Robotic radical parametrectomy and pelvic lymphadenectomy in patients with invasive cervical cancer

ObjectiveWe describe a series of patients diagnosed with invasive cervical cancer after undergoing simple hysterectomy who subsequently underwent robotic radical parametrectomy and bilateral pelvic lymphadenectomy. The goal of this study is to report on the safety and feasibility of robotic radical parametrectomy.MethodsA retrospective review was performed of all patients who underwent robotic radical parametrectomy and bilateral pelvic lymphadenectomy at our institution during the period December 2006 to February 2008. We analyzed our data to evaluate the safety and feasibility of performing robotic radical parametrectomy.ResultsThis analysis included 5 patients with invasive squamous cell carcinoma of the cervix. The median body mass index was 23.8 kg/m² (range, 17.7 to 26.5). The median operative time was 365 min (range, 331 to 430). The median estimated blood loss was 100 mL (range, 50 to 175). There were no conversions to laparotomy. There was 1 intraoperative complication—cystotomy. No patient required blood transfusion. The median length of hospital stay was 1 day (range, 1 to 2). One patient experienced two postoperative complications, a vesicovaginal fistula and a lymphocyst. No patient had residual tumor in the parametrectomy specimen, and no patient underwent adjuvant therapy. The median number of pelvic lymph nodes removed was 14 (range, 6 to 16). The median follow-up for all patients was 7.5 months (range, 1.3 to 13.8). There were no recurrences.ConclusionRobotic radical parametrectomy and bilateral pelvic lymphadenectomy is feasible and safe and can be performed with an acceptable complication rate.     

Supracervical hysterectomy in patients with advanced epithelial ovarian cancer

OBJECTIVE: To assess whether supracervical hysterectomy (SCH) is a reasonable alternative to total abdominal hysterectomy in patients with advanced ovarian cancer. METHODS: We reviewed the records of patients with advanced ovarian cancer who underwent a SCH at one institution between 1993 and 2004 and a similar cohort who underwent total abdominal hysterectomy (TAH) at the same institution during the same period. Patients without complete surgical staging done at the institution were excluded. Independent-sample t tests, Fisher exact test, and log rank tests were used for statistical analysis. RESULTS: The study included 47 patients who underwent SCH (mean age, 59.6 years) and 190 who underwent TAH. There were no significant differences between the two groups in age (P=.51), preoperative CA 125 level (P=.55), or receipt of taxane-based and platinum-based chemotherapy (P=.84). Although limited by sample size, there were no significant differences between the two groups in rates of intraoperative complications (4 of 47 in the SCH group, or 8.5%, compared with 7 of 190 in the TAH group, or 3.7%; P=.24), vaginal or cervical recurrence (5 of 47 in the SCH group, or 10.6%, compared with 22 of 190 in the TAH group, or 11.6%; P=1.00), or in progression-free survival (SCH of 1.01 years compared with TAH of 1.19 years; P=.64) or overall survival (SCH of 3.28 years compared with TAH of 3.36 years; P=.12). CONCLUSION: Supracervical hysterectomy may be a reasonable alternative to TAH in patients with advanced ovarian cancer. LEVEL OF EVIDENCE: II.     

Synchrony levels during evoked seizure-like bursts in mouse neocortical slices

Slices (n = 45) from the somatosensory cortex of mouse (P8-13) generated spontaneous bursts of activity (0.10 +/- 0.05 Hz) that were recorded extracellularly. Multiunit action potential (AP) activity was integrated and used as an index of population activity. In this experimental model, seizure-like activity (SLA) was evoked with bicuculline (5-10 microM) or N-methyl-d-aspartate (NMDA, 5 microM). SLA was an episode with repetitive bursting at a frequency of 0.50 +/- 0.06 Hz. To evaluate whether SLA was associated with a change in synchrony, we obtained simultaneous intracellular and extracellular recordings (n = 40) and quantified the relationship between individual cells and the surrounding population of neurons. During the SLA there was an increase in population activity and bursting activity was observed in neurons and areas that were previously silent. We defined synchrony as cellular activity that is consistently locked with the population bursts. Signal-averaging techniques were used to determine this component. To quantitatively assess change in synchronous activity at SLA onset, we estimated the entropy of the single cell's spike trains and subdivided this measure into network burst-related information and noise-related entropy. The burst-related information was not significantly altered at the onset of NMDA-evoked SLA and slightly increased when evoked with bicuculline. The signal-to-noise ratio determined from the entropy estimates showed a significant decrease (instead of an expected increase) during SLA. We conclude that the increased population activity during the SLA is attributed to recruitment of neurons rather than to increased synchrony of each of the individual elements.     

