Nevin Manimala

J Cancer Res Clin Oncol. 2023 Jan 3. doi: 10.1007/s00432-022-04563-4. Online ahead of print.

ABSTRACT

BACKGROUND: Bevacizumab (Avastin^®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, Avastin^® has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with Avastin^® sourced from the EU (bevacizumab-EU), in patients with non-squamous non-small cell lung cancer (nsNSCLC).

METHOD: In this randomized, double-blind, multicenter, phase III similarity study, treatment naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin^® groups. Patients received TAB008 or Avastin^® 15 mg/kg intravenously plus paclitaxel/carboplatin for 4-6 cycles followed by TAB008 or Avastin^® 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression-free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady-state pharmacokinetics.

RESULTS: A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin^® group). In the full analysis set, ORRs were 55.957% for TAB008 and 55.720% for Avastin^®, and the ORR ratio was 1 (90% CI 0.89-1.14), well within the predefined equivalence margin of 0.75-1.33. No significant differences were found in DCR within 6 cycles (95.703% vs 95.367%, p = 0.8536), DoR (8.17 vs 7.3 months, p = 0.3526), PFS (9.10 vs. 7.97 months, p = 0.9457), 1 year overall survival rate (66.2% vs 68%, p = 0.6793), or OS (20.4 vs 17.6 months, p = 0.6549). Serious adverse events (SAEs) occurred in 37.55% (104/277) of patients in the TAB008 group and 34.32% (93/271) in the Avastin^® group. Anti-drug antibodies were reported in 3 of 277 (1.08%) TAB008 patients, and 5 of 271 (1.85%) Avastin^® patients, neutralizing antibody (Nab) was positive in 1 patient on Avastin^®, which became negative upon follow-up. The steady-state trough concentrations (C_ssmin) were 106.13 μg/mL in TAB008 group and 96.03 μg/mL in Avastin^® groups, with the treatment group ratio of LS geometric means fully contained within the bioequivalence limits of 80.00-125.00% (90% CI was 101.74-120.05%).

CONCLUSIONS: TAB008 is similar to Avastin^® in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity.

TRIAL REGISTRATION: ClinicalTrials.gov number; NCT05427305.

PMID:36595042 | DOI:10.1007/s00432-022-04563-4

Med Microbiol Immunol. 2023 Jan 3. doi: 10.1007/s00430-022-00759-0. Online ahead of print.

ABSTRACT

Measurement of anti-pneumococcal capsular polysaccharides (anti-PnPs) IgG titers is an important tool in the immunologic assessment of patients with suspected immunodeficiency disorders (ID) to reduce the morbi-mortality and minimize severe infections. Retrospectively, we studied the relationship among anti-PnPs IgG response to 3 doses of Prevenar®13, levels of immune system components, leukocyte populations, and clinical data in children with ID. Serum samples were collected at least 4 weeks post vaccination. Subsequently, multi-serotype enzyme-linked immunosorbent assay (ELISA) was performed. Eighty-seven children (under 12 years) were enrolled. Primary immunodeficiency disorder (PID) was the most common disorder (45) followed by possible immunodeficiency disorder (POID) (19), secondary immunodeficiency disorder (SID) (15), and mixed immunodeficiency disorder (MID) (8). The median age was 3 (1.50-5.33) years, 65% of patients were male. Deficient production of anti-PnPs IgG (titer ≤ 50 mg/L) was detected in 47 patients (54%), especially in the MID group, all of them under immunosuppressive therapy. In PCV13 responders, the mean of leukocyte population levels was higher with statistically significance differences in CD4 + /CD8 + T lymphocytes (p = 0.372, p = 0.014) and CD56 + /CD16 + NK (p = 0.016). Patients with previous bone marrow transplantation were the worst PCV13 responders. Pneumococcal IgG antibody titers (post-vaccination) along with clinical and analytical markers represented.

PMID:36595027 | DOI:10.1007/s00430-022-00759-0

Eur J Cardiovasc Nurs. 2023 Jan 3:zvad005. doi: 10.1093/eurjcn/zvad005. Online ahead of print.

ABSTRACT

AIM: Reduction of blood pressure and improvement of stress and sleep disorders in patients with essential hypertension were important factors. Auricular acupressure was an appropriate complementary therapy for the elderly with essential hypertension for whom pharmacological therapy was not available.

