Surgical management of uterine fibroids.

PURPOSE OF REVIEW: Fibroids are benign pelvic masses and constitute the most common gynaecological condition. They create a significant health and social burden to many women because of heavy menstrual bleeding and fibroid pressure symptoms. Many women will be faced with the dilemma of surgical management to improve their symptoms at some point of their reproductive age. The aim of this article is to identify current surgical management of fibroids describing the technical steps, advantages, disadvantages and risks of each method. RECENT FINDINGS: The surgical management of fibroids remains challenging, as the overall prevalence, the clinical experience and the patient awareness is increasing because of an upgrade in our sonographic and magnetic resonance diagnostic tools. Unfortunately not every patient is able to benefit from tailor-made surgery that holistically evaluates individual needs including fertility aspirations. SUMMARY: This article provides the most current synopsis of every available surgical modality for fibroid management. Large prospective multicentre cohort studies are needed to definitely determine the most suitable operation for any individual suffering with fibroids; and perhaps artificial intelligence may offer a valuable tool in the future data analysis.

Focal Cortex Stimulation With a Novel Implantable Device and Antiseizure Outcomes in 2 Prospective Multicenter Single-Arm Trials.

Importance: For the large population of people with drug-refractory epilepsy, alternative treatment approaches are needed. Clinical trial outcomes of a novel stimulation device, which is newly available in Europe for the treatment of patients with a predominant seizure focus, are reported for the first time. Objective: To perform a pooled analysis of the results of 2 prospective, multicenter, single-arm trials, A Pilot Study to Assess the Feasibility of Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (EASEE II) and A Pilot Study to Assess the Feasibility of Patient-Controlled Neurostimulation With the EASEE System to Treat Medically Refractory Focal Epilepsy (PIMIDES I), assessing the safety and efficacy of epicranial focal cortex stimulation (FCS) with a novel implantable device (EASEE [Precisis]) as adjunctive treatment for adult patients with drug-refractory focal epilepsy. Design, Setting, and Participants: This study was a pooled analysis of 2 nonrandomized uncontrolled trials, EASEE II and PIMIDES I, which began on January 15, 2019, and January 14, 2020, respectively, and ended on July 28, 2021. EASEE II and PIMIDES I were the first in-human, prospective, single-arm trials with an 8-month evaluation period. Patients were recruited at 7 European epilepsy centers. Consecutive participants with drug-refractory focal epilepsy were enrolled. Study data were analyzed from September 29, 2021, to February 2, 2022. Interventions: After a 1-month prospective baseline period, patients were implanted with the neurostimulation device. After a 1-month postimplantation recovery period, unblinded FCS was activated using both high-frequency and direct current (DC)-like components performed via electrode arrays placed epicranially above the individual epileptic focus region. Main Outcomes and Measures: Efficacy was prospectively assessed by the responder rate in the sixth month of stimulation compared with baseline; safety and additional end points were assessed after device implantation and during the stimulation period. Results: Of the 34 adult patients enrolled at 6 German and 1 Belgian investigational site, 33 (mean [SD] age, 34.6 [13.5] years; 18 male patients [54.5%]) received the neurostimulation device implant. A total of 32 patients underwent combined high-frequency direct current-like stimulation at least until the 8-month postimplant follow-up visit. After 6 months of stimulation, 17 of 32 patients (53.1%) were responders to treatment with at least a 50% reduction in seizure frequency compared with baseline, corresponding to a significant median seizure reduction by 52% (95% CI, 0.37%-0.76%; P < .001). No device- or procedure-related serious adverse events were reported (0; 95% CI, 0%-10.58%). There were no significant alterations in cognition, mood, or overall quality of life. Conclusions and Relevance: Results of this pooled analysis of 2 nonrandomized uncontrolled trials suggest that FCS with a novel neurostimulation device was associated with an effective reduction in seizure frequency in patients with drug-refractory focal epilepsy and may offer a promising treatment option for patients with a predominant epileptic focus. Trial Registration: German Clinical Trials Register: DRKS00015918 and DRKS00017833, respectively, and jointly under PROSPERO: CRD42021266440.

Effect of Local Anesthetics on Postoperative Pain in Patients Undergoing Gynecologic Laparoscopy: A Systematic Review and Meta-analysis of Randomized Trials.

OBJECTIVE: Pain remains a common complication after gynecologic laparoscopy. Use of local anesthesia may be beneficial in reducing postoperative pain. We performed a systematic review and meta-analysis to assess whether local anesthetic decreases postoperative pain after laparoscopic gynecologic procedures. DATA SOURCES: We searched Cumulative Index to Nursing and Allied Health Literature, Embase, and Medline from inception to November 2020 using Medical Subject Headings and free text combinations. METHODS OF TRIAL SELECTION: We included randomized controlled trials of patients undergoing gynecologic laparoscopy receiving port site subcutaneous, subfascial, or intraperitoneal local anesthetic compared with placebo or no intervention. We included 20 trials (1861 participants) with size varying between 28 and 164 participants. TABULATIONS, INTEGRATION, AND RESULTS: Meta-analysis was performed with RevMan 5.3 (Cochrane Collaboration, London, United Kingdom), with standard mean differences (SMDs) and random-effects model. Port site infiltration reduces postoperative pain at 4 hours (SMD -0.25; 95% confidence interval [CI], -0.44 to -0.06; 4 trials; 545 participants) and 6 hours (SMD -0.44; 95% CI, -0.82 to -0.06; 4 trials; 455 participants) after surgery. The administration of intraperitoneal local anesthetics reduces pain at 6 hours (-1.42; 95% CI, -3.22 to -0.30; 4 trials; 277 participants) after surgery. CONCLUSIONS: The use of port site and intraperitoneal local anesthetic decreases immediate postoperative pain in patients undergoing gynecologic laparoscopy, although its impact on analgesia requirements is unclear. Routine usage of local anesthetics should be considered for people undergoing gynecologic laparoscopy.

No Clinically Relevant Interactions of St. John's Wort Extract Ze 117 Low in Hyperforin With Cytochrome P450 Enzymes and P-glycoprotein.

Hypericum perforatum L. (St. John's wort) is used to treat mild-to-moderate depression. Its potential safety risks are pharmacokinetic drug interactions via cytochrome P450 (CYP) enzymes and P-glycoprotein, presumably caused by hyperforin. In a phase I, open-label, nonrandomized, single-sequence study, the low-hyperforin Hypericum extract Ze 117 was investigated using a drug cocktail in 20 healthy volunteers. No pharmacokinetic interactions of Ze 117 were observed for CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, and P-glycoprotein. Area under the curve (AUC) and peak plasma concentration (Cmax ) of the used probe drugs showed 90% confidence intervals (CIs) of the geometric mean ratios of the drugs taken together with Ze 117 vs. probe drug alone, well within the predefined bioequivalence range of 80-125%. Though Ze 117 did not induce dextromethorphan metabolism by CYP2D6, it weakly increased dextromethorphan AUC ratio (mean 147.99, 95% CI 126.32-173.39) but not the corresponding metabolic ratio. Ze 117 does not show clinically relevant pharmacokinetic interactions with important CYPs and P-glycoprotein.

Music as an aid for postoperative recovery in adults: a systematic review and meta-analysis.

BACKGROUND: Music is a non-invasive, safe, and inexpensive intervention that can be delivered easily and successfully. We did a systematic review and meta-analysis to assess whether music improves recovery after surgical procedures. METHODS: We included randomised controlled trials (RCTs) of adult patients undergoing surgical procedures, excluding those involving the central nervous system or head and neck, published in any language. We included RCTs in which any form of music initiated before, during, or after surgery was compared with standard care or other non-drug interventions. We searched MEDLINE, Embase, CINAHL, and Cochrane Central. We did meta-analysis with RevMan (version 5.2), with standardised mean differences (SMD) and random-effects models, and used Stata (version 12) for meta-regression. This study is registered with PROSPERO, number CRD42013005220. FINDINGS: We identified 4261 titles and abstracts, and included 73 RCTs in the systematic review, with size varying between 20 and 458 participants. Choice of music, timing, and duration varied. Comparators included routine care, headphones with no music, white noise, and undisturbed bed rest. Music reduced postoperative pain (SMD -0·77 [95% CI -0·99 to -0·56]), anxiety (-0·68 [-0·95 to -0·41]), and analgesia use (-0·37 [-0·54 to -0·20]), and increased patient satisfaction (1·09 [0·51 to 1·68]), but length of stay did not differ (SMD -0·11 [-0·35 to 0·12]). Subgroup analyses showed that choice of music and timing of delivery made little difference to outcomes. