Tag: nevin manimala

Int J STD AIDS. 2023 May 5:9564624231173728. doi: 10.1177/09564624231173728. Online ahead of print.

ABSTRACT

BACKGROUND: Sexually transmitted infections pose a major public health challenge in the United States and this burden is especially acute in subpopulations like young men who have sex with men (YMSM) and young transgender women (YTW). Yet, the direct behavioral antecedents of these infections are not well understood making it difficult to identify the cause of recent increases in incidence. This study examines how variations in partnership rates and the number of condomless sex acts are associated with STI infections among YMSM-YTW.

METHOD: This study leveraged 3 years of data from a large longitudinal cohort of YMSM-YTW. A series of generalized linear mixed models examined the association between the number of condomless anal sex acts, number of one-time partners, number of casual partners, and number of main partners and chlamydia, gonorrhea, or any STI.

RESULTS: Results indicated the number of casual partners was associated with gonorrhea [aOR = 1.17 (95% CI: 1.08, 1.26)], chlamydia [aOR = 1.12 (95% CI: 1.05, 1.20)], and any STI [aOR = 1.14 (95% CI: 1.08, 1.21)] while the number of one-time partners was only associated with gonorrhea [aOR = 1.13 (95% CI: 1.02, 1.26)]. The number of condomless anal sex acts was not associated with any outcome.

CONCLUSION: These findings suggest the number of casual partners is a consistent predictor of STI infection among YMSM-YTW. This may reflect the quick saturation of risk within partnerships making the number of partners, rather than the number of acts, the more relevant factor for STI risk.

PMID:37146303 | DOI:10.1177/09564624231173728

Blood Transfus. 2023 Mar 10. doi: 10.2450/BloodTransfus.499. Online ahead of print.

ABSTRACT

BACKGROUND: Young adults form the majority of first-time blood donors to Australian Red Cross Lifeblood. However, these donors pose unique challenges for donor safety. Young blood donors, who are still undergoing neurological and physical development, have been found to have lower iron stores, and have higher risks of iron deficiency anaemia when compared to older adults and non-donors. Identifying young donors with higher iron stores may improve donor health and experience, increase donor retention, and reduce the burden on product donation. In addition, these measures could be used to individualise donation frequency.

MATERIALS AND METHODS: Stored DNA samples from young male donors (18-25 years; n=47) were sequenced using a custom panel of genes identified in the literature to be associated with iron homeostasis. The custom sequencing panel used in this study identified and reported variants to human genome version 19 (Hg19).

RESULTS: 82 gene variants were analysed. Only one of which, rs8177181, was found to have a statistically significant (p<0.05) association with plasma ferritin level. Heterozygous alleles of this Transferrin gene variant, rs8177181T>A, significantly predicted a positive effect on ferritin levels (p=0.03).

DISCUSSION: This study, identified gene variants involved in iron homeostasis using a custom sequencing panel and analysed their association with ferritin levels in a young male blood donor population. Additional studies of factors associated with iron deficiency in blood donors are required if a goal of personalised blood donation protocols is to be achieved.

PMID:37146293 | DOI:10.2450/BloodTransfus.499

Am Surg. 2023 May 5:31348231174003. doi: 10.1177/00031348231174003. Online ahead of print.

ABSTRACT

BACKGROUND: Over 20% of United States adolescents are obese. A thicker layer of subcutaneous adiposity might provide a protective “armor” layer against penetrating wounds. We hypothesized that adolescents with obesity presenting after isolated thoracic and abdominal penetrating trauma have lower rates of severe injury and mortality than adolescents without obesity.

METHODS: The 2017-2019 Trauma Quality Improvement Program database was queried for patients between 12 and 17 years old presenting with knife or gunshot wounds. Patients with body mass index (BMI) ≥30 (obese) were compared to patients with BMI <30. Sub-analyses were performed for adolescents with isolated abdominal trauma and isolated thoracic trauma. Severe injury was defined as an abbreviated injury scale grade >3. Bivariate analyses were performed.

RESULTS: 12,181 patients were identified; 1603 (13.2%) had obesity. In isolated abdominal gunshot or knife wounds, rates of severe intra-abdominal injuries and mortality were similar (all P > .05) between groups. In isolated thoracic gunshot wounds, adolescents with obesity had a lower rate of severe thoracic injury (5.1% vs 13.4%, P = .005) but statistically similar mortality (2.2% vs 6.3%, P = .053) compared to adolescents without obesity. In isolated thoracic knife wounds, rates of severe thoracic injuries and mortality were similar (all P > .05) between groups.

