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1.
Proc Natl Acad Sci U S A ; 121(27): e2314702121, 2024 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-38916997

RESUMEN

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD). KATNAL2, a member of Katanin family microtubule-severing ATPases, is a known ASD risk gene, but its roles in human brain development remain unclear. Here, we show that nonsense truncation of Katnal2 (Katnal2Δ17) in mice results in classic ciliopathy phenotypes, including impaired spermatogenesis and cerebral ventriculomegaly. In both humans and mice, KATNAL2 is highly expressed in ciliated radial glia of the fetal ventricular-subventricular zone as well as in their postnatal ependymal and neuronal progeny. The ventriculomegaly observed in Katnal2Δ17 mice is associated with disrupted primary cilia and ependymal planar cell polarity that results in impaired cilia-generated CSF flow. Further, prefrontal pyramidal neurons in ventriculomegalic Katnal2Δ17 mice exhibit decreased excitatory drive and reduced high-frequency firing. Consistent with these findings in mice, we identified rare, damaging heterozygous germline variants in KATNAL2 in five unrelated patients with neurosurgically treated CH and comorbid ASD or other neurodevelopmental disorders. Mice engineered with the orthologous ASD-associated KATNAL2 F244L missense variant recapitulated the ventriculomegaly found in human patients. Together, these data suggest KATNAL2 pathogenic variants alter intraventricular CSF homeostasis and parenchymal neuronal connectivity by disrupting microtubule dynamics in fetal radial glia and their postnatal ependymal and neuronal descendants. The results identify a molecular mechanism underlying the development of ventriculomegaly in a genetic subset of patients with ASD and may explain persistence of neurodevelopmental phenotypes in some patients with CH despite neurosurgical CSF shunting.


Asunto(s)
Cilios , Hidrocefalia , Microtúbulos , Animales , Hidrocefalia/genética , Hidrocefalia/patología , Hidrocefalia/metabolismo , Humanos , Ratones , Microtúbulos/metabolismo , Masculino , Cilios/metabolismo , Cilios/patología , Femenino , Katanina/metabolismo , Katanina/genética , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/metabolismo , Neuronas/metabolismo , Epéndimo/metabolismo , Epéndimo/patología , ATPasas Asociadas con Actividades Celulares Diversas/genética , ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Células Piramidales/metabolismo , Células Piramidales/patología
2.
Brain ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38889248

RESUMEN

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally-directed cognition. The present study employs stereo-electroencephalography in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by a stronger increase in gamma band power (30-70 Hz) coupled with lower theta band power (4-8 Hz). The difference in activity between the two networks was especially strong during the mind wandering task. Within the DMN, we found that the tasks showed different dynamics, with the alternate uses task engaging the DMN more during the initial stage of the task, and mind wandering in the later stage. Gamma power changes were mainly driven by lateral DMN sites, while theta power displayed task-specific effects. During alternate uses task, theta changes did not show spatial differences within the DMN, while mind wandering was associated to an early lateral and late dorsomedial DMN engagement. Furthermore, causal manipulations of DMN regions using direct cortical stimulation preferentially decreased the originality of responses in the alternative uses task, without affecting fluency or mind wandering. Our results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in divergent thinking. These findings shed light on the neural constructs supporting different forms of cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.

3.
J Hand Surg Am ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703146

RESUMEN

PURPOSE: Multiple procedures have been described for wrist and finger flexion contractures and spasticity. Fractional lengthening of forearm flexor tendons involves making parallel transverse tenotomies at the musculotendinous junction to elongate the muscle. Currently, there is limited literature to define the biomechanical consequences of this lengthening technique. METHODS: Forty-eight flexor tendons were harvested from eight paired upper limbs including flexor carpi radialis, flexor carpi ulnaris, flexor pollicis longus, and flexor digitorum superficialis tendons. Each tendon that was lengthened was paired with the contralateral tendon as a control. A pair of transverse tenotomies were completed for the fractional lengthening. The first tenotomy was performed at the musculotendinous junction where the tendon narrowed to 75% of its maximal width. The second tenotomy was made 1 cm distal to the first. Tendon length was measured before and after fractional lengthening at a constant resting tension of 1 N. The maximum load at failure of each tendon and the mechanism of failure were each measured and compared with the contralateral side. RESULTS: After fractional lengthening, the mean increase in resting tendon length was 4 mm. When loaded to failure, the mean maximum load of fractionally lengthened tendons was 42% of the mean maximum load of intact tendons. All lengthened tendons failed at the distal tenotomy site. CONCLUSIONS: Fractional lengthening resulted in an increase of 3-6 mm (mean: 4 mm) in tendon length at resting tension. There was a significant loss in tensile strength and load to failure following fractional lengthening compared with an intact musculotendinous unit. CLINICAL RELEVANCE: The reduction in tensile strength following fractional lengthening results in loads at failure that are, in some cases, lower than the estimated forces required to perform basic tasks. Caution during the healing and rehabilitation period is warranted.

