Category: Statistics

Int J Gynecol Cancer. 2023 Jul 31:ijgc-2023-004615. doi: 10.1136/ijgc-2023-004615. Online ahead of print.

ABSTRACT

Placenta accreta spectrum encompasses cases where the placenta is morbidly adherent to the myometrium. Placenta percreta, the most severe form of placenta accreta spectrum (grade 3E), occurs when the placenta invades through the myometrium and possibly into surrounding structures next to the uterine corpus. Maternal morbidity of placenta percreta is high, including severe maternal morbidity in 82.1% and mortality in 1.4% in the recent nationwide U.S. statistics. Although cesarean hysterectomy is commonly performed for patients with placenta accreta spectrum, conservative management is becoming more popular because of reduced morbidity in select cases. Treatment of grade 3E disease involving the urinary bladder, uterine cervix, or parametria is surgically complicated due to the location of the invasive placenta deep in the maternal pelvis. Cesarean hysterectomy in this setting has the potential for catastrophic hemorrhage and significant damage to surrounding organs. We propose a step-by-step schema to evaluate cases of grade 3E disease and determine whether immediate hysterectomy or conservative management, including planned delayed hysterectomy, is the most appropriate treatment option. The approach includes evaluation in the antenatal period with ultrasound and magnetic resonance imaging to determine suspicion for placenta previa percreta with surrounding organ involvement, planned cesarean delivery with a multidisciplinary team including experienced pelvic surgeons such as a gynecologic oncologist, intra-operative assessment including gross surgical field exposure and examination, cystoscopy, and consideration of careful intra-operative transvaginal ultrasound to determine the extent of placental invasion into surrounding organs. This evaluation helps decide the safety of primary cesarean hysterectomy. If safely resectable, additional considerations include intra-operative use of uterine artery embolization combined with tranexamic acid injection in cases at high risk for pelvic hemorrhage and uretinary stent placement. Availability of resuscitative endovascular balloon occlusion of the aorta is ideal. If safe resection is concerned, conservative management including planned delayed hysterectomy at around 4 weeks from cesarean delivery in stable patients is recommended.

PMID:37524496 | DOI:10.1136/ijgc-2023-004615

Genome Res. 2023 Jul 31:gr.277491.122. doi: 10.1101/gr.277491.122. Online ahead of print.

ABSTRACT

Accurately measuring biological age is crucial for improving healthcare for the elderly population. However, the complexity of aging biology poses challenges in how to robustly estimate aging and in how to interpret the biological significance of the traits used for estimation. Here we present SCALE, a statistical pipeline that quantifies biological aging in different tissues using explainable features learned from literature and single-cell transcriptomic data. Applying SCALE to the “Mouse Aging Cell Atlas” (Tabula Muris Senis) data, we identified tissue-level transcriptomic aging programs for over 20 murine tissues and created a multi-tissue resource of mouse quantitative aging-associated genes. We observe that SCALE correlates well with other age indicators, such as the accumulation of somatic mutations, and can distinguish subtle differences in aging even in cells of the same chronological age. We further compared SCALE with other transcriptomic and methylation ‘clocks’ in data of aging muscle stem cells, Alzheimer’s disease, and heterochronic parabiosis. Our results confirm that SCALE is more generalizable and reliable in assessing biological aging in aging-related diseases and rejuvenating interventions. Overall, SCALE represents a valuable advancement in our ability to measure aging accurately, robustly, and interpretably in single cells.

PMID:37524436 | DOI:10.1101/gr.277491.122

Thorax. 2023 Jul 31:thorax-2022-219925. doi: 10.1136/thorax-2022-219925. Online ahead of print.

ABSTRACT

INTRODUCTION: Readmission rates following hospital admission with community-acquired pneumonia (CAP) have increased in the UK over the past decade. The aim of this work was to describe the cohort of patients with emergency 30-day readmission following hospitalisation for CAP in England and explore the reasons for this.

