Immunogenicity and safety of RAZI recombinant spike protein vaccine (RCP) as a booster dose after priming with BBIBP-CorV: a parallel two groups, randomized, double blind trial.

BACKGROUND: The immunity induced by primary vaccination is effective against COVID-19; however, booster vaccines are needed to maintain vaccine-induced immunity and improve protection against emerging variants. Heterologous boosting is believed to result in more robust immune responses. This study investigated the safety and immunogenicity of the Razi Cov Pars vaccine (RCP) as a heterologous booster dose in people primed with Beijing Bio-Institute of Biological Products Coronavirus Vaccine (BBIBP-CorV). METHODS: We conducted a randomized, double-blind, active-controlled trial in adults aged 18 and over primarily vaccinated with BBIBP-CorV, an inactivated SARS-CoV-2 vaccine. Eligible participants were randomly assigned (1:1) to receive a booster dose of RCP or BBIBP-CorV vaccines. The primary outcome was neutralizing antibody activity measured by a conventional virus neutralization test (cVNT). The secondary efficacy outcomes included specific IgG antibodies against SARS-CoV-2 spike (S1 and receptor-binding domain, RBD) antigens and cell-mediated immunity. We measured humoral antibody responses at 2 weeks (in all participants) and 3 and 6 months (a subgroup of 101 participants) after the booster dose injection. The secondary safety outcomes were solicited and unsolicited immediate, local, and systemic adverse reactions. RESULTS: We recruited 483 eligible participants between December 7, 2021, and January 13, 2022. The mean age was 51.9 years, and 68.1% were men. Neutralizing antibody titers increased about 3 (geometric mean fold increase, GMFI = 2.77, 95% CI 2.26-3.39) and 21 (GMFI = 21.51, 95% CI 16.35-28.32) times compared to the baseline in the BBIBP-CorV and the RCP vaccine groups. Geometric mean ratios (GMR) and 95% CI for serum neutralizing antibody titers for RCP compared with BBIBP-CorV on days 14, 90, and 180 were 6.81 (5.32-8.72), 1.77 (1.15-2.72), and 2.37 (1.62-3.47) respectively. We observed a similar pattern for specific antibody responses against S1 and RBD. We detected a rise in gamma interferon (IFN-γ), tumor necrosis factor (TNF-α), and interleukin 2 (IL-2) following stimulation with S antigen, particularly in the RCP group, and the flow cytometry examination showed an increase in the percentage of CD3 + /CD8 + lymphocytes. RCP and BBIBP-CorV had similar safety profiles; we identified no vaccine-related or unrelated deaths. CONCLUSIONS: BBIBP-CorV and RCP vaccines as booster doses are safe and provide a strong immune response that is more robust when the RCP vaccine is used. Heterologous vaccines are preferred as booster doses. TRIAL REGISTRATION: This study was registered with the Iranian Registry of Clinical Trial at www.irct.ir , IRCT20201214049709N4. Registered 29 November 2021.

Did the COVID-19 pandemic change the weight reduction in patients with obesity after bariatric surgery?

BACKGROUND: The COVID-19 pandemic has significantly impacted healthcare services worldwide, including bariatric surgery. There is a concern that the pandemic-induced stay-at-home orders and social restrictions may negatively affect weight reduction outcomes post-bariatric surgery. This study aimed to examine the impact of the COVID-19 on weight loss up to six months after three types of bariatric surgeries including One-Anastomosis Gastric Bypass (OAGB), RY Gastric Bypass (RYGB), and Sleeve Gastrectomy (SG) before and two time periods during the COVID-19 pandemic. METHODS: We conducted a retrospective study using data from a comprehensive database of bariatric surgery patients in Iran. We recruited 882 patients who underwent bariatric surgery from the initiation of COVID-19 to 6 months before public vaccination (Time period 3); among them, 311 patients underwent surgery in the first six months of the pandemic (Time period 2). These patients were compared with 1368 ones in the control group who completed their 6 months follow-up before the pandemic. The study compared the BMI reduction, excess weight loss (EWL), and total weight loss (TWL) outcomes between these groups using Generalized Estimating Equations (GEE) with gamma distribution to adjust for factors that were unevenly distributed across the groups. RESULTS: The age of participants in time periods 2 and 3 had a mean (standard deviation) of 38.97 (10.99) and 38.84 (10.71), respectively. In all groups, the majority of patients were females, accounting for 76.02%, 71.06%, and 75.74% for the control group and time periods 2 and 3, respectively. There was no significant difference between the groups in terms of weight reduction, as measured by BMI reduction, EWL, and TWL (related P values: 0.283, 0.465 and 0.169). Regression analysis indicated that higher baseline BMI values were associated with greater BMI reduction (0.04, 95% CI: 0.03-0.05), but this did not translate to higher EWL or TWL. Males showed greater BMI reduction (0.33, 95% CI: 0.18-0.49) and EWL (1.58, 95% CI: 0.79-2.37) than females, while females achieved higher TWL compared to males. Among different types of surgery, the OAGB resulted in more weight reduction among patients in the study. CONCLUSION: In conclusion, our study reveals that bariatric surgery remains effective for weight reduction during the first 6 months of the pandemic in Iran. Implementation of pandemic protocols ensures comparable efficacy to non-pandemic times. However, caution is needed in generalizing results beyond our specific context due to study limitations. Further research is essential to comprehensively assess the pandemic's broader impact on bariatric surgery outcomes under varying conditions.

