in a cross of the OS and DFS curves between the two arms, with initial advantage for the DNR arm followed by an advantage for DNX arm after 12 months from diagnosis. A time-dependent covariate Cox model and a landmark analysis on patients in CR after 6 months revealed a better outcome of DNX patients (p= 0.029 and p=0.092, respectively) in the long term DFS follow-up. No difference has been observed in the DFS curves according to maintenance randomization. In conclusion, DNX is as effective as DNR in the induction phase of AML elderly patients, with a trend of increased early toxicity (ID + deaths in CR): however, DNX seems to improve the OS and DFS in the long-term follow-up of these patients, due to a reduction of late relapses. Further trials in more selected elderly patients or in younger patients will be helpful to define the exact role of DNX in AML.

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Third COVID-19 Vaccine Dose Boosts Neutralising Antibodies in Poor Responders

10.1101/2021.11.30.21266716 ◽

2021 ◽

Author(s):

Douglas F. Lake ◽

Alexa J. Roeder ◽

Maria J. Gonzalez-Moa ◽

Megan Koehler ◽

Erin Kaleta ◽

...

Keyword(s):

Vaccine Dose ◽

Fold Increase ◽

Poor Responders ◽

Healthy Individuals ◽

Neutralising Antibodies ◽

Medical Institutions ◽

Vaccine Manufacturer ◽

Clinical Protection ◽

Study Participants

ABSTRACTObjectiveTo determine if poor responders to COVID-19 RNA vaccines (<50% neutralisation) after two doses would remain poor responders, or if a third dose could elicit high levels of NAbs.DesignClinical follow-up studySettingAcademic and medical institutions in USAParticipants269 healthy individuals ranging in age from 19 to 80 (Average age = 51; 165 females and 104 males) who received either BNT162b2 (Pfizer) or mRNA1273 (Moderna) vaccines.Main Outcome MeasuresNAb levels were measured: i) 2-4 weeks after a second vaccine dose, ii) 2-4 months after the second dose, iii) within 1-2 weeks prior to a third dose and iv) 2-4 weeks after a third RNA vaccine dose.ResultsIn 269 study participants, percent neutralisation ranged from 0% to 99% 2-4 weeks after a second vaccine dose. The majority of vaccine recipients (154/269, 57%) demonstrated NAb levels at ≥75% 2-4 weeks after their second dose. Our study also revealed that 25% of vaccine recipients did not neutralise above 50% (Median neutralisation = 21%, titers <1:80) within a month after their second dose. We called these individuals “vaccine poor responders” (VPRs). Twenty-three VPRs ranging in age from 31 to 79 (10 males, 13 females, average age = 62.5) independently obtained a third dose of either BNT162b2 or mRNA-1273 vaccine 1-8 months (average = 5 months) after their second dose. Within a month after their third dose, poor responders showed an average 20-fold increase in NAb levels (range 46%-99%).ConclusionsThe results suggest that poor responders are not permanently poor responders; they can generate high NAb levels with an additional vaccine dose–independent of mRNA vaccine manufacturer. Previous reports indicate that NAb levels decline much more rapidly than clinical protection from hospitalisation and disease, but that does not account for vaccine recipients who never generated high levels of NAbs after two doses. It is possible that poor responders are a source of breakthrough infections. Although it is not known what levels of NAbs protect from infection or disease, many vaccine recipients in high-risk professions may wish to keep peripheral NAb levels high, limiting infection, asymptomatic viral replication, and potential transmission.

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A Pilot Study of Mobile Telephone Message Interventions with Suicide Attempters in China

Crisis ◽

10.1027/0227-5910/a000017 ◽

2010 ◽

Vol 31 (2) ◽

pp. 109-112 ◽

Cited By ~ 35

Author(s):

Hui Chen ◽

Brian L. Mishara ◽

Xiao Xian Liu

Keyword(s):

Pilot Study ◽

Effective Means ◽

Text Message ◽

Text Messages ◽

Mobile Telephone ◽

Future Research ◽

Quick Method ◽

Suicide Attempters ◽

To Receive

Background: In China, where follow-up with hospitalized attempters is generally lacking, there is a great need for inexpensive and effective means of maintaining contact and decreasing recidivism. Aims: Our objective was to test whether mobile telephone message contacts after discharge would be feasible and acceptable to suicide attempters in China. Methods: Fifteen participants were recruited from suicide attempters seen in the Emergency Department in Wuhan, China, to participate in a pilot study to receive mobile telephone messages after discharge. All participants have access to a mobile telephone, and there is no charge for the user to receive text messages. Results: Most participants (12) considered the text message contacts an acceptable and useful form of help and would like to continue to receive them for a longer period of time. Conclusions: This suggests that, as a low-cost and quick method of intervention in areas where more intensive follow-up is not practical or available, telephone messages contacts are accessible, feasible, and acceptable to suicide attempters. We hope that this will inspire future research on regular and long-term message interventions to prevent recidivism in suicide attempters.