DISCUSSION: Adolescent trauma patients with and without obesity presenting after isolated abdominal or thoracic knife wounds had similar rates of severe injury, operative intervention, and mortality. However, adolescents with obesity presenting after an isolated thoracic gunshot wound had a lower rate of severe injury. This may impact the future work-up and management of adolescents sustaining isolated thoracic gunshot wounds.

PMID:37146266 | DOI:10.1177/00031348231174003

Am J Bot. 2023 May 5. doi: 10.1002/ajb2.16177. Online ahead of print.

ABSTRACT

PREMISE: The relative per-flower production of ovules and pollen varies broadly with angiosperm mating systems, with outcrossing types commonly producing more pollen grains per ovule than selfing types. The evolutionary causes of this variation are contentious, especially the relevance of pollination risk. Resolution of this debate may have been hampered by its focus on pollen:ovule (P:O) ratios rather than on the evolution of pollen and ovule numbers per se.

METHODS: Using published mean ovule and pollen counts, we analyzed associations with the proportion of removed pollen that reaches stigmas (pollen-transfer efficiency) and differences between pollinator-dependent and autogamous forms within and among species. Analyses involved Bayesian methods that simultaneously considered variation in pollen and ovule numbers and accounted for phylogenetic relatedness. We also assessed the utility of P:O ratios as mating-system proxies and their association with female outcrossing rates.

RESULTS: Median pollen number declined consistently with pollen-transfer efficiency among species, whereas median ovule number did not. Similarly, in both intraspecific and interspecific analyses, pollinator-dependent plants produced more pollen than autogamous plants, whereas ovule production did not differ statistically. Distributions of P:O ratios overlapped extensively for self-incompatible and self-compatible species and for different mating-system classes, and P:O ratios correlated weakly with outcrossing rate.

CONCLUSIONS: Our findings demonstrate that pollinator dependence and pollination efficiency commonly influence the evolution of pollen number per flower but have more limited effects on ovule number. P:O ratios provide ambiguous, possibly misleading, information about mating systems, especially when compared among clades. This article is protected by copyright. All rights reserved.

PMID:37146240 | DOI:10.1002/ajb2.16177

Cochrane Database Syst Rev. 2023 May 4;5:CD013798. doi: 10.1002/14651858.CD013798.pub2.

ABSTRACT

BACKGROUND: Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma (RCC) has changed fundamentally. Today, combined therapies from different drug categories have a firm place in a complex first-line therapy. Due to the large number of drugs available, it is necessary to identify the most effective therapies, whilst considering their side effects and impact on quality of life (QoL).

OBJECTIVES: To evaluate and compare the benefits and harms of first-line therapies for adults with advanced RCC, and to produce a clinically relevant ranking of therapies. Secondary objectives were to maintain the currency of the evidence by conducting continuous update searches, using a living systematic review approach, and to incorporate data from clinical study reports (CSRs).

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings and relevant trial registries up until 9 February 2022. We searched several data platforms to identify CSRs.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating at least one targeted therapy or immunotherapy for first-line treatment of adults with advanced RCC. We excluded trials evaluating only interleukin-2 versus interferon-alpha as well as trials with an adjuvant treatment setting. We also excluded trials with adults who received prior systemic anticancer therapy if more than 10% of participants were previously treated, or if data for untreated participants were not separately extractable.

DATA COLLECTION AND ANALYSIS: All necessary review steps (i.e. screening and study selection, data extraction, risk of bias and certainty assessments) were conducted independently by at least two review authors. Our outcomes were overall survival (OS), QoL, serious adverse events (SAEs), progression-free survival (PFS), adverse events (AEs), the number of participants who discontinued study treatment due to an AE, and the time to initiation of first subsequent therapy. Where possible, analyses were conducted for the different risk groups (favourable, intermediate, poor) according to the International Metastatic Renal-Cell Carcinoma Database Consortium Score (IMDC) or the Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Our main comparator was sunitinib (SUN). A hazard ratio (HR) or risk ratio (RR) lower than 1.0 is in favour of the experimental arm.

