Tag: nevin manimala

In Vivo. 2022 Nov-Dec;36(6):2884-2889. doi: 10.21873/invivo.13029.

ABSTRACT

BACKGROUND/AIM: This study investigated a correlation between ex vivo interferon-gamma (IFN)-gamma production using IFN-gamma releasing assay (IGRA) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) activity assessed by Birmingham vasculitis activity score (BVAS) in AAV patients.

PATIENTS AND METHODS: A total of 113 patients with AAV were consecutively selected from the AAV cohort and their medical records were reviewed. IGRA was performed at AAV diagnosis and before the initiation of glucocorticoids or immunosuppressive drugs for AAV treatment.

RESULTS: The median age was 61.8 years and 41.6% of the patients were men. Eighteen, 28, and 67 patients had EGPA, GPA, and MPA, respectively. Eighteen, 84, and 11 patients had positive, negative, and indeterminate results, and the median Nil, tuberculosis antigen, mitogen, and ex vivo IFN-gamma production were 0.1, 0.1, 10.0, and 9.8 IU/ml, respectively. There was no significant correlation between ex vivo IFN-gamma production and BVAS in AAV patients. When AAV patients were divided into two groups according to BVAS of 18, the higher tertile of BVAS, there was no significant difference in ex vivo IFN-gamma production between AAV patients with BVAS ≥18 and those without. In addition, there were no statistically significant correlations between ex vivo IFN-gamma production and BVAS in AAV patients with either indeterminate and negative IGRA results or only negative IGRA results.

CONCLUSION: There is no correlation between ex vivo IFN-gamma production and BVAS. This study provided information on the reliability of the IGRA results for latent tuberculosis screening in AAV patients regardless of the activity of AAV.

PMID:36309398 | DOI:10.21873/invivo.13029

In Vivo. 2022 Nov-Dec;36(6):2993-2998. doi: 10.21873/invivo.13044.

ABSTRACT

BACKGROUND/AIM: Bronchiectasis has long been neglected, unlike chronic obstructive pulmonary disease (COPD) and asthma. Recent clinical trials have shown that long-term use of azithromycin or erythromycin reduce exacerbations of non-cystic fibrosis (non-CF) bronchiectasis. Because of this, we should actively try to treat patients susceptible to severe status.

PATIENTS AND METHODS: We enrolled patients who had been diagnosed with bronchiectasis at five branches of the Catholic Medical Center between January 2015 to December 2017. We retrospectively analyzed these patients for demographic characteristics such as sex, age, body mass index (BMI), history of smoking and tuberculosis, bacterial colonization, pulmonary function, hospitalizations, and other exacerbations.

RESULTS: Colonization was shown to have a statistically significant association with hospitalization. A three-year follow up period showed that the mean frequency of hospitalization in patients without colonization was 0.8 times, compared to 0.7 times and 1.9 times, respectively in patients with NTM colonization and with other bacterial colonization (p-value=0.03). Patients with a lower BMI also had an increased risk of hospitalization (p-value=0.024). Current smokers had increased risk of mortality as compared to those who had never smoked (HR=11.29, p-value 0.015). Patients with a high BMI also had low risk of mortality as compared to patients with a low BMI (HR=0.76, p-value 0.005).

CONCLUSION: Patients with bronchiectasis having chronic colonization, low BMI, or who are current smokers tend to be at greater risk for severe illness. Therefore, physicians should actively treat these patients to prevent exacerbations and mortality.

PMID:36309393 | DOI:10.21873/invivo.13044

In Vivo. 2022 Nov-Dec;36(6):2708-2713. doi: 10.21873/invivo.13006.

ABSTRACT

BACKGROUND/AIM: The neonatal Fc receptor (FcRn) is a major histocompatibility class I-like molecule responsible for the transfer of passive humoral immunity from a mother to her newborn. Recent research revealed that FcRn is involved in antigen-presentation, humoral immunity and antitumor immunity of various types of cancer, such as lung, colon and breast. Lung cancer is the leading cause of cancer-related death and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer. NSCLC is a highly heterogeneous disease and this affects the prognosis. Therefore, many studies have tried to identify factors that are associated with prognosis. The lungs are a major organ expressing FcRn. We aimed to evaluate FcRn expression in surgical specimens of NSCLC and determine its correlation with patient prognosis.

MATERIALS AND METHODS: We analyzed 140 NSCLC surgical specimens for FcRn expression using immunohistochemistry and correlated positivity with clinicopathology and survival of these patients. A chi-squared test and Kaplan-Meier analysis with log-rank tests were performed for statistical evaluation.