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Lesson Study dan Implikasinya Terhadap Pembelajaran Berbasis Kurikulum Tingkat Satuan Pendidikan

International Conference of Moslem Society ◽

10.24090/icms.2016.2420 ◽

2016 ◽

Vol 1 ◽

pp. 189-196

Author(s):

Vian Harsution

Keyword(s):

Learning Environment ◽

Learning Process ◽

Lesson Study ◽

Learning Difficulties ◽

Learning Needs ◽

Democratic Leadership ◽

Entrepreneurial Spirit ◽

To Receive

Lesson study is a systematic, collaborative, and sustainable method of improving the quality of learning. Lesson study emphasizes the exploration of students’ learning needs; teacher openness towards learning difficulties encountered; the willingness of teachers to receive and provide advice and solutions to the difficulties encountered; and the consistency of the various parties to follow up the suggestions and solutions. Implementation of lesson study involving teachers, principals, and experts in the field of education. Kurikulum tingkat satuan pendidikan or abbreviated KTSP is operational curriculum formulated and implemented by each educational unit. KTSP has the characteristics, namely: giving broad autonomy to the educational unit, involving the community and parent participation, involving the democratic leadership of the principal, and require the support of a working team that is synergistic and transparent. KTSP based on the learning process, needs to be supported by a conducive learning environment and fun to be created by teachers.Teachers and principals in a professional, systematic and collaborative create an atmosphere that fosters independence, tenacity, entrepreneurial spirit, adaptive and proactive nature of the learning process. Thus, the learning needs of students who fulfilled optimally and professional ability of teacher who have increased on an ongoing basis, may usher in success – based learning KTSP. It means that the lesson study provides positive implications for the KTSP – based learning.

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Gamma Knife surgery for low-flow cavernous sinus dural arteriovenous fistulas

Journal of Neurosurgery ◽

10.3171/2010.8.gks10977 ◽

2010 ◽

Vol 113 (Special_Supplement) ◽

pp. 21-27 ◽

Cited By ~ 5

Author(s):

Hyun Ho Jung ◽

Jong Hee Chang ◽

Kum Whang ◽

Jin Soo Pyen ◽

Jin Woo Chang ◽

...

Keyword(s):

Gamma Knife ◽

Cavernous Sinus ◽

Transarterial Embolization ◽

Gamma Knife Surgery ◽

Low Flow ◽

Close Monitoring ◽

Arteriovenous Fistulas ◽

Ocular Symptoms ◽

Dural Arteriovenous Fistulas

Object The purpose of this study was to assess the efficacy of Gamma Knife surgery (GKS) for treating cavernous sinus dural arteriovenous fistulas (CSDAVFs). Methods Of the 4123 GKSs performed between May 1992 and March 2009, 890 procedures were undertaken to treat vascular lesions. In 24 cases, the vascular lesion that was treated was a dural arteriovenous fistula, and in 6 of these cases, the lesion involved the cavernous sinus. One of these 6 cases was lost to follow-up, leaving the other 5 cases (4 women and 1 man) to comprise the subjects of this study. All 5 patients had more than 1 ocular symptom, such as ptosis, chemosis, proptosis, and extraocular movement palsy. In all patients, CSDAVF was confirmed by conventional angiography. Three patients were treated by GKS alone and 2 patients were treated by GKS combined with transarterial embolization. The median follow-up period after GKS in these 5 cases was 30 months (range 9–59 months). Results All patients experienced clinical improvement, and their improvement in ocular symptoms was noticed at a mean of 17.6 weeks after GKS (range 4–24 weeks). Two patients received embolization prior to GKS but did not display improvement in ocular symptoms. An average of 20 weeks (range 12–24 weeks) was needed for complete improvement in clinical symptoms. There were no treatment-related complications during the follow-up period. Conclusions Gamma Knife surgery should be considered as a primary, combined, or additional treatment option for CSDAVF in selected cases, such as when the lesion is a low-flow shunt without cortical venous drainage. For those selected cases, GKS alone may suffice as the primary treatment method when combined with close monitoring of ocular symptoms and intraocular pressure.

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The Effect of the Familiarity of a Survey Sender on Response Outcomes in a Large-Scale Survey of Emergency Medical Services Agencies

Evaluation & the Health Professions ◽

10.1177/01632787211030635 ◽

2021 ◽

Vol 44 (3) ◽

pp. 260-267

Author(s):

Morgan M. Millar ◽

Hilary A. Hewes ◽

Andrea L. Genovesi ◽

Michael Ely ◽

Braden Green ◽

...