4.
Cureus ; 16(3): e56334, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38628999

RESUMEN

INTRODUCTION: With innovations in transplant medicine and longer life expectancies in solid organ transplant (SOT) recipients, the incidence of shoulder arthroplasty is predictably rising in this population. Reverse shoulder arthroplasty (RSA) has become increasingly popular due to advances in prosthetic design with expanded indications. While previous studies have examined shoulder arthroplasty in SOT patients, information specifically related to RSA patients is largely unexplored. We aim to analyze the demographics and characteristics of SOT patients who have undergone RSA while assessing inpatient complication rates, length of stay (LOS), and hospital costs in these patients compared to a matched cohort of non-transplant patients. METHODS: The National Inpatient Sample (NIS) Database was utilized to identify all patients undergoing RSA from 2016 to 2019. We generated propensity-matched groups based on pre-operative variables (diabetes, tobacco use, sex, age, and obesity) to compare complications, LOS, and inpatient costs between the SOT and control groups. T-tests and Chi-squared tests were performed where appropriate and odds ratios were calculated. RESULTS: We identified 59925 patients who underwent RSA. Among those, 59769 patients (99.7%) did not have a SOT and 156 patients (0.26%) had a history of SOT. Patients in the SOT group were younger than the control group (67.0 versus 71.4 years, p<0.001). The SOT group were more likely males compared to the control group (53.8% versus 39.3%, p<0.001). Following 1:1 matching, there were 156 patients in each group. The SOT group had a higher risk of acute renal failure (ARF) compared to the control group (OR 9.41, 95% CI (2.13-41.49), p<0.001). The LOS (p<0.001) and inpatient costs (p<0.001) were higher in the SOT group. CONCLUSION: For RSA, SOT patients are younger and more likely male compared to those without SOT. Inpatient medical and surgical complications are similar between SOT and non-SOT patients, except SOT patients have a higher risk of ARF. SOT patients tend to have longer LOS and higher inpatient costs than non-SOT patients.

5.
J Gynecol Oncol ; 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38330380

RESUMEN

BACKGROUND: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, well-planned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. METHODS: The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m²), 4-6 times administered intravenously. The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05421650; Clinical Research Information Service Identifier: KCT0007137.

6.
J Hand Surg Am ; 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38416093

RESUMEN

PURPOSE: Proximal interphalangeal (PIP) joint arthrodesis is a procedure employed to address arthritis, instability, and deformity. Multiple fixation methods are available to maintain stability across the arthrodesis interval, including headless compression screws (HCSs), tension band wiring (TBW), plating, and Kirschner wire constructs. The purpose of this study was to compare the biomechanical properties of the HCS and TBW techniques. METHODS: Thirty-two nonthumb digits from the paired upper limbs of four fresh frozen cadavers were divided into pairs, matching contralateral digits from the same specimen. One PIP joint of each pair was fused with an antegrade 3.5 mm HCS, and the second was fused with TBW using 0.035 in. Kirschner wires with 24-gauge dental wire. Each construct was then stressed to 10 N in the radial deviation, ulnar deviation, flexion, and extension planes, and stiffness (N/mm) was calculated. The fingers were stressed to failure in extension with the ultimate load and mode of failure recorded. RESULTS: When stressed in extension, the HCS construct had a significantly greater mean stiffness than the TBW construct (16.4 N/mm vs 10.8 N/mm). The stiffness in all other planes of motion were similar between the two constructs. The mean ultimate load to failure in extension was 91.4 N for the HCS and 41.9 N for the TBW. The most common mode of failure was fracture of the dorsal lip of the proximal phalanx (13/16) for the HCS and bending of the K-wires (15/16) for TBW. CONCLUSIONS: Arthrodesis of the PIP joint using a HCS resulted in a construct that was significantly stiffer in extension with greater than double the load to failure compared to TBW. CLINICAL RELEVANCE: Although the stiffness required to achieve successful PIP joint arthrodesis has not been well quantified, the HCS proved to be the most favorable construct with respect to initial strength and stability.

