Annals of medicine最新文献

Objective: To explore the feasibility and efficacy of the modified technique of totally intracorporeal ileal conduit (IC) construction via vaginal approach following robot-assisted radical cystectomy (RARC) in females.

Methods: By comparing the perioperative outcomes of the modified technique with extracorporeal urinary diversion (ECUD), 31 females treated for bladder cancer with RARC and IC from May 2020 to December 2023 were retrospectively analyzed and divided into two groups: the ECUD group (10 patients) and the modified intracorporeal urinary diversion (MICUD group) (21 patients). The modified technique involved performing transvaginal natural orifice specimen extraction surgery (TV-NOSES) after RARC; followed by the transvaginal placement of an Endo-GIA stapler to manipulate the bowel for intracorporeal IC construction.

Results: Both groups' surgeries were successfully completed by the same surgeon and team. Patients in the MICUD group had shorter total operative time, lower postoperative pain scores, quicker recovery, and shorter hospital stays. The learning curve of the MICUD showed two phases: a learning phase (cases 1-7) and a proficiency phase (cases 8-21). The incidence of postoperative complications between the two groups was similar. The mean follow-up times were 29.3 months (ECUD group) and 22.6 months (MICUD group). In the MICUD group, there was one case of local tumor recurrence, two cases of distant metastasis, including one death from progression; in the ECUD group, one patient had distant metastasis and died from progression.

Conclusion: RARC with MICUD represents a safe, feasible and easy-to-learn minimally invasive surgical approach. Patients experience less trauma and faster recoveries.

Objective: We attempted to evaluate the immediate high-grade squamous intraepithelial lesion-cervical intraepithelial neoplasia grade 2/3 or worse (HSIL-CIN2+/3+, hereafter referred to as CIN2+/3+) risk of specific human papillomavirus (HPV) genotype and form the precise risk-based triage strategy for atypical squamous cells of undetermined significance (ASC-US) women.

Methods: The clinical data of ASC-US women who underwent HPV genotyping testing and colposcopy were retrospectively reviewed. The distribution and CIN2+/3+ risks of specific HPV genotype were assessed by three approaches. The risk-based triage strategy was further established, and its efficacy in detecting CIN2+/3+ was estimated.

Results: Totally, 5553 ASC-US women including 3648 HPV-positive and 1905 HPV-negative were analysed. CIN2+/3+ were 662/319 cases, including 639/306 HPV-positive and 23/13 HPV-negative women. HPV16, HPV52, HPV58 and HPV18 were always among the top 5 ranking genotypes, no matter in HPV-positive women or in HPV-positive CIN2+/3+ cases. HPV16 and HPV33 carried the highest risk, while HPV73 and 26 carried the least risk for CIN2+/3+. Based on the immediate CIN2+/3+ risk of specific HPV genotype, 18 HPVs were divided into three risk-stratified groups. Only women infected with HPVs included in group A were necessary for immediate colposcopy. Compared with conventional strategy, this new risk-based strategy not only had higher specificity (CIN2+: p = .00; CIN3+: p = .01) and positive predictive value (CIN2+: p = .00; CIN3+: p = .03) for detecting CIN2+/3+, but also needed fewer colposcopies to identify each CIN2+/3+.

Conclusions: A new triage strategy for ASC-US women was successfully constructed based on CIN2+/3+ risks of 14 high-risk and 4 intermediate-risk HPVs, which could significantly reduce unnecessary colposcopies.

Objective: The prognosis for severe asthma is poor, and the current treatment options are limited. The methyl-CpG binding domain protein 2 (MBD2) participates in neutrophil-mediated severe asthma through epigenetic regulation. Neutrophil extracellular traps (NETs) play a critical role in the pathogenesis of severe asthma. This study aims to detect if MBD2 can reduce NETs formation and the potential mechanism in severe asthma.

Methods: A severe asthma model was established in C57BL/6 wild-type mice exposure to house dust mite (HDM), ovalbumin (OVA), and lipopolysaccharide (LPS). Enzyme-linked immunosorbent assay was used to measure the concentrations of IL-4, IL-17A, and IFN-γ in lung tissues. Flow cytometry was employed to determine the percentages of Th2, Th17, and Treg cells in lung tissues. Quantitative real-time polymerase chain reaction was utilized to assess the mRNA expression levels of MBD2, JAK2, and PAD4. Western blotting and immunofluorescence were conducted to detect the protein of MBD2, JAK2, PAD4, and CitH3. HL-60 cells were differentiated into neutrophil-like cells by culturing in a medium containing dimethyl sulfoxide and then stimulated with LPS. KCC-07, Ruxolitinib, and Cl-amidine were used to inhibit the expressions of MBD2, JAK2, and PAD4, respectively.