Keyword(s):

Emergency Medical Services ◽

Large Scale ◽

Nationwide Survey ◽

Survey Response ◽

Medical Services ◽

Healthcare Organizations ◽

Emergency Medical ◽

Established Relationship ◽

To Receive

Survey response is higher when the request comes from a familiar entity compared to an unknown sender. Little is known about how sender influences response to surveys of organizations. We assessed whether familiarity of the sender influences response outcomes in a survey of emergency medical services agencies. Emergency medical services agencies in one U.S. state were randomly assigned to receive survey emails from either a familiar or unfamiliar sender. Both deployment approaches were subsequently used nationwide, with each state selecting one of the two contact methods. Experimental results showed that requests from the familiar sender achieved higher survey response (54.3%) compared to requests from the unfamiliar sender (36.9%; OR: 2.03; 95% CI: 1.23, 3.33). Similar results were observed in the subsequent nationwide survey; in states where the familiar sender deployed the survey, 62.0% of agencies responded, compared to 51.0% when the survey was sent by the unfamiliar sender (OR: 1.57; 95% CI: 1.47, 1.67). The response difference resulted in nearly 60 additional hours of staff time needed to perform telephone follow-up to nonrespondents. When surveying healthcare organizations, surveyors should recognize that it is more challenging to obtain responses without a pre-established relationship with the organizations.

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Neurological Evaluation of Patients with Newly Diagnosed Coeliac Disease Presenting to Gastroenterologists: A 7-Year Follow-Up Study

Nutrients ◽

10.3390/nu13061846 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1846

Author(s):

Marios Hadjivassiliou ◽

Iain D. Croall ◽

Richard A. Grünewald ◽

Nick Trott ◽

David S. Sanders ◽

...

Keyword(s):

Coeliac Disease ◽

Brain Imaging ◽

Cerebellar Atrophy ◽

Neurological Dysfunction ◽

Close Monitoring ◽

Newly Diagnosed ◽

Positive Serology ◽

Original Cohort ◽

Follow Up Study

We have previously shown that 67% of patients with newly diagnosed coeliac disease (CD) presenting to gastroenterologists have evidence of neurological dysfunction. This manifested with headache and loss of co-ordination. Furthermore 60% of these patients had abnormal brain imaging. In this follow-up study, we re-examined and re-scanned 30 patients from the original cohort of 100, seven years later. There was significant reduction in the prevalence of headaches (47% to 20%) but an increase in the prevalence of incoordination (27% to 47%). Although those patients with coordination problems at baseline reported improvement on the gluten free diet (GFD), there were 7 patients reporting incoordination not present at baseline. All 7 patients had positive serology for one or more gluten-sensitivity related antibodies at follow-up. In total, 50% of the whole follow-up cohort were positive for one or more gluten-related antibodies. A comparison between the baseline and follow-up brain imaging showed a greater rate of cerebellar grey matter atrophy in the antibody positive group compared to the antibody negative group. Patients with CD who do not adhere to a strict GFD and are serological positive are at risk of developing ataxia, and have a significantly higher rate of cerebellar atrophy when compared to patients with negative serology. This highlights the importance of regular review and close monitoring.

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Radiofrequency ablation for markedly incompetent perforators versus compression therapy in the management of post-phelebtic venous ulcers: A randomized controlled trial

Vascular ◽

10.1177/17085381211010022 ◽

2021 ◽

pp. 170853812110100

Author(s):

Mohamed Shukri Abdelgawad ◽

Amr M El-Shafei ◽

Hesham A Sharaf El-Din ◽

Ehab M Saad ◽

Tamer A Khafagy ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Radiofrequency Ablation ◽

Controlled Trial ◽

Compression Therapy ◽

Randomized Controlled ◽

Venous Ulcers ◽

Group A ◽

Group B ◽

To Receive

Background Venus ulcers developed mainly due to reflux of incompetent venous valves in perforating veins. Patients and methods In this randomized controlled trial, 119 patients recruited over two years, with post-phelebtic venous leg ulcers, were randomly assigned into one of two groups: either to receive radiofrequency ablation of markedly incompetent perforators (Group A, n = 62 patients) or to receive conventional compression therapy (Group B, n = 57 patients). Follow-up duration required for ulcer healing continued for 24 months post randomization. Results Statistically significant shorter time to healing (ulcer complete healing or satisfactory clinical improvement) between both groups (56 patients, 90.3% of cases in Group A versus 44 patients 77.2% of cases in Group B) over the follow-up period of 24 months was attained ( p = 0.001). Also, significantly different ulcer recurrence was recorded between both groups, 8 patients (12.9%) in Group A versus 19 patients (33.3%) in Group B ( p = 0.004). Conclusion In absence of deep venous obstruction, the monopolar radiofrequency ablation for incompetent perforators is a feasible and effective method that surpasses the traditional compression protocol for incompetent perforator-induced venous ulcers in terms of time required for healing even in the presence of unresolved deep venous valvular reflux.

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