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Introduction: Monogenic diseases can be diagnosed before birth. Systemic fetal administration of nanoparticles (NPs) grants therapeutic access to developing stem cell populations impacted by these classes of disease. Delivery of editing reagents in these NPs administered before birth has yielded encouraging results in preclinical mouse models of monogenic diseases.

Methods: To translate this strategy clinically, the safety and efficacy of this strategy in larger animals will be necessary. We performed a pilot biodistribution study in 3 fetal nonhuman primates (NHPs) in mid-gestation examining systemic delivery of polymeric NPs loaded with fluorescent dye.

Results: We found several similarities in distribution to our experience in mice, namely, extensive uptake in fetal liver and spleen. A striking finding that is not recapitulated in the mouse was the accumulation of NPs in the zones of proliferation and ossification of the fetal bone. Of great importance, there did not appear to be NP accumulation in the fetal male or female germline zones or maternal tissue.

Conclusion: These studies were vital to the next step of testing editing reagents in the fetal NHP with a goal of treating monogenic diseases before birth.

Introduction: The factors influencing meconium aspiration syndrome (MAS) severity remain poorly understood. In a piglet model of MAS, we hypothesized the respiratory microbiome would reflect the bacterial signature of meconium with short-chain fatty acid (SCFA) accumulation as a byproduct of bacterial fermentation.

Methods: Cesarean section at approximately 115-day term was performed on two sows. Male (9) and female (3) piglets were delivered, instrumented, anesthetized, and randomized into a Control (n = 6) or MAS group (n = 6). MAS received a meconium slurry (3 mL/kg) aspiration injury. Experimental animals were monitored continuously, ventilated, and resuscitated for 24 h. BALF was collected for 16S microbiome sequencing and SCFA analysis by gas chromatography. Effects of SCFAs on A549 alveolar pulmonary epithelial in vitro cell viability and inflammation were assessed.

Results: The MAS group had significantly higher fluid and vasopressor requirements than the Control group (p < 0.05) though both groups developed lung injury. The meconium microbiome demonstrated a difference in genus proportions as compared with the BALF of the Control and MAS groups. The MAS group had a relative increase in propionic acid-forming bacteria and higher BALF concentrations of propionic acid (0.6 ± 0.2 mmol/kg) than the Control group (0.2 ± 0.2 mmol/kg; p > 0.05). Propionic acid was associated with decreased pulmonary epithelial cell viability and an upregulated pro-inflammatory response.

Conclusions: Meconium may host a microbiome with byproducts that interact with the pulmonary epithelium and influence lung injury severity in MAS.

Introduction: Transposition of the great arteries (TGA), especially with intact ventricular septum (TGA-IVS), presents unique challenges during fetal-to-neonatal transition, which can contribute to developing persistent pulmonary hypertension of the newborn (PPHN).

Case presentation: A male newborn with TGA-IVS, delivered via caesarean section, presented with hypoxemia and tachycardia immediately after birth (preductal SpO₂: 50-60%, post-ductal SpO₂: 70-75%). Echocardiography revealed a floppy interatrial septum and two interatrial connections with bidirectional shunting. Ductal flow showed systolic right-to-left shunting, suggesting high pulmonary vascular resistance. Immediate post-birth management included non-invasive respiratory support with continuous positive airway pressure at 100% oxygen and administration of prostaglandin E2 to maintain ductal patency. Despite initial low oxygen saturation levels, escalation of intensive treatments was deferred based on continuous trend monitoring of vital signs and echocardiographic indicators. Oxygenation and circulation gradually improved within the first 2 h after birth to normal values, obviating escalation of intensive interventions like intubation, nitric oxide and/or balloon atrial septostomy. Arterial switch operation at day 3 post-birth was successful.

Conclusion: This case highlights the possible contribution of fetal-to-neonatal transition in TGA-IVS to developing PPHN, which may subside after transition. Moreover, this case highlights the potential for providing a gentle hemodynamic transition without invariably needing early invasive interventions after birth.

Introduction: Peritonitis is a significant complication of peritoneal dialysis (PD). Additionally, in severe or prolonged cases of peritonitis, the structure and function of the peritoneum may change, making it difficult to continue PD. Thus, identifying the causative agent and early administration of antibiotics are essential to minimize the risk of treatment failure. Meanwhile, bacterial peritonitis caused by nontuberculous Mycobacteria (NTM) are difficult to identify. NTM are also among the most difficult organisms to eradicate. Oftentimes, removal of the peritoneal catheter and multiple antibiotics are required to eradicate NTM infections.

Case presentation: Herein, we report a case of peritonitis caused by Mycobacterium fortuitum in a 3-year-old boy undergoing PD. The patient had a history of an initial PD catheter exit site infection caused by M. fortuitum that led to PD-associated peritonitis. Consequently, the catheter was removed, and the patient was switched to hemodialysis and treated with multiple antibiotics.

Conclusion: This rare cause of peritonitis is associated with a high mortality and severe morbidity and usually requires removal of the PD catheter as well as prolonged treatment with multiple antibiotics. When there is NTM infection around the PD catheter, such as in an ulcer, it is necessary to remove the catheter and transition to a hemodialysis until the infection has healed.