Results: Severe asthma mice were characterized by pulmonary neutrophilic inflammation and increased formation of neutrophil extracellular traps (NETs). The expression of MBD2, JAK2, and PAD4 was elevated in severe asthma mice. Inhibiting the expression of MBD2, JAK2, and PAD4 reduced NETs formation and decreased airway inflammation scores, total cell counts and neutrophil counts in BALF, and percentage of Th2 and Th17 cell in lung tissues, whereas increasing Treg cell counts. In both severe asthma mice and HL-60-differentiated neutrophil-like cells in vitro, inhibiting MBD2 reduced the mRNA and protein expression of JAK2 and PAD4, and inhibiting JAK2 reduced the expression of PAD4 mRNA and protein.

Conclusion: MBD2 regulates PAD4 expression through the JAK2 signaling pathway to promote NETs formation in mice with severe asthma. Further bench-based and bedside-based studies targeting the MBD2, PAD4, and JAK2 signaling pathways will help open new avenues for drug development of severe asthma.

Background: This study was aimed to explore the global burden and trends of Clostridioides difficile infections (CDI) associated diseases.

Methods: Data for this study were obtained from the Global Burden of Disease Study 2021. The burden of CDI was assessed using the age-standardized rates of disability-adjusted life years (ASR-DALYs) and deaths (ASDRs). Trends in the burden of CDI were presented using average annual percentage changes (AAPCs).

Results: The ASR-DALYs for CDI increased from 1.83 (95% UI: 1.53-2.18) per 100,000 in 1990 to 3.46 (95% UI: 3.04-3.96) per 100,000 in 2021, with an AAPC of 2.03% (95% CI: 1.67-2.4%). The ASDRs for CDI rose from 0.10 (95% UI: 0.08-0.11) per 100,000 in 1990 to 0.19 (95% UI: 0.16-0.23) per 100,000 in 2021, with an AAPC of 2.26% (95% CI: 1.74-2.79%). In 2021, higher burdens of ASR-DALYs (10.7 per 100,000) and ASDRs (0.53 per 100,000) were observed in high socio-demographic index (SDI) areas, and among age group over 70 years (31.62/100,000 for ASR-DALYs and 2.45/100,000 for ASDRs). During the COVID-19 pandemic, the global ASR-DALYs and ASDRs slightly decreased. However, in regions with low SDI, low-middle and middle SDI, those rates slightly increased.

Conclusion: The global burden of CDI has significantly increased, particularly in regions with high SDI and among individuals aged 70 years and above. During the COVID-19 pandemic period from 2020 to 2021, the burden of CDI further increased in regions with low, low-middle, and middle SDI. These findings underscore the need for increased attention and intervention, especially in specific countries and populations.

Objectives: Develop risk-adapted conditional biopsy pathways utilizing MRI in combination with prostate-specific antigen (PSA) density (PSAD) and the ratio of free to total PSA (f/tPSA), respectively, to enhance the detection of clinically significant prostate cancer (csPCa) while minimizing 'negative' biopsies in low-risk patients.

Methods: The Prostate Imaging Reporting and Data System (PI-RADS) category, PSAD, f/tPSA and biopsy-pathology of 1018 patients were collected retrospectively. Subsequently, PSAD and f/tPSA were divided into four intervals, which were then combined with the MRI findings to construct two risk stratification matrix tables. Six biopsy decision pathways were established: three clinical pathways based solely on PSAD and f/tPSA, and three MRI-combined pathways incorporating both PI-RADS and PSA-derived indicators. The biopsy and clinically insignificant PCa (ciPCa) avoidance, csPCa detection rate, and 'negative' biopsies proportion were assessed. Decision curve analysis (DCA) was employed to evaluate the net benefit associated with each pathway.

Results: When reporting PI-RADS 1 - 2, PSAD ≥ 0.20 ng/ml/cm³ or f/tPSA ≤ 0.10 were found to be useful for patient stratification. When reporting PI-RADS 3, PSAD ≥ 0.10 - 0.15 ng/ml/cm³ and f/tPSA ≤ 0.16 - 0.25 were helpful in distinguishing the risk of csPCa. The three MRI-combined pathways showed higher csPCa detection rates (94% to 96%) than the three clinical pathways (85% to 91%); 'MRI + PSAD + f/tPSA' demonstrated a high csPCa detection rate of 94% while maintaining the maximum biopsy avoidance and lowest 'negative' biopsy proportion of 40% and 25%, respectively. The DCA showed significantly higher net benefits for three MRI-combined pathways compared to all clinical pathways.