RESULTS: The FcRn-positive group had a significantly higher disease-free survival and a tendency towards increased disease-specific survival in patients with tumor-node-metastasis stage I NSCLC.

CONCLUSION: Our study supports the hypothesis that FcRn down-regulation is associated with NSCLC progression.

PMID:36309388 | DOI:10.21873/invivo.13006

In Vivo. 2022 Nov-Dec;36(6):2630-2637. doi: 10.21873/invivo.12997.

ABSTRACT

BACKGROUND/AIM: Dedifferentiated liposarcoma (DDLS) is a type of soft-tissue sarcoma with a poor prognosis due to distant metastasis and resistance to chemotherapy. The antimalarial drug chloroquine (CQ) can induce apoptosis in cancer cells. CQ in combination with rapamycin (RAPA), an mTOR inhibitor, has shown efficacy on osteosarcoma and other types of cancer. In the present study the efficacy of RAPA combined with CQ on the treatment of a DDLS patient-derived orthotopic xenograft (PDOX) model was investigated.

MATERIALS AND METHODS: A patient-derived DDLS was transplanted into the left retroperitoneum of nude mice to establish a DDLS PDOX nude-mouse model. The mice were randomly divided as follows: untreated control group; CQ group; RAPA group; combined CQ and RAPA group (n=7 for all groups). During the treatment period, tumor volume was measured every 3-4 days with calipers. After 2 weeks treatment, the mice were sacrificed, and H&E staining was performed for histological evaluation. The TUNEL assay was performed to detect apoptosis.

RESULTS: The combination of CQ and RAPA arrested tumor growth in the DDLS PDOX compared to the untreated control (p=0.009) and was significantly more effective than RAPA alone (p=0.009). RAPA alone slowed tumor growth, but the difference was not statistically significant (p>0.05). CQ was not active alone (p>0.05). The number of apoptotic TUNEL-positive cells was significantly higher in the CQ plus RAPA group than in the other groups (p=0.02).

CONCLUSION: Combination therapy with CQ and RAPA arrested tumor growth in a DDLS PDOX model by inducing apoptosis.

PMID:36309387 | DOI:10.21873/invivo.12997

In Vivo. 2022 Nov-Dec;36(6):2986-2992. doi: 10.21873/invivo.13043.

ABSTRACT

BACKGROUND/AIM: To report long-term survival results after trimodal approach for locally advanced rectal cancer (LARC) in the Covid-19 era. We herein illustrate a clinical application of Covid-death mean-imputation (CoDMI) algorithm in LARC patients with Covid-19 infection.

PATIENTS AND METHODS: We analyzed 94 patients treated for primary LARC. Overall survival was calculated in months from diagnosis to first event (last follow-up/death). Because Covid-19 death events potentially bias survival estimation, to eliminate skewed data due to Covid-19 death events, the observed lifetime of Covid-19 cases was replaced by its corresponding expected lifetime in absence of the Covid-19 event using the CoDMI algorithm. Patients who died of Covid-19 (DoC) are mean-imputed by the Kaplan-Meier estimator. Under this approach, the observed lifetime of each DoC patient is considered as an “incomplete data” and is extended by an additional expected lifetime computed using the classical Kaplan-Meier model.

RESULTS: Sixteen patients were dead of disease (DoD), 1 patient was DoC and 77 cases were censored (Cen). The DoC patient died of Covid-19 52 months after diagnosis. The CoDMI algorithm computed the expected future lifetime provided by the Kaplan-Meier estimator applied to the no-DoC observations as well as to the DoC data itself. Given the DoC event at 52 months, the CoDMI algorithm estimated that this patient would have died after 79.5 months of follow-up.

CONCLUSION: The CoDMI algorithm leads to “unbiased” probability of overall survival in LARC patients with Covid-19 infection, compared to that provided by a naïve application of Kaplan-Meier approach. This allows for a proper interpretation/use of Covid-19 events in survival analysis. A user-friendly version of CoDMI is freely available at https://github.com/alef-innovation/codmi.

PMID:36309383 | DOI:10.21873/invivo.13043

In Vivo. 2022 Nov-Dec;36(6):2828-2834. doi: 10.21873/invivo.13021.

ABSTRACT

BACKGROUND/AIM: Body composition assessment has shown promising results as a prognostic biomarker as depicted by cross-sectional imaging of several tumor entities including lymphomas. The present study sought to elucidate the prognostic relevance of subcutaneous and visceral fat tissue (SAT and VAT) in patients with primary central nervous system lymphoma (PCNSL).