MAIN RESULTS: We included 36 RCTs and 15,177 participants (11,061 males and 4116 females). Risk of bias was predominantly judged as being ‘high’ or ‘some concerns’ across most trials and outcomes. This was mainly due to a lack of information about the randomisation process, the blinding of outcome assessors, and methods for outcome measurements and analyses. Additionally, study protocols and statistical analysis plans were rarely available. Here we present the results for our primary outcomes OS, QoL, and SAEs, and for all risk groups combined for contemporary treatments: pembrolizumab + axitinib (PEM+AXI), avelumab + axitinib (AVE+AXI), nivolumab + cabozantinib (NIV+CAB), lenvatinib + pembrolizumab (LEN+PEM), nivolumab + ipilimumab (NIV+IPI), CAB, and pazopanib (PAZ). Results per risk group and results for our secondary outcomes are reported in the summary of findings tables and in the full text of this review. The evidence on other treatments and comparisons can also be found in the full text. Overall survival (OS) Across risk groups, PEM+AXI (HR 0.73, 95% confidence interval (CI) 0.50 to 1.07, moderate certainty) and NIV+IPI (HR 0.69, 95% CI 0.69 to 1.00, moderate certainty) probably improve OS, compared to SUN, respectively. LEN+PEM may improve OS (HR 0.66, 95% CI 0.42 to 1.03, low certainty), compared to SUN. There is probably little or no difference in OS between PAZ and SUN (HR 0.91, 95% CI 0.64 to 1.32, moderate certainty), and we are uncertain whether CAB improves OS when compared to SUN (HR 0.84, 95% CI 0.43 to 1.64, very low certainty). The median survival is 28 months when treated with SUN. Survival may improve to 43 months with LEN+PEM, and probably improves to: 41 months with NIV+IPI, 39 months with PEM+AXI, and 31 months with PAZ. We are uncertain whether survival improves to 34 months with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. Quality of life (QoL) One RCT measured QoL using FACIT-F (score range 0 to 52; higher scores mean better QoL) and reported that the mean post-score was 9.00 points higher (9.86 lower to 27.86 higher, very low certainty) with PAZ than with SUN. Comparison data were not available for PEM+AXI, AVE+AXI, NIV+CAB, LEN+PEM, NIV+IPI, and CAB. Serious adverse events (SAEs) Across risk groups, PEM+AXI probably increases slightly the risk for SAEs (RR 1.29, 95% CI 0.90 to 1.85, moderate certainty) compared to SUN. LEN+PEM (RR 1.52, 95% CI 1.06 to 2.19, moderate certainty) and NIV+IPI (RR 1.40, 95% CI 1.00 to 1.97, moderate certainty) probably increase the risk for SAEs, compared to SUN, respectively. There is probably little or no difference in the risk for SAEs between PAZ and SUN (RR 0.99, 95% CI 0.75 to 1.31, moderate certainty). We are uncertain whether CAB reduces or increases the risk for SAEs (RR 0.92, 95% CI 0.60 to 1.43, very low certainty) when compared to SUN. People have a mean risk of 40% for experiencing SAEs when treated with SUN. The risk increases probably to: 61% with LEN+PEM, 57% with NIV+IPI, and 52% with PEM+AXI. It probably remains at 40% with PAZ. We are uncertain whether the risk reduces to 37% with CAB. Comparison data were not available for AVE+AXI and NIV+CAB.

AUTHORS’ CONCLUSIONS: Findings concerning the main treatments of interest comes from direct evidence of one trial only, thus results should be interpreted with caution. More trials are needed where these interventions and combinations are compared head-to-head, rather than just to SUN. Moreover, assessing the effect of immunotherapies and targeted therapies on different subgroups is essential and studies should focus on assessing and reporting relevant subgroup data. The evidence in this review mostly applies to advanced clear cell RCC.

PMID:37146227 | DOI:10.1002/14651858.CD013798.pub2

J Ultrasound Med. 2023 May 5. doi: 10.1002/jum.16252. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the role of superb microvascular imaging (SMI) and shear wave elastography (SWE) in the prediction of malignancy and invasiveness of isolated microcalcifications (MC) that can be visualized by ultrasonography (US).