A fludarabine and melphalan reduced-intensity conditioning regimen for HSCT in fifteen chronic granulomatous disease patients and a literature review.

Chronic granulomatous disease (CGD) is a life-threatening immunodeficiency condition. To date, hematopoietic stem cell transplantation (HSCT) is the only curative modality. We prospectively studied the outcomes of fifteen CGD patients undergoing HSCT with fludarabine and melphalan plus anti-thymocyte globulin (ATG). Most of the donors were fully matched siblings (n = 12). Cyclosporine A and methylprednisolone were used for graft-versus-host disease (GVHD) prophylaxis. CGD diagnosis had been suspected upon clinical symptoms and was confirmed in all patients by an abnormal neutrophil functional assay. The three-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 46.7%, respectively. With the median follow-up time of 33.12 months, the mean OS and EFS were 42.6 and 26.8 months; respectively. Eleven patients (73.33%) achieved full donor chimerism. Two stable mixed chimerisms with no sign of the underlying disease (13.33%) and two secondary graft failure (13.33%) occurred as well. The cumulative incidence of transplant-related mortality was 23.1% and it was two times more in adults compared with children. Three years GVHD-FS (free survival) was 57.8% in all patients and it was 70% and 42.9% in children and adults, respectively. Our results indicate that fludarabine, melphalan, and ATG have relatively favorable outcomes in CGD patients. Also, we suggest that HSCT should be performed as soon as a suitably matched donor is found.

The efficacy of corticosteroids therapy in patients with moderate to severe SARS-CoV-2 infection: a multicenter, randomized, open-label trial.

BACKGROUND: We performed a multicenter, randomized open-label trial in patients with moderate to severe Covid-19 treated with a range of possible treatment regimens. METHODS: Patients were randomly assigned to one of three regimen groups at a ratio of 1:1:1. The primary outcome of this study was admission to the intensive care unit. Secondary outcomes were intubation, in-hospital mortality, time to clinical recovery, and length of hospital stay (LOS). Between April 13 and August 9, 2020, a total of 336 patients were randomly assigned to receive one of the 3 treatment regimens including group I (hydroxychloroquine stat, prednisolone, azithromycin and naproxen; 120 patients), group II (hydroxychloroquine stat, azithromycin and naproxen; 116 patients), and group III (hydroxychloroquine and lopinavir/ritonavir (116 patients). The mean LOS in patients receiving prednisolone was 5.5 in the modified intention-to-treat (mITT) population and 4.4 days in the per-protocol (PP) population compared with 6.4 days (mITT population) and 5.8 days (PP population) in patients treated with Lopinavir/Ritonavir. RESULTS: The mean LOS was significantly lower in the mITT and PP populations who received prednisolone compared with populations treated with Lopinavir/Ritonavir (p = 0.028; p = 0.0007). We observed no significant differences in the number of deaths, ICU admission, and need for mechanical ventilation between the Modified ITT and per-protocol populations treated with prednisolone and Lopinavir/Ritonavir, although these outcomes were better in the arm treated with prednisolone. The time to clinical recovery was similar in the modified ITT and per-protocol populations treated with prednisolone, lopinavir/ritonavir, and azithromycin (P = 0.335; P = 0.055; p = 0.291; p = 0.098). CONCLUSION: The results of the present study show that therapeutic regimen (regimen I) with low dose prednisolone was superior to other regimens in shortening the length of hospital stay in patients with moderate to severe COVID-19. The steroid sparing effect may be utilized to increase the effectiveness of corticosteroids in the management of diabetic patients by decreasing the dosage.