Conclusions: The integration of MRI and PSA-derived indicators enables effective patient risk stratification, thereby providing valuable decision-making pathways to enhance the management of csPCa while minimizing 'negative' biopsies.

Introduction: Infertility has become a major global issue due to the trend of delaying marriage and advanced maternal age. Family/Birth cohort studies are essential for exploring ways to enhance health outcomes at both the individual and societal levels. However, there is a shortage of cohorts that include families who have utilized assisted reproductive technology (ART), particularly initiated at the early stages before pregnancy. The Assisted Reproductive Technology Cohort (APP-Cohort) is a prospective study aiming to investigate the epidemiology and risk factors of adverse gestational outcomes and other health issues in couples who have conceived through ART or naturally.

Methods: The cohort study's baseline survey commenced in January 2022 at several locations in Beijing, and enrollment is currently in progress. Both spouses filled out a questionnaire covering demographic, socio-economic, and various modifiable risk factors to gather information on their lifestyle. Physical examinations and biochemical tests were carried out, alongside regular yearly health check-ups throughout pregnancy and childhood. The survey data will be connected to electronic medical records to compile health information on the couples, newborns, and children.

Discussion: The APP-Cohort study collected data from both wives and husbands before conception, allowing for early assessment of environmental risk factors for maternal and offspring health. With a focus on various types of risk factors such as genetic, environmental, and shared familial traits, the ongoing follow-up of this study will enable researchers to evaluate and distinguish the impacts of these factors on pregnancy outcomes, perinatal health, and children's health for individuals conceived naturally versus those conceived through ART. By utilizing practical experience and advanced mathematical analysis of the extensive data, the APP-Cohort study will provide valuable insights to promote the administration and success rate of ART in China.

Background: Nurses on the frontlines of the pandemic have increased workloads, burnout, and virus exposure, leading to mental health challenges and a lack of resources for patient care. Mental health support for nurses during the COVID-19 outbreak has become a priority. This study evaluated psychological health outcomes of among nurses during the 2022-2023 COVID-19 pandemic in Taiwan, focusing on personal and work-related fatigue as key contributors to emotional distress.

Methods: A cross-sectional questionnaire was distributed to 200 nurses in a southern Taiwan hospital between 2022 and 2023. Emotional distress and mental health were assessed using the BSRS-5 (Brief Symptom Rating Scale) and CHQ-12 (Chinese Health Questionnaire). Correlation and regression analyses were conducted to identify factors influencing emotional distress and mental health outcomes.

Results: Nurses aged 40-59 (52.85, p = 0.01), those in emergency departments (56.71, p = 0.001), and those caring for COVID-19 patients (50, p = 0.007) reported higher personal exhaustion. Significant differences in work-related fatigue levels were observed based on working environments (52.78, p < 0.001), no beliefs regarding religion (46.53, p = 0.036), care for COVID-19 patients (47, p < 0.001) and previously diagnosed with COVID-19 (46.58, p = 0.005). Key factors influencing emotional distress included marital status, number of children, and workplace (p < 0.05), while mental health variations were noted  in age, marital status, number of children, workplace, and years of experience (p < 0.05). During the COVID-19 pandemic, nurses' emotional distress and mental health were significantly correlated with specific stressors such as age, workplace, care for confirmed COVID-19 patients, and previous COVID-19 diagnoses (p < 0.001).

Conclusions and implications for nursing management: This study highlights the stressors affecting nurses' mental health during the 2022-2023 COVID-19 pandemic, emphasizing the need for stress-specific mental health support. Understanding these stress-specific factors is important for figuring out what nurses need to improve their mental health, which can lead to better care for patients.

Background: Sepsis or septic shock is associated with severe morbidity and mortality in patients with acute liver failure (ALF). This study aimed to explore the potential prognostic value of common clinical indicators in patients with ALF, sepsis and with and without shock.

Patients and methods: The clinical, laboratory, and microbiological data of patients with ALF and sepsis or septic shock who were admitted to the intensive care unit from January 2014 to December 2019 were collected retrospectively. Clinical indicators, outcomes and the associations among them were analyzed and defined.