MATERIAL AND METHODS: Sixty-seven women with MC, who were considered suspicious on mammography were evaluated. Only those lesions that could be visualized by US and presented as non-mass lesion were included. They were evaluated by B-mode US, SMI, and SWE before US-guided core-needle biopsy. B-mode US, SMI (vascular index (SMIvi)), and SWE (E-mean, E-ratio) findings were compared with histopathologic features.

RESULTS: Pathology confirmed 45 malignant (21 invasive and 24 in situ carcinomas) and 22 benign lesions. There was a statistically significant difference between malignant and benign groups in terms of size (P = .015), distortion (P = .028), cystic component (P < .001), E-mean (P < .001), E-ratio (P < .001), and SMIvi (P = .006). For differentiation of invasiveness E-mean (P = .002), E-ratio (P = .002), and SMIvi (P = .030) were statistically significant. According to ROC analysis E-mean (cut-off point at 38 kPa) was the most sensitive (78%) and the most specific (95%) value among four numeric parameters (size, SMI, E-mean, and E-ratio) with AUC = 0.895, PPV = 97%, and NPV = 68% in detecting malignancy. In the evaluation of invasiveness, the most sensitive (71.4%) method was SMI (cut-off point at 3.4) and the most specific (72%) method was E-mean (cut-off point at 91.5 kPa).

CONCLUSION: Our study shows that adding SWE and SMI to the sonographic evaluation of MC would be an advantage for US-guided biopsy. Including suspicious areas according to SMI and SWE in the sampling area can help target the invasive part of the lesion and avoid underestimation of core biopsy.

PMID:37146224 | DOI:10.1002/jum.16252

Chirurgia (Bucur). 2023 Apr;118(2):137-145. doi: 10.21614/chirurgia.2812.

ABSTRACT

Background: The nodules diagnosed as the “atypia of undetermined significance” category are a heterogenous group with an indeterminate risk of malignancy. This study aimed to perform a detailed cytological examination of the preparations to determine the cytomorphological criteria that may be useful to distinguish benign cases from malignant ones, correlate them with ultrasonographic findings, and compare them with the final pathological result in surgically treated patients. Methods: The preparations of patients classified as Bethesda 3 were re-evaluated; presence or absence of one of 11 parameters (hypochromasia, oval nucleus, colloid, intra-nuclear pseudoinclusions, nuclear grooving, nuclear moldering, isolated nuclear enlargement, nuclear irregularity, nuclear size, microfollicular pattern, distinct nucleoli) and correlating with surgical outcomes by adding ultrasonographic findings to statistically significant parameters. Results: Two hundred and six fine needle aspirations (FNA) procedures were classified as Bethesda 3. A total of 53 patients underwent surgery; 28 (52.8%) of them were benign, and 25 (47.1%) were malignant. Thirty-two (15.5%) accepted direct surgery; 53 patients underwent repeat FNA at 3-6 month intervals and those with malignancy and repeated Bethesda 3 interpretation were operated. One hundred twenty-one (69.5%) patients who did not undergo biopsy were invited for ultrasonographic controls at 3-6 month intervals. Among the 11 cytomorphologic parameters evaluated, 7 were found to be statistically significant (p 0.05) with malignancy. When at least 3 of these parameters were positive, the malignancy rate was 92%. Malignancy was present in 19 (61.3%) of the patients with high risk nodules (TIRADS = 4), compared to only 6 (35.8%) of the low-risk (TIRADS = 3); there was a significant correlation between the presence of malignancy and TIRADS score (p=0.015). The preparations that displayed nucleus atypia were closely associated with the ultrasonographically high-risk group. Conclusion: The parameters indicating nuclear atypia, presence of more than 3 cytomorphological factors, TIRADS score 4 were significantly associated with malignancy; nuclear atypia were closely associated with the ultrasonographically high TIRADS. No significant correlation was found between the presence of “microfollicular pattern” and malignancy.

PMID:37146190 | DOI:10.21614/chirurgia.2812

J Med Internet Res. 2023 Jan 26. doi: 10.2196/43965. Online ahead of print.

ABSTRACT

BACKGROUND: Telehealth has become widely utilized as a novel way to provide outpatient care during the coronavirus disease (COVID-19) pandemic, but data about telehealth use in primary care remains limited. Studies in other specialties raise concerns that telehealth may be widening existing healthcare disparities, requiring further scrutiny of trends in telehealth utilization.