7.
JTCVS Tech ; 23: 52-62, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38352019

RESUMEN

Objectives: To evaluate the safety and efficacy of the port access approach for left atrial (LA) myxoma resection and to analyze the learning curve for this procedure. Methods: Thirty-six consecutive patients with LA myxoma who underwent port access surgery between April 2018 and March 2023 were enrolled in this retrospective study. The procedure included (1) unilateral or bilateral femoral artery cannulation; (2) the use of three 5-mm trocars and a 20- to 30-mm port; (3) a transseptal, biatrial, or LA approach depending on the location of the tumor base; and (4) complete or subendocardial tumor resection. CUSUM analysis was used to evaluate the aortic cross-clamp (ACC) time and cardiopulmonary bypass (CPB) time learning curves. Variables among the learning curve phases were compared. Results: The average ACC and CPB times were 49 (range, 45-79) minutes and 127 (range, 120-164) minutes, respectively. There was 1 case of conversion to sternotomy due to aortic root bleeding and 1 case of unilateral pulmonary edema. CUSUMACCtime analysis included 3 phases: phase I, the initial learning period (cases 1-11); phase II, the technical competence period (cases 12-23); and phase III, the challenging period (cases 24-36). Conclusions: The port access approach is safe and feasible for LA myxoma resection. According to the learning curve analysis, 11 cases are required to achieve technical competence, and 23 cases are required to address highly challenging cases.

8.
Brain Stimul ; 16(6): 1792-1798, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38135358

RESUMEN

BACKGROUND: Deep brain stimulation (DBS) and other neuromodulatory techniques are being increasingly utilized to treat refractory neurologic and psychiatric disorders. OBJECTIVE: /Hypothesis: To better understand the circuit-level pathophysiology of treatment-resistant depression (TRD) and treat the network-level dysfunction inherent to this challenging disorder, we adopted an approach of inpatient intracranial monitoring borrowed from the epilepsy surgery field. METHODS: We implanted 3 patients with 4 DBS leads (bilateral pair in both the ventral capsule/ventral striatum and subcallosal cingulate) and 10 stereo-electroencephalography (sEEG) electrodes targeting depression-relevant network regions. For surgical planning, we used an interactive, holographic visualization platform to appreciate the 3D anatomy and connectivity. In the initial surgery, we placed the DBS leads and sEEG electrodes using robotic stereotaxy. Subjects were then admitted to an inpatient monitoring unit for depression-specific neurophysiological assessments. Following these investigations, subjects returned to the OR to remove the sEEG electrodes and internalize the DBS leads to implanted pulse generators. RESULTS: Intraoperative testing revealed positive valence responses in all 3 subjects that helped verify targeting. Given the importance of the network-based hypotheses we were testing, we required accurate adherence to the surgical plan (to engage DBS and sEEG targets) and stability of DBS lead rotational position (to ensure that stimulation field estimates of the directional leads used during inpatient monitoring were relevant chronically), both of which we confirmed (mean radial error 1.2±0.9 mm; mean rotation 3.6±2.6°). CONCLUSION: This novel hybrid sEEG-DBS approach allows detailed study of the neurophysiological substrates of complex neuropsychiatric disorders.


Asunto(s)
Estimulación Encefálica Profunda , Trastorno Depresivo Resistente al Tratamiento , Epilepsia , Humanos , Epilepsia/terapia , Electroencefalografía/métodos , Trastorno Depresivo Resistente al Tratamiento/terapia , Electrodos , Estimulación Encefálica Profunda/métodos , Electrodos Implantados
9.
J Neurooncol ; 165(2): 353-360, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37945818