Results: Of 150 patients, 64 (42.7%) and 86 (57.3%) were divided into the shock and non-shock groups, respectively. Plasma procalcitonin (PCT), C-reactive protein (CRP), and creatinine (Cre) levels, aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio, and prothrombin time (PT) in the shock group and plasma PCT and Cre levels in the non-shock group were positively correlated with 30-day, 60-day, and 90-day mortality. Furthermore, plasma ALT levels were positively correlated with 60-day and 90-day mortality, and PTA showed negative correlations with 30-day, 60-day, and 90-day mortality in both groups. Multivariate logistic regression analysis revealed that the combination of plasma PCT and CRP levels, the combination of plasma PCT and ALT levels, and the combination of plasma ALT levels and PTA were found to be associated with 90-day mortality.

Conclusions: Clinical indicators, especially plasma PCT, CRP, and ALT levels, PTA, and their combinations were associated with poor outcomes in patients with ALF, sepsis and with and without shock.

Background: A novel uncapped mRNA platform was developed.

Methods: Five lipid nanoparticle (LNP)-encapsulated mRNA constructs were made to evaluate several aspects of our platform, including transfection efficiency and durability in vitro and in vivo and the activation of humoral and cellular immunity in several animal models. The constructs were eGFP-mRNA-LNP (for enhanced green fluorescence mRNA), Fluc-mRNA-LNP (for firefly luciferase mRNA), S^δT-mRNA-LNP (for Delta strain SARS-CoV-2 spike protein trimer mRNA), gD^ED-mRNA-LNP (for truncated glycoprotein D mRNA coding ectodomain from herpes simplex virus type 2 (HSV2)) and gD^FR-mRNA-LNP (for truncated HSV2 glycoprotein D mRNA coding amino acids 1-400).

Results: Quantifiable target protein expression was achieved in vitro and in vivo with eGFP- and Fluc-mRNA-LNP. S^δT-mRNA-LNP, gD^ED-mRNA-LNP and gD^FR-mRNA-LNP induced both humoral and cellular immune responses comparable to those obtained by previously reported capped mRNA-LNP constructs. Notably, S^δT-mRNA-LNP elicited neutralizing antibodies in hamsters against the Omicron and Delta strains. Additionally, gD^ED-mRNA-LNP and gD^FR-mRNA-LNP induced potent neutralizing antibodies in rabbits and mice. The mRNA constructs with uridine triphosphate (UTP) outperformed those with N1-methylpseudouridine triphosphate (N1mψTP) in the induction of antibodies via S^δT-mRNA-LNP.

Conclusions: Our uncapped, process-simplified and economical mRNA platform may have broad utility in vaccines and protein replacement drugs.KEY MESSAGESThe mRNA platform described in our paper uses internal ribosome entry site (IRES) (Rapid, Amplified, Capless and Economical, RACE; Register as BH-RACE platform) instead of caps and uridine triphosphate (UTP) instead of N1-methylpseudouridine triphosphate (N1mψTP) to synthesize mRNA.Through the self-developed packaging instrument and lipid nanoparticle (LNP) delivery system, mRNA can be expressed in cells more efficiently, quickly and economically.Particularly exciting is that potent neutralizing antibodies against Delta and Omicron real viruses were induced with the new coronavirus S protein mRNA vaccine from the BH-RACE platform.

Background: Occult lymph node metastasis of papillary thyroid carcinoma is common. However, whether undergoing prophylactic lateral lymph node dissections is still controversial. This cross-sectional study with large cohort of patients aims to investigate the clinical value of Delphian and pre-tracheal lymph node in predicting lateral lymph node metastasis of papillary thyroid carcinoma.

Materials and methods: A retrospective analysis was conducted on 865 papillary thyroid carcinoma patients with Delphian and pre-tracheal lymph node data who underwent thyroidectomy plus central and lateral lymph node dissection. Data on clinicopathological characteristics were collected. Subsequently, a predictive model was established based on the results of the univariate and multivariate analyses.

Results: The rates of Delphian and pre-tracheal lymph node metastasis and lateral lymph node metastasis were 54.7% and 39.1%, respectively. Having ≥ 3 or 1-2 Delphian and pre-tracheal lymph node metastasis dramatically increased the risk of lateral lymph node metastasis (OR = 8.5, 95% CI 5.3-13.4 and OR = 3.9, 95% CI 2.7-5.7, respectively). The upper tumour had a 3.7 times higher risk of lateral lymph node metastasis than other locations. Patients ≤ 42 years or tumour size >8 mm had a higher risk of lateral lymph node metastasis.

Conclusions: Delphian and pre-tracheal lymph node metastasis was associated positively with the risk of lateral lymph node metastasis. For patients without clinical lateral lymph node metastasis, the Delphian and pre-tracheal lymph node could be considered to harvest as the first step in a thyroidectomy to facilitate further conduct of the operation.