PATIENTS AND METHODS: Overall, 74 patients (36 female patients, 46.7%) with a mean age of 64.2±12.8 years (range=23-81 years) were identified in the database with sufficient clinical and imaging data and included into this retrospective study. Fat area assessment was performed on one axial slide on L3-height derived from staging computed tomography (CT) images. Subcutaneous, visceral, and intramuscular adipose tissues (SAT, VAT, IMAT) were estimated. Also, density of SAT, VAT, and IMAT were estimated. Finally, the ratio VAT/SAT (VSR) was calculated. Overall and progression-free survival (OS and PFS) were used as study end points.

RESULTS: In the observation period, overall, 47 patients (63.5%) died. Mean OS was 33.8±45.4 months and mean PFS was 26.6±42.7 months. The mean VAT value was 162±99.5 cm², the mean SAT was 202.4±103.3 cm², the mean VSR was 0.92±0.69. The hazard ratios (HRs) for overall survival were 0.87 for high VAT, 1.52 for SAT, and 0.73 for VSR in univariable analysis. For PFS it was 0.24 for VAT, 1.11 for SAT, and 1.07 for VSR. No values achieved statistical significance. Similar results were shown in Kaplan-Meier analysis for OS and PFS, respectively.

CONCLUSION: Parameters of adipose tissue are not associated with OS and PFS in patients with PCNSL.

PMID:36309379 | DOI:10.21873/invivo.13021

In Vivo. 2022 Nov-Dec;36(6):2662-2668. doi: 10.21873/invivo.13001.

ABSTRACT

BACKGROUND/AIM: Lesions in the seminal vesicle are described in the most used protocols for prostate cancer (PCa) induction. This study aimed to characterize the lesions of seminal vesicles associated with a protocol of PCa induction in rats to contribute to better characterization of this model.

MATERIALS AND METHODS: Forty-five male Wistar Unilever rats were randomly divided into two control groups: CONT1 (n=10) and CONT2 (n=10); and two PCa-induced groups: IND1 (n=10) and IND2 (n=15), sacrificed at 35 and 61 weeks, respectively. Animals from the induced groups were exposed to a multistep protocol for PCa induction. Animals, seminal vesicles and dorsolateral prostate were weighed. Seminal vesicles and dorsolateral prostate were submitted to histopathological and immunohistochemical analysis.

RESULTS: Animals in which PCa was induced had a lower mean body weight when compared with the control animals (p<0.05). The relative mean seminal vesicle weight was higher in groups with PCa when compared with control groups (p<0.05). Although the differences were not statistically significant, animals from the IND2 group developed more lesions than animals from the IND1 and CONT2 groups. It is worth noting that the animals from group IND2 developed papillary adenomas and carcinomas in situ, which were not observed in any other group. Similar to observations in seminal vesicles, animals from group IND2 developed more dorsolateral prostate lesions than animals from the IND1 group (p<0.05).

CONCLUSION: We observed that the longer the exposure to testosterone was, the greater was the incidence of preneoplastic and neoplastic lesions in both the seminal vesicle and the prostate, suggesting that testosterone exposure affects the spectrum of developed lesions.

PMID:36309374 | DOI:10.21873/invivo.13001

In Vivo. 2022 Nov-Dec;36(6):2918-2922. doi: 10.21873/invivo.13033.

ABSTRACT

BACKGROUND/AIM: The aim of this study was to determine the safety and efficacy of a direct-acting antiviral treatment, ombitasvir/paritaprevir/ritonavir and dasabuvir, without ribavirin, in a real-life setting.

PATIENTS AND METHODS: We performed a prospective observational study including 108 patients undergoing hemodialysis for end-stage kidney disease, referred to our clinic for antiviral therapy for chronic hepatitis C virus infection. Patients received treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, for 12 weeks. Sustained virologic response (SVR) was defined as undetectable viremia at 12 weeks after the end of therapy. For safety analysis, we monitored serum levels of hemoglobin, albumin, total bilirubin, alanine-aminotransferase and aspartate- aminotransferase at the beginning and end of therapy, as well as at SVR. Verbal Numeric Rating Scale was used to assess the presence of nausea, headaches and fatigue.

RESULTS: We noted a high prevalence of diabetic and hypertensive nephropathy as the underlying cause of chronic kidney disease. Most of the patients had F2 and F3 liver fibrosis (32.40% and 34.25%, respectively). The SVR rate was 96.2% (103/107 patients). We recorded an unrelated death after the completion of antiviral therapy. We found increased levels of nausea, headaches and fatigue at the end of therapy compared to at initiation, The presence and degree of symptoms did not correlate with the underlying cause of renal disease (p=0.72) nor with the degree of fibrosis (p=0.08). Minimal increases in transaminases and bilirubin were recorded at the end of treatment, with no statistical significance.