Introduction: Knowing an individualized outcome prediction is essential when counseling patients before surgery. We aim to identify predictors and build a model for the outcome of radiofrequency uvulopalatopharyngoplasty with tonsillectomy (rfUPPP + TE).

Methods: All adult patients undergoing rfUPPP + TE for sleep-disordered breathing from 2015 to 2022 in our institution were included. Preoperative evaluations included detailed upper airway examinations and standardized questionnaires. Postoperative outcomes were measured through home sleep apnea testing and repeated questionnaires 3 months post-surgery. The primary endpoint was the postoperative apnea-hypopnea index (AHI) and the AHI responders using the Sher criteria.

Results: We analyzed 247 patients with a mean age of 46 ± 11 years, predominantly male (88.7%), and a mean BMI of 29.0 kg/m². The mean AHI was reduced from 26.4 ± 18.6/h preoperatively to 16.2 ± 14.6/h postoperatively. Daytime sleepiness improved from 8.9 ± 48 to 4.0 ± 3.1 and snoring from 7.9 ± 2.1 to 3.3 ± 2.2. Multivariate analysis indicated that higher tonsil grades, preoperative AHI, and snoring levels were associated with a greater reduction in AHI. Age and body weight were negative predictors for AHI reduction. For AHI responders, according to Sher, tonsil grade was the only predictor in a multivariate analysis. The ROC curve of this simple model, with a corrected AUC of 0.625, compared favorably against two established models.

Conclusion: Our study highlights that tonsil grade, preoperative AHI, snoring, and, to a smaller extent, age and weight are key determinants of AHI reduction, emphasizing the importance of preoperative evaluation. Despite the multifactorial nature of obstructive sleep apnea, preoperative evaluation can predict the outcome of rfUPPP + TE and guide surgical planning.

Introduction: Percutaneous microwave ablation (MWA) is clinically accepted for the treatment of lung tumors and oligometastatic disease. Bronchoscopic MWA is under development and evaluation in the clinical setting. We previously reported on the development of a bronchoscopy-guided MWA system integrated with clinical virtual bronchoscopy and navigation and demonstrated the feasibility of transbronchial MWA, using a maximum power of 60 W at the catheter input. Here, we assessed the performance of bronchoscopy-guided MWA with an improved catheter (maximum power handling of up to 120 W) in normal porcine lung in vivo (as in the previous study).

Methods: A total of 8 bronchoscopy-guided MWA were performed (n = 2 pigs; 4 ablations per pig) with power levels of 90 W and 120 W applied for 5 and 10 min, respectively. Virtual bronchoscopy planning and navigation guided transbronchial or endobronchial positioning of the MWA applicator for ablation of lung parenchyma. Following completion of ablations and post-procedure CT imaging, the lungs were harvested and sectioned for gross and histopathologic ablation analysis.

Results: Bronchoscopy-guided MWA with applied energy levels of 90 W/5 min and 120 W/10 min yielded ablation zones with short-axis diameters in the range of 20-28 mm (56-116% increase) as compared to ∼13 mm from our previous study (60 W/10 min). Histology of higher-power and previous lower-power ablations was consistent, including a central necrotic zone, a thermal fixation zone with intact tissue architecture, and a hemorrhagic periphery. Catheter positioning and its confirmation via intra-procedural 3D imaging (e.g., cone-beam CT) proved to be critical for ablation consistency.

Conclusion: Bronchoscopy-guided MWA with an improved catheter designed for maximum power 120 W yields large ablations in normal porcine lung in vivo.

Introduction: Stroke is characterized by high incidence, recurrence rate, and mortality. Patients with acute ischemic stroke (AIS) who are ineligible for acute revascularization therapy require more effective medication treatments. A previous clinical study showed that Ruyi Zhenbao tablets and Baimai ointments might be effective against AIS; however, high-quality clinical evidence supporting their application in AIS is lacking. To explore the efficacy of the two classic Tibetan medicines in the treatment of AIS, a randomized clinical trial will be conducted in patients with AIS who are not eligible for thrombolytic treatment.

Methods: A prospective, randomized, multiple-center, double-blinded, placebo-controlled, and parallel-group trial will be conducted. We shall randomize 480 eligible participants to either the intervention or the control group. The distribution ratio of each group will be 1:1:1:1, including 120 patients each in the dual-medication group, the Baimai ointment group, the Ruyi Zhenbao tablet group, and the placebo group. Participants will be treated with medication for 8 weeks, and they will receive three follow-up visits: at 4 weeks (D29), 8 weeks (D56), and 90 days (D90) after commencing treatment. The primary outcome will be D90 change in the simplified Fugl-Meyer score from baseline to posttreatment. The secondary outcomes are as follows: D29 change of simplified Fugl-Meyer score from baseline to posttreatment; proportion of participants whose D29 NIHSS scores decreased by four or more points from baseline D90 proportion of subjects with mRS score of 0-2 (inclusive); D90 proportion of subjects with Barthel index score ≥95; D90 incidence of cardiovascular and cerebrovascular events. Safety endpoint includes mortality within 90 days; proportion of subjects with adverse events/serious adverse events within 90 days.

Conclusion: This research protocol lays a solid groundwork for its practical execution. This study is poised to serve as a reference for other Tibetan medicine researchers, contributing to the reduction of stroke-related expenditures globally and, in turn, benefiting a broader population of stroke patients.

Introduction: Rectus sheath hematomas (RSHs) can occur from the rupture of the epigastric arteries, leading to blood accumulation within the rectus abdominis sheath. Herein, we report the unique case of an RSH resulting in acute ureteral obstruction, which was associated with the use of a handheld deep-tissue percussive massage device in attempts to relieve abdominal pain.

Case report: A morbidly obese man in his late 50s was admitted with complications of COVID-19, including acute respiratory syndrome, bilateral peroneal deep vein thromboses, and acute kidney injury. He was treated with anticoagulants (subcutaneous enoxaparin and apixaban), dexamethasone, and remdesivir. He developed severe abdominal pain, and a large (14 × 17 cm) right rectus sheath and an extraperitoneal pelvic hematoma were identified by computed tomography. The hematoma extended across the midline into the left pelvis and the retroperitoneum with associated mild right hydronephrosis. A handheld percussive massage device (Theragun^®) was applied repeatedly at the site of enoxaparin injection into the abdominal wall in attempts to alleviate the pain. On day 12, bilateral nephrostomy tubes were inserted. A nephrostogram revealed mild hydroureteronephrosis to the ureterovesicular junction bilaterally and extrinsic compression of the bladder. On day 17, the patient suffered a cardiac arrest and died.

Conclusion: This case report offers insights into the pathophysiology of obstructive uropathy and is a reminder of the importance of considering uncommon causes of obstructive uropathy in the diagnosis and management of AKI, particularly in hospitalized patients receiving anticoagulation. We know of no previous reference of obstructive uropathy caused by retroperitoneal hematoma associated with the use of a portable massage device applied to the abdominal wall.

Introduction: Magnetic resonance imaging (MRI) is a common procedure in tertiary care neonatal intensive care units (NICUs). MRIs aid in detailing structural anatomy and are increasingly utilized for prognostication. Keeping babies calm and motion-free in the MRI suite is challenging, and various approaches have been adopted to obtain the best image quality. We share our experience of intervention bundle for procedural sedation with the novel use of buccal midazolam in our NICU for babies undergoing MRI.

Methods: This single-center quality improvement project comprised two epochs. Epoch 1 from April 2018 to December 2020 provided baseline data regarding sedation use and helped identify causes for suboptimal images and the adverse event rate. Following the implementation of an interventional bundle comprising specific midazolam dose recommendations tailored to background risk factors and streamlining the procedural sedation process, similar comparative data were collected in epoch 2 (May 2021 to December 2022) after a washout period.

Results: Of 424 patients, 238 and 108 had MRI done under either procedural sedation protocol or feed and wrap technique in epoch 1 and 2, respectively. After excluding babies whose MRIs were performed under sedative infusions, 30 (13%) babies had adverse events in epoch 1, while only 8 (7%) events occurred in epoch 2. There was also a 37% improvement in the documentation of procedural sedation between the two epochs.

Conclusion: Procedural sedation with buccal midazolam under neonatologist supervision is safe, efficient, and effective in babies undergoing MRI in this single-center study. More extensive studies may be warranted to assess the suitability of this sedation modality for broader use.

Introduction: Older adults with dementia who are on multiple medications are more vulnerable to the use of potentially inappropriate medications (PIMs), which can significantly increase the risk of adverse events and drug-related problems. PIMs use is prevalent and varies among older adults with dementia or cognitive impairment (CI) attending memory clinics. However, the prevalence of PIMs, polypharmacy, and hyper-polypharmacy among older adults with dementia or CI who are attending memory clinics is not well understood. We will conduct a systematic review and meta-analyses to examine the overall estimate of the prevalence of the PIMs, polypharmacy, and hyper-polypharmacy use among older adults attending memory clinics, with dementia or CI. The secondary objective of this study will be to compile a list of commonly implicated PIMs and to investigate factors that may be associated with using PIMs in this population.

Methods: Ovid MEDLINE, Ovid Embase, Scopus, Cochrane library, EBSCOhost CINAHL, and Ovid International Pharmaceutical Abstracts (IPA) will be systematically searched by a researcher (R.S.) with the help of a librarian (C.C.). All databases will be searched from inception to May 05, 2023. Cross-sectional, cohort, randomized clinical trials, quasi-experimental, and case-control studies will be included if they assess PIM's use among older adults with dementia and/or CI. A step-by-step guide by Pai et al. [Natl Med J India. 2004;17(2):86-95] will be followed when conducting this systematic review (S.R.). The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist will be followed for reporting this SR.

Conclusion: The findings from this SR/MA will identify the pooled prevalence of PIMs, providing a more precise estimate of the true prevalence of the PIMs, polypharmacy, hyper-polypharmacy in older adults with dementia or CI who are attending memory clinics at primary, secondary, or tertiary healthcare settings by considering the results of multiple studies.