RESUMEN

INTRODUCTION: Diffuse midline glioma (DMG) of the pons occurs in pediatric patients and carries a dismal prognosis. Biopsy is not necessary for diagnosis but provides information, particularly H3K27M status, with prognostic implications. Additionally, biopsy information may open therapeutic options such as clinical trials that require mutation status. Therefore, we sought to assess the safety of surgical biopsy in DMG patients as well as its potential impact on clinical course. METHODS: Retrospective analysis of patients who were radiographically and clinically diagnosed with pontine DMG in the last 5 years was performed. We assessed demographic, clinical, radiographic, surgical, and follow-up data. RESULTS: 25 patients were included; 18 (72%) underwent biopsy while 7 (28%) declined. 12 biopsies (67%) were performed with robotic arm and 5 (27%) with frameless stereotaxy. Three biopsied patients (17%) experienced new post-operative neurologic deficits (1 facial palsy, 1 VI nerve palsy and 1 ataxia) that all resolved at 2-week follow-up. All biopsies yielded diagnostic tissue. Fourteen patients (78%) had H3K27M mutation. Median OS for H3K27M patients was 10 months compared to 11 months in the wild-type patients (p = 0.30, log-rank test). Median OS for patients enrolled in clinical trials was 12 months compared to 8 months for non-trial patients (p = 0.076). CONCLUSION: In our series, stereotactic pontine DMG biopsies did not carry any permanent deficit or complication and yielded diagnostic tissue in all patients. Similar post-operative course was observed in both robot-assisted and frameless stereotactic approaches. There was no significant difference in survival based on mutation status or clinical trial enrollment.


Asunto(s)
Neoplasias Encefálicas , Glioma , Niño , Humanos , Biopsia , Neoplasias Encefálicas/patología , Glioma/genética , Glioma/cirugía , Glioma/diagnóstico , Mutación , Puente/patología , Puente/cirugía , Estudios Retrospectivos
10.
Innovations (Phila) ; 18(6): 574-582, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37997659

RESUMEN

OBJECTIVE: To evaluate the safety and efficacy of the Hanoi ASD procedure, which is totally endoscopic surgery for atrial septal defect (ASD) repair on beating heart. In addition, the present study also aimed to analyze the learning curve for this procedure. METHODS: From May 2016 to February 2023, 198 consecutive ASD patients weighing ≥20 kg were enrolled in the retrospective study. The Hanoi ASD procedure includes (1) unilateral or bilateral femoral arterial cannulation; (2) two or three 5 mm trocars and a 15 mm port; (3) ASD repair on beating heart, preventing air embolism with CO2 insufflation and keeping the left atrium full of blood; and (4) not snaring the inferior vena cava. Cumulative sum (CUSUM) analysis was used to evaluate the cardiopulmonary bypass (CPB) and operation time learning curves. Variables among the learning curve phases were compared. RESULTS: The CPB and operation times were 90 (72 to 115) min and 180 (150 to 220) min, respectively. Total drainage volume was 190 (120 to 290) mL. No endoscopic failure or major complications were complications were excluding factors causing bias, the CUSUMCPBtime analysis for the remaining 131 patients included 3 phases. Phase 1 was the initial learning period (cases 1 to 34), phase 2 represented the technical competence period (cases 35 to 54), and phase 3 was the challenging period (cases 55 to 131). CONCLUSIONS: The Hanoi ASD procedure is safe and feasible for repairing ASD in patients weighing ≥20 kg. According to the learning curve analysis, 34 cases were required to achieve technical efficiency, and 54 cases were required to address highly challenging cases.


Asunto(s)
Defectos del Tabique Interatrial , Cirujanos , Humanos , Curva de Aprendizaje , Estudios Retrospectivos , Resultado del Tratamiento , Defectos del Tabique Interatrial/cirugía
11.
Rep Pract Oncol Radiother ; 28(4): 445-453, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37795228

RESUMEN

Background: The study was to evaluate the effectiveness of dose distribution of four-dimensional computed tomography (4DCT) simulation. Materials and methods: The gross tumor volume (GTV) and clinical target volume (CTV) were contoured in all 10 respiratory phases of 4DCT in 30 patients with non-small cell lung cancer (NSCLC). Both 3D and 4D treatment plans were made individually for each patient using the planning volume (PTV). The PTV3D was taken from a single CTV plus the recommended margin, and the PTV4D was taken from the 4D internal target volume, including all 10 CTVs plus the setup margins. Results: The mean PTV was 460 ± 179 (69-820) cm3 for 3DCT and 401 ± 167 (127-854) cm3 for 4DCT (p = 0.0018). The dose distribution (DD) of organs at risk, especially the lungs, was lower for the 4DCT simulation. The V5%, V10%, and V20% of the total lung dose for 4DCT were significantly lower for the 3DCT. However, lung V30% the heart, esophagus, and spinal cord were not significantly different. In addition, the conformity index and the dose heterogeneity index of the PTV were not significantly different. The normal tissue complication probability (NTCP) of the lung and heart was significantly lower for 4DCT than for 3DCT. Conclusions: The 4DCT simulation gives better results on the NTCP. The organs at risk, especially the lungs, receive a significantly lower DD compared with the 3DCT. The conformity index (CI), heterogeneity index (HI) and the DD to the heart, spinal cord, and esophagus were not significantly different between the two techniques.