CONCLUSION: Oral antiviral therapy with ombitasvir/paritaprevir/ritonavir and dasabuvir can be safely used in hemodialysis patients, with similar response rates compared to the general population.

PMID:36309363 | DOI:10.21873/invivo.13033

JMIR Form Res. 2022 Oct 29. doi: 10.2196/41914. Online ahead of print.

ABSTRACT

BACKGROUND: Despite continuing efforts to improve inclusion of underserved groups in clinical research, gaps in diversity remain. Participation of special populations is especially important when facing problems of unprecedented complexity such as COVID-19. A better understanding of factors associated with immune response in diverse populations would advance future preventive and curative approaches.

OBJECTIVE: The objective of this study was to investigate the factors potentially responsible for adverse events following the COVID-19 immunization. The population of the study included adults from rural areas, developing countries, and those with medically understudied conditions, across a broad age range.

METHODS: The study evolved from peer-support networks developed during the COVID-19 pandemic. Participants were recruited digitally through online neighborhood and health communities. Some of the participants volunteered as study investigators assisting with off-line recruitment and safety monitoring. Individuals who consented to participate were asked to share their vaccination experiences either using constantly-evolving online surveys or via one-to-one communication. Inferential statistics to estimate differences between study groups was performed using parametric and non-parametric tests.

RESULTS: Of 1430 participants who shared their vaccination experiences, 648 had outcome measures at their 1.5-year follow-up. Statistically significant differences were found between age groups, types of vaccine adverse events (VAEs), incidences of breakthrough infections and health conditions linked to the microbiome. Pairwise comparisons showed that VAEs interfering with daily activities were significantly higher in both younger (18-59) and older groups (80-100, P < .001) when compared to the 60-79 age bracket. Short term VAEs were associated with lower incidence of breakthrough COVID-19 relative to those who reported either minimal or long-term adverse events (P < .001). A genetic origin was suggested for some adverse reactions.

CONCLUSIONS: The findings of this study demonstrate that vaccine adverse reactions in the elderly are being overlooked and the incidence of VAEs impairing immunity may be higher than previously thought. Better preventive measures are needed for all those at risk for life-threatening and long-term adverse events of vaccination. Supportive community-based studies focusing on these populations could add important data to the body of knowledge. Further and more comprehensive studies should follow.

CLINICALTRIAL: ClinicalTrials.gov NCT04832932; https://clinicaltrials.gov/ct2/show/NCT04832932.

INTERNATIONAL REGISTERED REPORT: RR2-10.1101/2021.06.28.21256779.

PMID:36309347 | DOI:10.2196/41914

World Neurosurg. 2022 Oct 26:S1878-8750(22)01490-5. doi: 10.1016/j.wneu.2022.10.073. Online ahead of print.

ABSTRACT

OBJECTIVE: Reported rates of failures varies greatly from below 5% up to over 50% and, no meta-analysis to assess the overall prevalence has ever been performed. Herein, the authors estimated the failure rate after internal CSF shunt (ICSFS) insertion and searched for associated factors.

METHODS: Six databases were searched from January 1990 to February 2022. Only original articles reporting the rate of adult shunt failure were included. Random-effects meta-analysis with generalised linear mixed model method and logit transformation was used to compute the overall failure prevalence. Subgroup analysis and meta-regression were implemented to search for associated factors.

RESULTS: Of 1,763 identified articles, 46 were selected, 70,859 ICSFS implantations and for 13,603 shunt failure, suggesting an accumulated incidence of 19.2%. However, the calculated pooled prevalence value and its 95% confidence interval (CI) were 22.7% _95%CI[19.8-5.8]. The CI of the different estimates did not overlap, indicating a strong heterogeneity confirmed by a high I² of 97.5%, _95%CI[97.1-97.8], p<0.001 with a τ²=0.3. Ninety-five percent prediction interval of shunt failure prevalence ranged from 8.75% up to 47.36%. A meta-regression of prevalence by year of publication found a barely significant decreasing failure rate of about two percent per year (-2.11, _95%CI[-4.02- -0.2], p-value=0.031).

CONCLUSION: Despite being a quite simple neurosurgical procedure, ICSFS insertion has one of the highest risk of complications with failure prevalence involving more than 1 patient out of 5. Nonetheless, all the efforts to lower these frustrating high level of shunt failure seem to be effective.

TRIAL REGISTRATION: This meta-analysis is registered in https://www.crd.york.ac.uk/PROSPERO/, PROSPERO ID: CRD42022339954.

PMID:36309337 | DOI:10.1016/j.wneu.2022.10.073