METHODS: A retrospective analysis of cases from the British Thoracic Society national adult CAP audit admitted to hospitals in England with CAP between 1 December 2018 and 31 January 2019 was performed. Cases were linked with corresponding patient level data from Hospital Episode statistics, providing data on the primary diagnosis treated during readmission and mortality. Analyses were performed describing the cohort of patients readmitted within 30 days, reasons for readmission and comparing those readmitted and primarily treated for pneumonia with other diagnoses.

RESULTS: Of 8136 cases who survived an index admission with CAP, 1304 (15.7%) were readmitted as an emergency within 30 days of discharge. The main problems treated on readmission were pneumonia in 516 (39.6%) patients and other respiratory disorders in 284 (21.8%). Readmission with pneumonia compared with all other diagnoses was associated with significant inpatient mortality (15.9% vs 6.5%; aOR 2.76, 95% CI 1.86 to 4.09, p<0.001). A diagnosis of hospital-acquired infection was more frequent in readmissions treated for pneumonia than other diagnoses (22.1% vs 3.9%, p<0.001).

CONCLUSION: Pneumonia is the most common condition treated on readmission following hospitalisation with CAP and carries a higher mortality than both the index admission or readmission due to other diagnoses. Strategies to reduce readmissions due to pneumonia are required.

PMID:37524392 | DOI:10.1136/thorax-2022-219925

Annu Rev Pharmacol Toxicol. 2023 Jul 31. doi: 10.1146/annurev-pharmtox-022823-113946. Online ahead of print.

ABSTRACT

Here we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-Ras^G12C. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-Ras^G12C with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding growth of insensitive cell clones, and proliferation. Statistics confirm the expectation that most resistance-related mutations are in cis, pointing to the high probability of cooperative, same-allele effects. In addition to targeted Ras inhibitors and drug combinations, bifunctional molecules and innovative tri-complex inhibitors to target Ras mutants are also under development. Since the identities and potential contributions of preexisting and evolving mutations are unknown, selecting a pharmacologic combination is taxing. Collectively, our broad review outlines considerations and provides new insights to pharmacology and resistance. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:37524384 | DOI:10.1146/annurev-pharmtox-022823-113946

J Periodontal Implant Sci. 2023 Jun 27. doi: 10.5051/jpis.2204320216. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to investigate the relationships between gingival thickness (GT) and keratinized gingiva width (KGW), papilla height (PH), and crown ratio (CR) by employing transgingival probing and an intraoral scanner (IOS).

METHODS: This cross-sectional study examined 360 maxillary anterior teeth from 60 patients. GT was assessed using transgingival probing with an endodontic spreader. KGW, CR, and PH were measured using an IOS. One-way analysis of variance, the Student’s t-test, and Spearman correlation coefficients were employed for statistical analysis.

RESULTS: Higher GT was significantly associated with thinner KGW in the central region (P=0.019). There was no statistically significant difference in GT between teeth (P=0.06). PH was lower in lateral teeth than in canines (P=0.047), with a PH of 2.99 mm in lateral teeth. The KGW was narrower in canines than in central teeth (P=0.007). A moderate correlation was observed between KGW and PH in the central region (P=0.01), while a weak negative correlation was found between KGW and CR (P=0.043).

CONCLUSIONS: A moderate negative correlation was found between GT and KGW, as well as between PH and KGW in central teeth. In contrast, a weak negative correlation existed between CR and KGW. The PH (2.99 mm) was lower in lateral teeth than in canines. The traditional paradigm, which suggests a positive correlation between KGW and GT, was re-evaluated by measuring KGW using an IOS.

PMID:37524382 | DOI:10.5051/jpis.2204320216

J Periodontal Implant Sci. 2023 Jun 12. doi: 10.5051/jpis.2204360218. Online ahead of print.

ABSTRACT

PURPOSE: The inflammatory response due to inflammatory cytokines, bacterial pathogens, and the altered lipoprotein metabolism in patients with periodontitis indicates that infection with periodontal anaerobic bacteria may influence atherogenesis in vitro and in vivo. We aimed to explore the effect of periodontitis concerning clinical and ultrasound markers of early atherosclerosis.

METHODS: In this case-control study, a total of 30 systemically healthy adults (15 with periodontitis and 15 without periodontitis) over 40 years of age were studied. Periodontitis was determined by measuring the clinical attachment level (CAL) and radiographic bone loss (RBL). Conventional cardiovascular risk factors, including body mass index, serum levels of total cholesterol (TCH), triglycerides (TG), and high-density and low-density lipoprotein (HDL and LDL, respectively) cholesterol were evaluated. Carotid artery intima-media thickness (IMT) was measured using ultrasonography.

RESULTS: The mean values of the CAL and carotid IMT were 5.02±0.9 mm and 0.084±0.01 cm vs. 1.6±0.61 mm and 0.072±0.02 cm in the periodontitis and healthy groups, respectively, reflecting statistically significant differences (P=0.001 and P=0.037, respectively). There were statistically significant differences in the serum levels of TCH, TG, and LDL between the 2 groups (P=0.017). The CAL and RBL were positively associated with carotid IMT and serum cholesterol levels, except for HDL, whereas tooth loss was not associated with any markers (P<0.05). Compared to the healthy group, participants with periodontitis exhibited 2.09 times higher odds (95% confidence interval, 1.22-3.59) of having subclinical atherosclerosis.

CONCLUSIONS: The presence of periodontitis increased the risk of atherosclerosis.

PMID:37524377 | DOI:10.5051/jpis.2204360218

J Am Vet Med Assoc. 2023 Jul 31:1-8. doi: 10.2460/javma.23.05.0288. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe radiotherapy outcomes for canine infiltrative lipomas and provide detailed radiotherapy planning data.

ANIMALS: 24 dogs from 2000 to 2020.

METHODS: In this retrospective study, dogs received 1 to 3 surgeries prior to conventionally fractionated radiotherapy for gross (18) or microscopic (8) infiltrative lipomas. Dogs received 45 to 51 Gray (Gy) in 15 to 20 daily fractions, with 71% of dogs receiving 48 Gy in daily 3-Gy fractions.

RESULTS: Masses were regionally located as follows: limbs (7), trunk (13), head/neck (4). At analysis, 16/24 dogs were deceased, 5/24 were alive (median follow-up for alive dogs: 1,216 days [range, 741 to 1,870 days]), and 3/24 were lost to follow-up. One living dog had progressive disease 923 days after completing conventionally fractionated radiotherapy and received another surgery. The estimated median overall survival (OS) after completing radiotherapy was 4.8 years (1,760 days; 95% CI, 1,215 to 2,777 days; range, 23 to 3,499 days) for any cause of death, and no patients were reported to have been euthanized or died from their tumor. No statistically significant difference was found for dogs based on gross versus microscopic disease (gross OS, 4.8 years vs microscopic OS, 3.6 years; P = .45). Furthermore, the number of surgeries before radiotherapy did not impact survival (P = .96). The survival difference between females (median OS, 7.6 years; 95% CI, 963 days to not reached) versus males (median OS, 4.6 years; 95% CI, 335 to 2,245 days; P = .05) was statistically significant, although 4/5 living dogs were female.

CLINICAL RELEVANCE: This study demonstrates lengthy survivals with radiotherapy, even with gross disease, for dogs with infiltrative lipomas.

PMID:37524353 | DOI:10.2460/javma.23.05.0288

Bone Joint J. 2023 Aug 1;105-B(8):920-927. doi: 10.1302/0301-620X.105B8.BJJ-2022-1104.R2.

ABSTRACT

AIMS: Traumatic central cord syndrome (CCS) typically follows a hyperextension injury and results in motor impairment affecting the upper limbs more than the lower, with occasional sensory impairment and urinary retention. Current evidence on mortality and long-term outcomes is limited. The primary aim of this study was to assess the five-year mortality of CCS, and to determine any difference in mortality between management groups or age.

METHODS: Patients aged ≥ 18 years with a traumatic CCS between January 2012 and December 2017 in Wales were identified. Patient demographics and data about injury, management, and outcome were collected. Statistical analysis was performed to assess mortality and between-group differences.

RESULTS: A total of 65 patients were identified (66.2% male (n = 43), mean age 63.9 years (SD 15.9)). At a minimum of five years’ follow-up, 32.3% of CCS patients (n = 21) had died, of whom six (9.2%) had died within 31 days of their injury. Overall, 69.2% of patients (n = 45) had been managed conservatively. There was no significant difference in age between conservatively and surgically managed patients (p = 0.062). Kaplan-Meier analysis revealed no significant difference in mortality between patients managed conservatively and those managed surgically (p = 0.819). However, there was a significant difference in mortality between the different age groups (< 50 years vs 50 to 70 years vs > 70 years; p = 0.001). At five years’ follow-up, 55.6% of the patient group aged > 70 years at time of injury had died (n = 15). Respiratory failure was the most common cause of death (n = 9; 42.9%).

CONCLUSION: Almost one-third of patients with a traumatic CCS in Wales had died within five years of their injury. The type of management did not significantly affect mortality but their age at the time of injury did. Further work to assess the long-term functional outcomes of surviving patients is needed to generate more reliable prognostic information.

PMID:37524347 | DOI:10.1302/0301-620X.105B8.BJJ-2022-1104.R2

Neuro Endocrinol Lett. 2023 Jul 28;44(5):283-289. Online ahead of print.

ABSTRACT

BACKGROUND: Cognitive impairment (CI) may be present in people with multiple sclerosis (PwMS) in different stages of the disease, as well as in PwMS with various degrees of disability. This study aimed to investigate cognitive decline over a period of 12 months and to examine an association between cognition and the disability in PwMS, also over a period of 12 months.

METHODS: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used, containing the Symbol Digit Modalities Test (SDMT), the Categorical Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test-Revised (BVMT-R). The Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9-HPT) were used to assess the degree of disability. For the analysis of cognitive decline over the period of 12 months, Wilcoxon signed-rank test (paired sample t-test) was used. For the correlation between cognition and disability, Spearman’s correlation test was used.

RESULTS: We observed statistically meaningful difference only in one measure of cognition (CVLT), not the other two (SDMT and BVMT-R). SDMT significantly correlated with methods assessing the degree of disability in both time points. In the second examination, we observed a correlation between BICAMS and 9-HPT. Similarly, SDMT and BVMT-R also correlated with EDSS.

CONCLUSION: To investigate the cognitive decline in PwMS, a longer period of time probably should have been chosen. EDSS is commonly used to monitor disease progression, but it does not include the evaluation of various parameters, such as cognition or upper limb function. Its use with the 9-HPT and cognitive tests may represent a more reliable and comprehensive assessment of a patient’s clinical condition.

PMID:37524317

Gynecol Endocrinol. 2023 Dec;39(1):2239934. doi: 10.1080/09513590.2023.2239934.

ABSTRACT

OBJECTIVE: Though recent studies have pointed out different manifestations between obese and nonobese patients with polycystic ovarian syndrome (PCOS), there is no clear evidence to confirm this viewpoint. Therefore, the metabolic characteristics of obese and nonobese patients with PCOS were systematically compared through meta-analysis in this study.

METHODS: Data were searched from PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wanfang databases. Articles on obese and nonobese patients with PCOS published from database inception to January 2022 were included. Meta-analysis was performed using Stata 16.0 statistical software.

RESULTS: A total of 739 articles were initially retrieved, and ultimately 14 studies were involved in the meta-analysis. Specifically, there were 801 patients in the observation group (obese patients with PCOS) and 925 patients in the control group (nonobese patients with PCOS). Compared with the control group, the observation group had significantly lower levels of sex hormone-binding globulin (SHBG), high-density lipoprotein (HDL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and higher levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL). Nevertheless, there were no significant differences between the two groups in systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, and testosterone.

CONCLUSION: Compared with nonobese patients with PCOS, obese patients with PCOS have worse blood lipid parameters and lower levels of LH and FSH. Also, there are significant differences in metabolic characteristics between the two groups of patients. Most importantly, our findings provide guidance for the clinical diagnosis and treatment of PCOS.

PMID:37524309 | DOI:10.1080/09513590.2023.2239934