12.
J Hand Surg Eur Vol ; 48(2_suppl): 11S-17S, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37704022

RESUMEN

Carpal dislocations result from sequential disruption of the complex relationship between the bones and ligaments of the wrist. Injuries to the carpus occur via predictable mechanisms, an understanding of which is critical to identify and treat these frequently missed patterns of injury and to avoid the sequela of chronic instability. Lunate dislocations are by far the most common, but isolated dislocation of other carpal bones can also occur. Open reduction and internal fixation still remains the gold standard for treatment regardless of the debate around the specific approaches. These high-energy injuries are associated with significant long-term morbidity even when identified promptly and appropriately treated. This review will focus on the evaluation and management of common forms of carpal dislocations.


Asunto(s)
Huesos del Carpo , Luxaciones Articulares , Humanos , Luxaciones Articulares/cirugía , Muñeca , Progresión de la Enfermedad , Fijación Interna de Fracturas
13.
J Neurooncol ; 164(3): 525-533, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37707753

RESUMEN

PURPOSE: Primary brain neoplasms are the most common solid tumors in pediatric patients and seizures are a common presenting symptom. Surgical intervention improves oncologic outcomes and seizure burden. A better understanding of factors that influence seizure outcomes in the surgical management of primary brain tumors of childhood can guide treatment approach thereby improving patient quality of life. METHODS: We performed a systematic analysis using articles queried from PubMed, EMBASE, and Cochrane published from January 1990 to August 2022 to determine predictors of seizure outcomes in pediatric patients undergoing resection of primary brain tumors. RESULTS: We identified 24 retrospective cohort studies, one prospective cohort study, and one mixed retrospective and prospective study for the systematic analysis. A total of 831 pediatric patients were available for analysis. 668 (80.4%) patients achieved seizure freedom after surgery. Complete tumor resection increased the likelihood of a seizure-free (Engel I) outcome compared to subtotal resection (OR 7.1, 95% CI 2.3-21.9). Rates of Engel I seizure outcomes did not significantly differ based on factors such as age at seizure onset, duration of epilepsy, gender, tumor laterality, or age at surgery, but trended towards significance for improved outcomes in temporal lobe tumors. CONCLUSION: Primary brain tumors in the pediatric population are commonly associated with seizures. Resection of these lesions reduces seizure burden and is associated with high rates of seizure freedom. Complete resection, compared to subtotal resection, significantly increases the likelihood of seizure-free outcomes.


Asunto(s)
Neoplasias Encefálicas , Neoplasias Supratentoriales , Niño , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Calidad de Vida , Electroencefalografía , Resultado del Tratamiento , Convulsiones/cirugía , Convulsiones/complicaciones , Neoplasias Supratentoriales/complicaciones , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología
14.
Neuroscience ; 529: 183-199, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37598836

RESUMEN

Recent evidence suggests that alcohol use disorder (AUD) may manifest itself differently in women compared to men. Women experience AUDs on an accelerated timeline and may have certain regional vulnerabilities. In male rats, neuronal cell death and astrocyte reactivity are noted following induction of alcohol dependence in an animal model of an AUD. However, the regional and temporal patterns of neurodegeneration and astrocyte reactivity have yet to be fully examined in females using this model. Therefore, adult female rats were exposed to a 4-day binge model of alcohol dependence followed by different periods of abstinence. Histological markers for FluoroJade B, a label of degenerating neurons, and vimentin, a marker for reactive astrocytes, were utilized. The expression of these markers in cortical and limbic regions was quantified immediately after their last dose (e.g., T0), or 2, 7, and 14 days later. Significant neuronal cell death was noted in the entorhinal cortex and the hippocampus, similar to previous reports in males, but also in several cortical regions not previously observed. Vimentin immunoreactivity was noted in the same regions as previously reported, in addition to three novel regions. Vimentin immunoreactivity also occurred at earlier and later time points in some cortical and hippocampal regions. These data suggest that both neuronal cell death and astrocyte reactivity could be more widespread in females compared to males. Therefore, this study provides a framework for specific regions and time points which should be examined in future studies of alcohol-induced damage that include female rats.