Comparative Analysis of Mortality Rates among Morbidly Obese Individuals: A Study of Patients Undergoing Bariatric Surgery, Nonsurgical Morbidly Obese Individuals, and the General Population.

INTRODUCTION: Mortality decreases following bariatric surgery. We explored the extent of the reduction and whether or not it reaches the general population level in a large cohort of patients with obesity. This study aimed to compare all-cause mortality between patients with obesity who undergo bariatric surgery and those who do not, with the general Iranian population during the same period. METHOD: Data from Iran's National Obesity Surgery Database were used to establish a large cohort of patients registered between 2009 and 2019. The current vital status of the patients was determined by utilizing post-surgery follow-up data for those who underwent the operation. For patients without a surgery record, a predefined checklist was filled out through telephone interviews. Death data from the National General Registrar's office were obtained for all cohort members. RESULTS: Of 13,313 cohort members, 12,915 were eligible for analysis. The median age at the first visit was 38 years, and 78% were women. 6,190 patients (47.9%) underwent bariatric surgery, and 6,725 patients (52.1%) were not yet operated on at the time of analysis. We observed 139 deaths during 53,880 person-years follow-ups. The median follow-ups for operated-on and not operated-on groups were 4 and 4.8 years. The mortality rates among nonoperated patients were 2.89 times higher (standardized mortality ratio [SMR] = 2.89, 95% CI: 2.36-3.53) than those in the general population, while in operated patients, the mortality rate decreased to 1.82 as high (SMR = 1.82, 95% CI: 1.34-2.46). CONCLUSION: The risk of death has been diminished in the operated-on group. It still remains considerably higher than the risk in the general population.

Five-Year BAROS Score Outcomes for Roux-en-Y Gastric Bypass, One Anastomosis Gastric Bypass, and Sleeve Gastrectomy: a Comparative Study.

PURPOSE: Metabolic and bariatric surgery (MBS) has been shown to enhance the quality of life (QoL) in individuals with obesity. The Bariatric Analysis and Reporting Outcome System (BAROS) is a highly reliable scoring system utilized to assess weight loss, obesity-associated medical conditions, and QoL following MBS. This study aimed to assess the efficacy of sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and one anastomosis gastric bypass (OAGB) in improving health outcomes for individuals with severe obesity, employing the BAROS questionnaire. METHODS: A retrospective study was conducted, enrolling 299 patients with a body mass index (BMI) of 40 or higher who had undergone primary MBS (RYGB, OAGB, or SG) and had a 5-year follow-up. Patients were evaluated using the BAROS scoring system, which included measures of % excess weight loss (%EWL), improvement and remission of obesity-related medical problems, and postoperative short-term and long-term complications. RESULTS: The mean age and pre-op BMI of the patients was 39.4 ± 9.4 years and 44.6± 6.5 kg/m2, respectively. The total BAROS score was significantly higher in patients who underwent OAGB compared to those who underwent RYGB and SG (P, 0.02). However, no significant differences were observed in other aspects of the BAROS score, such as QoL. CONCLUSION: This study demonstrated that all three common metabolic and bariatric surgical procedures (SG, RYGB, and OAGB) significantly improved the QoL after surgery. Furthermore, patients who underwent OAGB had a significantly higher total BAROS score at the 5-year follow-up compared to those who underwent RYGB and SG.

Safety and efficacy of RCP recombinant spike protein covid-19 vaccine compared to Sinopharm BBIBP: A phase III, non-inferiority trial.

Background: We conducted a phase III, non-inferiority trial comparing safety and efficacy of RCP recombinant spike protein Covid-19 vaccine to BBIBP (Sinopharm). Methods: Adult Iranian population received RCP or BBIBP in a randomized, double blind and an additional non-randomized open labeled trial arms. Eligible participants signed a written informed consent and received two intramuscular injections three weeks apart. In the randomized arm, an intranasal dose of vaccine or adjuvant-only preparation were given to the RCP and BBIBP recipients at day 51 respectively. Participants were actively followed for up to 4 months for safety and efficacy outcomes. Primary outcome was PCR + symptomatic Covid-19 disease two weeks after the second dose. The non-inferiority margin was 10% of reported BBIBP vaccine efficacy (HR = 1.36). Results: We recruited 23,110 participants (7224 in the randomized and 15,886 in the non-randomized arm). We observed 604 primary outcome events during 4 months of active follow-up including 121 and 133 in the randomized and 157 and 193 cases in the non-randomized arms among recipients of RCP and BBIBP respectively. Adjusted hazard ratios for the primary outcome in those receiving RCP compared with BBIBP interval were 0.91 (0.71-1.16) and 0.62 (0.49-0.77) in the randomized and non-randomized arms respectively. The upper boundary of 99.1% confidence interval of HR = 0.91 (0.67-1.22) remained below the margin of non-inferiority in the randomized arm after observing the early stopping rules using O'Brien Fleming method. Conclusion: Our study showed that the RCP efficacy is non-inferior and its safety profile is comparable to the BBIBP.

Determinants of Patient's Adherence to the Predefined Follow-up Visits After Bariatric Surgery.

INTRODUCTION: Multidisciplinary care after bariatric surgery is essential for long-term safety and optimal weight loss. However, many patients do not participate in routine postoperative follow-ups. We have explored the determinants of patients' adherence to scheduled follow-up visits after bariatric surgery. METHOD: A retrospective cohort study was performed on patients who underwent bariatric surgery from 2009 to 2019. Cohort participants with a proportion of attendance above the median were compared with those below the median in the first-year post-operation and the period after that. We assumed that the contribution of each predefined session to the overall attendance at eligible sessions is not equal. We weighted each predefined session by the proportion of attendance of all cohort members scheduled for that session. We then calculated the proportion of attendance for each individual at each period. Discriminatory logistic regression was used to identify factors separating adherers from non-adherers. RESULTS: We followed 5245 patients who underwent bariatric surgery for up to 10 years. The median follow-up was 2 years. Patients with the following characteristics were more likely to comply with the postoperative attendance schedule: female sex, older age, higher body mass index at the first visit, non-smoker, readmission after surgery, being operated in a general hospital, and one-anastomosis gastric bypass (OAGB) or Roux-en-Y gastric bypass (RYGB) surgery type. Comorbidities did not significantly affect patients' adherence to the predefined follow-up schedules. CONCLUSION: Younger male smokers are more likely non-adherers. Patients with comorbidities are not at an increased risk of missing predefined postoperative follow-up visits.

A Representative Percentile Chart for Prediction of Weight Loss Trend after Sleeve Gastrectomy.

INTRODUCTION: It could be valuable for surgeons and patients to use one chart in different groups and evaluate weight loss during the post-surgery period. METHODS: This retrospective study used the Iran National Obesity Surgery Database. Patients with clinically severe obesity aged 18-70 undergoing sleeve gastrectomy participated in this study. Body mass index (BMI) reduction and 5 other metrics measured over the study period were modeled using lambda-mu-sigma method. Our data were split into the train (70%) and test (30%) sets. RESULTS: In this study, 1,258 patients (75% female) met the eligibility criteria to participate. Mean age and initial BMI were 36.87 ± 10.51 and 42.74 (40.37-46.36), respectively. Percentile charts for various metrics have been presented for the first 2 years after surgery. CONCLUSIONS: For sleeve surgery, all metrics are acceptable for clinical applications. Using the statistical view, BMI reduction is the most acceptable metric according to the lowest bias values and its variation between all the metrics.

Weight Reduction Percentile Charts: 2-Year Follow-up Results of OAGB and RYGB Post Bariatric Surgery.