METHODS AND RESULTS: This study was a single-blind, randomized, placebo-controlled study. The experimental group (n = 23) received 8 weeks of auricular acupressure intervention on specific acupoints (superior triangular fossa, Shenmen, kidney, heart, occiput) related to blood pressure, pulse rate, stress, and sleep, whereas the control group (n = 23) received auricular acupressure on nonspecific acupoints. The primary outcomes were the systolic and diastolic blood pressure measured weekly. The secondary outcomes were the pulse rate, heart rate variability, actigraphy measured through Fitbit, and the PSQI were measured before and after the experiment. There were statistically significant differences in systolic blood pressure (F = 5.67, p = .022), diastolic blood pressure (17.53, p < .001), and pulse rate (F = 6.78, p = .013) over time. Stress index (χ2 = 2.12, p = .040) and sleep efficiency (χ2 = 3.57, p = .001) were also significantly different before and after the experiment. However, there was no significant difference in the Pittsburgh Sleep Quality Index.

CONCLUSION: The findings showed that auricular acupressure leads to improvements in blood pressure, stress, and sleep in elderly people with essential hypertension. Therefore, auricular acupressure can be used as an alternative nursing intervention for hypertension prevention, stress, and sleep management.

REGISTRATION: WHO ICTRP KCT0007364.

PMID:36594992 | DOI:10.1093/eurjcn/zvad005

Am J Primatol. 2023 Jan 3:e23463. doi: 10.1002/ajp.23463. Online ahead of print.

ABSTRACT

The self-initiated split of a social group, known as fission, is a challenge faced by many group-living animals. The study of group fission and the social restructuring process in real time provides insights into the mechanism of this biologically important process. Previous studies on fission in Japanese macaques (Macaca fuscata) assigned individuals to newly reorganized groups mainly using behavioral observations and group attendance records based on periods before or after fission itself. Here, we present a novel framework for group classification during the process of fission that uses quantifiable behavioral variables and statistical analyses. The framework was tested on a group fission process at Affenberg Landskron (Austria), a park that housed around 160 semi-free-ranging Japanese macaques. The behavioral data were collected for 26 days during fission. We analyzed three behavioral developments recurrent in fissions in Japanese macaques, that is, independence of behavior, participation in group movements, and separation of nomadic ranges. These analyses were combined to assign individuals to different groups. Our study resulted in one main group (N = 33), one subgroup (N = 36) and 56 individuals whose group membership was still undefined. The demographic characteristics of these newly formed groups were comparable with those of fissioned groups in wild populations. Furthermore, we found that these newly forming groups showed early social dynamics of fission five months before group level movements, that is: grouping based on spatial proximity and spatial withdrawal of the subgroup to the periphery. These results underline the validity of our novel framework to study social dynamics in Japanese macaques during the process of fission. It represents an important addition to existing methods, and we recommend testing its scope in other primate societies.

PMID:36594448 | DOI:10.1002/ajp.23463

Magn Reson Med. 2023 Jan 3. doi: 10.1002/mrm.29576. Online ahead of print.

ABSTRACT

PURPOSE: To increase the effectiveness of respiratory gating in radial stack-of-stars MRI, particularly when imaging at high spatial resolutions or with multiple echoes.

METHODS: Free induction decay (FID) navigators were integrated into a three-dimensional gradient echo radial stack-of-stars pulse sequence. These navigators provided a motion signal with a high temporal resolution, which allowed single-spoke binning (SSB): each spoke at each phase encode step was sorted individually to the corresponding motion state of the respiratory signal. SSB was compared with spoke-angle binning (SAB), in which all phase encode steps of one projection angle were sorted without the use of additional navigator data. To illustrate the benefit of SSB over SAB, images of a motion phantom and of six free-breathing volunteers were reconstructed after motion-gating using either method. Image sharpness was quantitatively compared using image gradient entropies.

RESULTS: The proposed method resulted in sharper images of the motion phantom and free-breathing volunteers. Differences in gradient entropy were statistically significant (p = 0.03) in favor of SSB. The increased accuracy of motion-gating led to a decrease of streaking artifacts in motion-gated four-dimensional reconstructions. To consistently estimate respiratory signals from the FID-navigator data, specific types of gradient spoiler waveforms were required.

CONCLUSION: SSB allowed high-resolution motion-corrected MR imaging, even when acquiring multiple gradient echo signals or large acquisition matrices, without sacrificing accuracy of motion-gating. SSB thus relieves restrictions on the choice of pulse sequence parameters, enabling the use of motion-gated radial stack-of-stars MRI in a broader domain of clinical applications.

PMID:36594436 | DOI:10.1002/mrm.29576

J Geriatr Psychiatry Neurol. 2023 Jan 3:8919887221149142. doi: 10.1177/08919887221149142. Online ahead of print.

ABSTRACT

INTRODUCTION: Older adults have one of the highest age-specific suicide rates in France, and the risk of suicide is higher for those living in nursing homes. The aim of our study was to assess the effectiveness of gatekeeper training for nursing home staff on the knowledge and stigmas towards suicidal crisis and the impact on suicidal behaviour rates.

METHOD: A total of 427 nursing or administrative staff from 110 nursing homes received gatekeeper training in the Hauts-de-France French region between September 2016 and June 2018. First, knowledge and stigmas on suicidal crisis were assessed through a pretest and posttest survey. Second, a retrospective survey was conducted to determine suicide behaviour rates before and after training in nursing homes. Then, changes between pre- and posttraining scores and suicide rates were evaluated with a paired samples T test and rate difference calculation (P value of <0.05 was considered statistically significant).

RESULTS: A total of 315 trainees completed the questionnaires on knowledge and stigmas related to suicidal crisis, and we found a significant difference in the total scores (P < 0.01). Moreover, we found a significant decrease in the incidence of suicide attempts (SAs) after training (P = 0.002), but the incidence of deaths by suicide was not significantly different prior to and after the training course (P = 0.46).

CONCLUSION: We highlighted an improvement in knowledge and stigmas after training and a reduction in the rates of SAs with our gatekeeper suicide prevention program. Future research is needed to improve suicide prevention for nursing home residents.

PMID:36594410 | DOI:10.1177/08919887221149142

Ann Med. 2023 Dec;55(1):285-291. doi: 10.1080/07853890.2022.2160491.

ABSTRACT

BACKGROUND: The exhaustive information about non-communicable diseases associated with COVID-19 and severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) are getting easier to find in the literature. However, there is a lack of knowledge regarding tuberculosis (TB) and chronic obstructed pulmonary disease (COPD), with numerous infections in COVID-19 patients.

OBJECTIVES: Priority is placed on determining the patient’s prognosis based on the presence or absence of TB and COPD. Additionally, a comparison is made between the risk of death and the likelihood of recovery in terms of time in COVID-19 patients who have either COPD or TB.

METHODOLOGY: At the DHQ Hospital in Muzaffargarh, Punjab, Pakistan, 498 COVID-19 patients with TB and COPD were studied retrospectively. The duration of study started in February 2022 and concluded in August 2022. The Kaplan-Meier curves described time-to-death and time-to-recovery stratified by TB and COPD status. The Wilcoxon test compared the survival rates of people with TB and COPD in two matched paired groups and their status differences with their standard of living.

RESULTS: The risk of death in COVID-19 patients with TB was 1.476 times higher than in those without (95% CI: 0.949-2.295). The recovery risk in COVID-19 patients with TB was 0.677 times lower than in those without (95% CI: 0.436-1.054). Similarly, patients with TB had a significantly shorter time to death (p=.001) and longer time to recovery (p=.001).

CONCLUSIONS: According to the findings, the most significant contributor to an increased risk of morbidity and mortality in TB and COPD patients was the COVID-19.KEY MESSAGESSARS-Cov-19 is a new challenge for the universe in terms of prevention and treatment for people with tuberculosis and chronic obstructive pulmonary disease, among other diseases.Propensity score matching to control for potential biases.Compared to hospitalized patients with and without (TB and COPD) had an equivalently higher mortality rate.

PMID:36594409 | DOI:10.1080/07853890.2022.2160491

Int J Urol. 2023 Jan 3. doi: 10.1111/iju.15138. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the relation between serum zinc concentration and several factors, including serum testosterone concentration and the score of questionnaires on sexual function in patients with sexual problems.