SARS-CoV-2 Spike Protein Disrupts Blood–Brain Barrier Integrity via RhoA Activation

The SARS-CoV-2 spike protein has been shown to disrupt blood–brain barrier (BBB) function, but its pathogenic mechanism of action is unknown. Whether angiotensin converting enzyme 2 (ACE2), the viral binding site for SARS-CoV-2, contributes to the spike protein-induced barrier disruption also remains unclear. Here, a 3D-BBB microfluidic model was used to interrogate mechanisms by which the spike protein may facilitate barrier dysfunction. The spike protein upregulated the expression of ACE2 in response to laminar shear stress. Moreover, interrogating the role of ACE2 showed that knock-down affected endothelial barrier properties. These results identify a possible role of ACE2 in barrier homeostasis. Analysis of RhoA, a key molecule in regulating endothelial cytoskeleton and tight junction complex dynamics, reveals that the spike protein triggers RhoA activation. Inhibition of RhoA with C3 transferase rescues its effect on tight junction disassembly. Overall, these results indicate a possible means by which the engagement of SARS-CoV-2 with ACE2 facilitates disruption of the BBB via RhoA activation. Understanding how SARS-CoV-2 dysregulates the BBB may lead to strategies to prevent the neurological deficits seen in COVID-19 patients.

Graphic Abstract

     

Treatment of hypertension in the elderly: II. Cognitive and behavioral function. Results of a Department of Veterans Affairs Cooperative Study

This study was designed to determine whether blood pressure reduction, per se, causes adverse effects on cognitive and behavioral function in elderly hypertensive patients. Men with mild-to-moderate diastolic hypertension who had passed their 60th birthday were entered into the trial. After a placebo washout period, they were assigned in a randomized, double-blind manner to one of two groups receiving hydrochlorothiazide (either 25 mg once or twice daily or 50 mg once or twice daily). Responders entered a 1-year maintenance period. Nonresponders were randomly assigned to double-blind treatment with hydralazine, methyldopa, metoprolol, or reserpine added to the diuretic therapy. During the placebo and treatment periods, patients underwent a battery of psychometric tests designed to assess cognitive function, motor skills, memory, and affect. A separate questionnaire assessed the patient's ability to perform activities of daily living. A subset of patients blindly being treated with placebo received the same battery of tests as a control for practice effect. The results showed that there was similar improvement on the psychometric tests between those patients whose blood pressure was successfully reduced and the placebo-treated control group. Therefore, the practice effect did not obscure a true deterioration in function. There were no substantive differences between the lower and higher doses of diuretic or among the four drugs added to the diuretic, although there were qualitative differences in side effects. We conclude that blood pressure reduction, per se, does not adversely affect cognitive and behavioral function in elderly hypertensive patients and that antihypertensive treatment is safe and effective in these patients.     

Identifying predictors of treatment outcome in a drug court program

Drug courts are popular for dealing with drug-abusing offenders. However, relatively little is known about participant characteristics that reliably predict either success or failure in these treatment settings. In this article, we report on 99 individuals who were enrolled in a drug court program (approximately one-half of whom successfully completed the program). Using, logistic regression techniques we identified 2 significant predictors of outcome. First, individuals who were employed at the time of their enrollment into the drug court program were more likely to successfully complete the treatment program. Second, individuals with a history of illicit intravenous drug use were less likely to complete the program.     

Nivolumab as adjuvant treatment for a spinal melanocytoma: A case report

Rationale:Meningeal melanocytoma is a rare benign melanocytic tumor of the central nervous system. We report for the first time a case of meningeal melanocytoma treated with immunotherapy.Patient concerns:A 70-year-old man with no medical history was admitted to the Emergency Room. He suffered from a motor and sensory deficit in his left lower limb and a bilateral upper arm neuralgia.Diagnoses:A contrast-enhanced magnetic resonance imaging (MRI) was performed. It showed a C7-T1 bleeding intramedullary tumor. Laminectomy was decided and performed. The results of the pathologic examination showed a melanocytic tumor harboring GNAQ mutation. Meningeal melanocytoma was the final diagnosis.Interventions:The patient was treated with 10 radiotherapy sessions and 6 cycles of nivolumab. A year later, the patient experienced neuralgia again with severe pain and an increasing sensory motor deficit. He underwent a second surgery that was incomplete. As the tumor kept growing, he received temozolomide. But the 6th cycle had to be interrupted due to bedsore infection in the hip area.Outcomes:Disease progression finally led to the patient''s death 3 years after diagnosis.Lessons:This case report is the first about a patient with meningeal melanocytoma treated with immunotherapy. Treatment based on biomolecular mutations will probably change spinal melanocytoma therapeutic approach in the next few years.