Asunto(s)
Alcoholismo , Humanos , Ratas , Masculino , Femenino , Animales , Alcoholismo/patología , Vimentina , Astrocitos/patología , Etanol , Hipocampo/patología
15.
Cancers (Basel) ; 15(15)2023 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-37568715

RESUMEN

Glioblastoma (GBM) is one of the most progressive and prevalent cancers of the central nervous system. Identifying genetic markers is therefore crucial to predict prognosis and enhance treatment effectiveness in GBM. To this end, we obtained gene expression data of GBM from TCGA and GEO datasets and identified differentially expressed genes (DEGs), which were overlapped and used for survival analysis with univariate Cox regression. Next, the genes' biological significance and potential as immunotherapy candidates were examined using functional enrichment and immune infiltration analysis. Eight prognostic-related DEGs in GBM were identified, namely CRNDE, NRXN3, POPDC3, PTPRN, PTPRN2, SLC46A2, TIMP1, and TNFSF9. The derived risk model showed robustness in identifying patient subgroups with significantly poorer overall survival, as well as those with distinct GBM molecular subtypes and MGMT status. Furthermore, several correlations between the expression of the prognostic genes and immune infiltration cells were discovered. Overall, we propose a survival-derived risk score that can provide prognostic significance and guide therapeutic strategies for patients with GBM.

16.
Innovations (Phila) ; 18(3): 247-253, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37222446

RESUMEN

OBJECTIVE: Minimally invasive cardiac surgery has not been widely applied in repairing sinus venosus atrial septal defect (SV-ASD). Most were minithoracotomy using the single-patch technique for patients with anomalous pulmonary veins (APVs) connecting to the superior vena cava-right atrium (SVC-RA) junction. It is unclear whether patients with APVs draining high to the SVC can be repaired safely and effectively through port access. METHODS: From May 2019 to October 2022, 11 consecutive SV-ASD patients with APVs connecting high to the SVC were enrolled in this prospective study. One 12 mm port and 2 trocars (5.5 mm and 10 mm) were established. The pleural and pericardial spaces were filled with CO2. The SVC was snared just below the azygos vein. The RA incision was longitudinally extended along the SVC-RA junction to the SVC. The bovine pericardial patches were used to redirect the APV flow to the left atrium through the ASD and to enlarge the SVC and the SVC-RA junction. RESULTS: There were no early or late deaths and no reoperations. The concomitant procedures included 5 patients (45.5%) with patent foramen ovale closure, 2 with ASD extension, and 3 with tricuspid valve repair. No endoscopic failure was recorded. The average cardiopulmonary bypass and operative times were 96 (23) min and 190 (30) min, respectively. No cases of venous stenosis or sinus node dysfunction were noted during follow-up of 16.4 ± 12.2 months. CONCLUSIONS: SV-ASD with the APVs draining high to the SVC could be repaired safely and effectively through port access with a double-patch technique.


Asunto(s)
Defectos del Tabique Interatrial , Venas Pulmonares , Malformaciones Vasculares , Humanos , Animales , Bovinos , Vena Cava Superior/cirugía , Estudios Prospectivos , Venas Pulmonares/cirugía , Defectos del Tabique Interatrial/cirugía , Defectos del Tabique Interatrial/complicaciones , Malformaciones Vasculares/complicaciones
17.
J Pain Symptom Manage ; 66(2): 146-159, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37088114