METHODS: This study comprised 720 men (age, 46.3 [21-83] years) with some kind of sexual problem. Age, scores of the Sexual Health Inventory for Men and the Erection Hardness Score, and endocrinologic data including serum concentrations of testosterone, prostate-specific antigen, and zinc were included in this study. After serum zinc concentration of the men was classified into 5 groups (<70, 70≤ <80, 80≤ <90, 90≤ <100, ≤100 μg/dl), the relation of each parameter with serum zinc concentration was assessed for a trend analysis. Finally, the relation between serum concentrations of zinc and testosterone as well sexual function evaluated by the scores of the questionnaires was investigated.

RESULTS: Only serum testosterone concentration (ptrend = 0.028) and serum cortisol concentration (ptrend = 0.003) showed a statistically significant relation to serum zinc concentration by trend analysis. Interestingly, trend analysis between serum concentrations of testosterone and zinc still showed a significant association after adjustment for serum cortisol concentration (ptrend = 0.032). However, no significant association was found in the relation between serum zinc concentration and the scores of the questionnaires after adjustment for serum concentrations of testosterone and cortisol.

CONCLUSION: We clearly showed that after adjustment for serum cortisol concentration by trend analysis, serum testosterone concentration decreased as serum zinc concentration decreased, although sexual symptoms were not associated with this decrease.

PMID:36594398 | DOI:10.1111/iju.15138

Mymensingh Med J. 2023 Jan;32(1):236-239.

ABSTRACT

The success of an endodontic therapy is combinational, dependent on mechanical preparation of canal and chemically detriment of microbial load. Therefore the use of an efficient irrigant is necessary having potential for eradicating the population dependent endodontic microbes. The main aim of the study was to evaluate and compare the antimicrobial potential of commonly used endodontic irrigants and LED light activated curcumin against the endodontic microbial variants of Saudi Arabian population. The 170 infected pulp samples were collected in nutrient broth and streaked on four types of agar plates for each sample after 24 hours of incubation at 37°C. Later after incubation for one day, the microbes were identified under the microscope and the number of microbial colonies. Using well method anti-microbial efficacy of three experimental groups with traditional endodontic irrigants (5.25% NaOCl, 2.0% CHX and 17.0% EDTA), LED light activated photosensitizer and one negative control (NaCl) was evaluated. The photosensitizer and 17.0% EDTA displayed to have efficient anti-microbial potential against E. fecalis and Streptococcal species reducing the colony count and increased radius of 4.3mm (Curcumin)/ 4.1mm (17.0% EDTA) and 3.2mm (Curcumin)/ 3.0mm (17.0% EDTA) showing anti-bacterial effect on the agar plates trailed by 5.25% NaOCl but statistically no significant difference was observed. On contrary 5.25% NaOCl showed strong potential against Staphylococcus and C. albicans species. Overall it can be concluded from the results 5.25% of NaOCl have stronger anti-microbial potential than 17.0% EDTA, CHX and NaCl against endodontic species of Saudi Arabian population.

PMID:36594326

Mymensingh Med J. 2023 Jan;32(1):177-184.

ABSTRACT

To assess the role of the Glasgow Comma Score (GCS) for predicting the outcome of the patient with fever and altered sensorium was the objective of the study. This prospective observational study was conducted for six months following ethical approval. Informed consent was obtained prior enrollment. A total of 50 patients with complaints of fever for <2 weeks duration with altered sensorium with or without seizure were included in the study. GCS was calculated for all patients just after admission and before starting interventions. All patients were investigated and managed according to the hospital protocol. The outcome of the patients (living or dead within the hospital) was evaluated against the admission GCS score. The study was performed in accordance with the current Declaration of Helsinki. Of all, 42.0% (n=21) of the patients had bacterial meningitis, followed by viral encephalitis, cerebral malaria and coma vigil. Complete recovery occurred in 60.0% of cases, while recovery with disability occurred in 28.0% of cases. Death occurred in 12.0% of cases (n=6) due to cerebral malaria, viral encephalitis and bacterial meningitis (n=2 each cause). A higher number of deaths occurred in the lower GCS group (n=5 in GCS group 3-5) and this difference was statistically significant (p<0.05). Moreover, considering death as an outcome, multivariate logistic regression showed that GCS (OR 70.598, 95% CI-1.243-4009.41; p=0.039) was an independent predictor of the outcome. GCS seemed to be a predictor of the short-term outcome of the patient presenting with fever and altered sensorium in our setting. However, further exploration in larger setting with appropriate study design is recommended.

PMID:36594318