PURPOSE: Using a single percentile chart provides us with high standards for the evaluation and accurate investigation of sufficient weight loss after bariatric surgery, counseling, and treating patients in an evidence-based way. Creating percentile charts of weight loss for gastric bypass is the aim of this study. MATERIALS AND METHODS: This retrospective study was based on data from patients who underwent RYGB or OAGB from February 2008 to February 2020. The lambda-mu-sigma (LMS) method was used to estimate the reduction in body mass index (BMI) and six other metrics measured throughout post-operative follow-up. Percentile charts for various metrics have been presented for the first 2 years' post-surgery. We applied a bootstrap sampling method to evaluate percentile validity. RESULTS: We recruited 2579 and 1943 patients who underwent OAGB (75% female) and RYGB (84% female) and were between the ages of 18 and 70 years. The preoperative BMI of patients in the OAGB group was higher than in the RYGB group. Concerning RYGB weight reduction results, the maximum percentage of excess weight loss (%EWL) occurs 18 months after surgery and is steady at 24 months. Far above 50%, EWL is achieved after 6 months. OAGB weight loss follows the same trend as RYGB; at 6 months, the %EWL values are slightly higher than RYGB. CONCLUSIONS: We present the first bariatric weight loss percentile chart for OAGB. It allows evaluation of sufficient and insufficient weight loss at any post-operative point in a visual aspect. Furthermore, it predicts prospective outcomes and guides patient monitoring.

Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial.

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46-23.13), 11.12 (2.74-45.09), and 20.70 (5.05-84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27-25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18-70 Years; A Randomized, Double-Blind Clinical Trial.

BACKGROUND: This study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. METHOD: In a randomized, double-blind, placebo-controlled trial, adults aged 18-70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. RESULT: Between May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02-6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. CONCLUSION: RCP vaccine is safe and creates strong and durable humoral and cellular immunity. TRIAL REGISTRATION: (IRCT20201214049709N2).

ABO Incompatibility and Hematopoietic Stem Cell Transplantation Outcomes.

Introduction: The increased risk of hemolytic reactions and erythrocyte recovery delay in ABO incompatible hematopoietic stem cell transplantation (HSCT) are well established. Effects of ABO incompatibility on other transplantation outcomes are evaluated in this study. Subjects and Methods: We prospectively followed 501 patients undergoing allogeneic stem cell transplantation regarding their ABO compatibility groups for a median time of 34.7 months. Patients were studied in minor, major and bidirectional mismatched and matched groups. Results: Mean survival time (OS) was lower in minor mismatched group (p-value= 0.017). Minor and bidirectional mismatched groups received significantly more packed cell units than matched group (p-value < 0.0001 and p-value =0.002, respectively).Mean number of platelet unit infusion was significantly more in major mismatched recipients than matched group (p- value=0.031). Death rate was much more than expected in minor mismatched group. Two cases of PRCA (pure red cell aplasia) were found in major mismatched group. No statistically significant difference was found in the incidence of acute GVHD, chronic GVHD, time to neutrophil recovery, relapse- free survival, non-relapse mortality and relapse rate among groups. Conclusion: In order to prevent complications of ABO-incompatible SCT such as decrease in OS and the need for more transfusions, choosing ABO-compatible donors would improve transplantation outcomes.

How Do Donor-Recipient CMV Serostatus and Post-Hematopoietic Stem Cell Transplantation CMV Reactivation Affect Outcomes in Acute Leukemia Patients?

Background: This study evaluated CMV serostatus in donors and recipients of hematopoietic stem cell transplantation (HSCT) and its effects on CMV reactivation of patients and all aspects of CMV on HSCT outcomes. Materialsand Methods: Seven hundred and five adult acute leukemia patients (AML=408 and AML=297) who had undergone HSCT were included in this retrospective study. We categorized donor-recipient pairs in three risk groups: positive donors (D+) were studied as high-risk group, including either R+ or R-(n=485), R-D- as low-risk group (n=32) and R+D- as intermediate group (n=15). Results: There was no statistically difference in CMV reactivation among these risk groups (P=0.14).CMV infection rate was lower in R+D+ than R+D-(p=0.050). Multivariate analysis showed that patients developing CMV infection had lower overall survival (p=0.04, HR: 1.43, CI=1.00- 2.05) and higher non- relapse mortality (P=0.01, HR: 1.62, CI=1.11-2.38). Relapse rate did not change in CMV reactivated patients (P=0.94). Conclusion: The results of the study indicated that asCMV reactivation occurred more in R+D- patients compared to R+D+ ones, and was associated with inferior OS and higher NRM it could be suggested that in contrast to general belief, if the recipient is seropositive , seropositive donor is preferred to a seronegative one.