OBJECTIVE: Our study aims to further characterize sociodemographic differences in primary care utilization via telehealth compared to in-person office visits before and during the COVID-19 pandemic, and determine if these disparities changed throughout 2020.

METHODS: We conducted a retrospective cohort study in a large U.S. academic center with 46 primary care practices from April-December 2019 and April-December 2020. Data were subdivided into calendar quarters and compared to determine evolving disparities throughout the year. We queried and compared billed outpatient encounters in General Internal Medicine and Family Medicine via binary logic mixed effects regression model and estimated odds ratios with 95% confidence intervals (OR, 95% CI). We used sex, race, and ethnicity of the patient attending each encounter as fixed effects. We analyzed socioeconomic status of patients in the institution’s primary county based on the zip code the patient was residing in.

RESULTS: A total of 81,822 encounters in the pre-COVID-19 timeframe and 47,994 encounters in the intra-COVID-19 timeframe were analyzed; in the intra-COVID-19 timeframe, a total of 5,322 (11.1%) were telehealth encounters. Patients living in zip codes with high supplemental nutritional assistance usage were less likely to utilize primary care in the intra-COVID-19 timeframe (OR 0.94, 95% CI 0.90-0.98, P= .006). Encounters with the following patients were less likely to be via telehealth compared to in-person office visits- patients who self-identified as Asian (OR 0.74, 95% CI 0.63-0.86) and Nepali (OR 0.37, 95% CI 0.19-0.72), patients insured by Medicare (OR 0.77, 95% CI 0.68-0.88), and patients living in zip codes with high supplemental nutritional assistance usage (OR 0.84, 95% CI 0.71-0.99). Many of these disparities persisted throughout the year. While there was no statistically significant difference in telehealth utilization for patients insured by Medicaid throughout the whole year, sub analysis of quarter 4 found encounters with patients insured by Medicaid were less likely to be via telehealth (OR 0.73, 95% CI 0.55-0.97, P=.03).

CONCLUSIONS: Telehealth was not utilized equally by all patients within primary care throughout the first year of the COVID-19 pandemic, specifically by patients who self-identified as Asian and Nepali, were insured by Medicare, and lived in zip codes with low socioeconomic status. As the COVID-19 pandemic and telehealth infrastructure change, it is critical we continue to reassess the utilization of telehealth. Institutions should continue to monitor disparities in telehealth access, and advocate for policy changes that may improve equity.

PMID:37146176 | DOI:10.2196/43965

Liver Transpl. 2023 May 8. doi: 10.1097/LVT.0000000000000169. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT.

METHODS: LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole room calorimetry and is expressed as respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state.

RESULTS: The clinical, metabolic and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (β-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (β-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (β-coefficient 0.447, p = 0.02) directly correlated with severity of weight gain. No statistically significant relationship between peak RQ, trough RQ and weight change was demonstrated.

CONCLUSION: Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity post-LT with potential to develop new diagnostics and therapeutics.

PMID:37146168 | DOI:10.1097/LVT.0000000000000169

Mol Pharm. 2023 May 5. doi: 10.1021/acs.molpharmaceut.3c00013. Online ahead of print.

ABSTRACT

Therapeutic proteins can be challenging to develop due to their complexity and the requirement of an acceptable formulation to ensure patient safety and efficacy. To date, there is no universal formulation development strategy that can identify optimal formulation conditions for all types of proteins in a fast and reliable manner. In this work, high-throughput characterization, employing a toolbox of five techniques, was performed on 14 structurally different proteins formulated in 6 different buffer conditions and in the presence of 4 different excipients. Multivariate data analysis and chemometrics were used to analyze the data in an unbiased way. First, observed changes in stability were primarily determined by the individual protein. Second, pH and ionic strength are the two most important factors determining the physical stability of proteins, where there exists a significant statistical interaction between protein and pH/ionic strength. Additionally, we developed prediction methods by partial least-squares regression. Colloidal stability indicators are important for prediction of real-time stability, while conformational stability indicators are important for prediction of stability under accelerated stress conditions at 40 °C. In order to predict real-time storage stability, protein-protein repulsion and the initial monomer fraction are the most important properties to monitor.

PMID:37146162 | DOI:10.1021/acs.molpharmaceut.3c00013