RESUMEN

CONTEXT: Palliative care remains largely inaccessible in low- and middle-income countries (LMICs), and efforts to increase access are impeded by lack of training of proven effectiveness for physicians. OBJECTIVES: To measure the effectiveness of palliative care training for Vietnamese physicians. METHODS: The palliative care-related knowledge, attitudes, and self-assessment of Vietnamese physicians were studied prior to a basic course in palliative care (baseline), just after the physicians completed the course (post), and 6-18 months later (follow-up). RESULTS: The self-assessment scores and knowledge scores increased significantly from baseline to post and decreased significantly from post to follow-up, but the follow-up scores remained significantly higher than baseline. There were significant interactions between changes over time of the knowledge scores and baseline age, degree, years of graduation, training, type of work, and whether participants had ever prescribed morphine for pain. Medically appropriate attitudes increased significantly from baseline to post and did not decrease significantly from post to follow-up. CONCLUSION: Our basic palliative care course in Vietnam resulted in significant and enduring improvements among physicians in palliative care-related knowledge, attitudes, and self-assessed competence. To respond to the enormous unmet need for palliative care in LMICs, primary care providers and physician-specialists in many fields, among others, should receive palliative care training of proven effectiveness, receive ongoing mentoring or refresher training, and be given the responsibility and opportunity to practice what they learn.


Asunto(s)
Cuidados Paliativos , Médicos , Humanos , Cuidados Paliativos/métodos , Vietnam , Conocimientos, Actitudes y Práctica en Salud , Dolor , Actitud del Personal de Salud , Encuestas y Cuestionarios
18.
J Pain Symptom Manage ; 66(3): 175-182.e3, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37119878

RESUMEN

CONTEXT: Hospital-based palliative care (PC) linked to palliative home care is rarely accessible in low- and middle-income countries (LMICs). OBJECTIVES: To study people-centered outcomes of a palliative home care team based at a major cancer center in Vietnam. METHODS: The palliative home care team, consisting of at least one physician and one nurse, provided home PC when needed by patients of the cancer center who lived within 10 kilometers. A linguistically validated version of the African Palliative Outcomes Scale was integrated into standard clinical data collection. We retrospectively reviewed data from the 81 consecutive patients on prevalence and severity of pain and other types of physical, psycho-social, and spiritual suffering at the first home visit (baseline) and at the first follow-up visit and measured any differences. RESULTS: There was great demand for palliative home care. From baseline to follow-up, there was significant improvement in pain regardless of the baseline severity of pain (p < 0.003). Among patients with severe pain, breathlessness, nausea/vomiting, diarrhea, depression, or worry about illness at baseline, there was significant improvement (p < 0.001), and caregiver worry about the patient also improved significantly. CONCLUSION: Integration of hospital- and home-based PC for cancer patients is feasible and improves people-centered outcomes at low cost in Vietnam. These data suggest that benefits to patients, their families, and the health care system can accrue from integration of PC at all levels in Vietnam and other LMICs.


Asunto(s)
Neoplasias , Cuidados Paliativos , Humanos , Estudios Retrospectivos , Vietnam , Dolor , Neoplasias/epidemiología , Neoplasias/terapia , Hospitales
19.
Arthroplast Today ; 20: 101107, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37069946

RESUMEN

Background: There is no consensus on whether unicompartmental arthroplasty (UKA) or high tibial osteotomy (HTO) is superior for unicompartmental arthritis. While there are studies comparing revision and complication rates, none matched a large number of patients undergoing HTO and UKA in the United States and compared these outcomes. We investigated TKA conversion rate and the complications following HTO or UKA. Methods: This retrospective study queried the PearlDiver database of all patients undergoing UKA and HTO using CPT codes between January 2011 and January 2020. We compared propensity-matched populations based on age, gender, Charlson comorbidity index, and Elixhauser comorbidity index to compare odds of complications, TKA conversion, and drug use between UKA and HTO groups. Two-independent sample t-test for unequal variances and test of significance were performed. Results: We found 32,583 UKA patients and 816 HTO patients. Each matched group had 535 patients. One-year complication showed higher risk of pneumonia, hematoma, infection, and mechanical complications among HTO patients. UKA patients used narcotics on average of 10.3 days compared to 9.1 days among HTO patients (P < .01). UKA conversion rates were 4.1%, 5.4%, 7.7%, and 9.2% at 1-, 2-, 5-, and 10-year intervals, respectively. HTO conversion rates were less than 2% at 1- and 2-year intervals, 3.4% at 5-year, and 4.5% at 10-year intervals. This difference was statistically significant at 5- and 10-year intervals (P < .01). Conclusions: Using large matched cohorts, HTO may be converted to TKA later than UKA in short- to mid-term follow-up, and HTO patients used opioids for shorter duration.

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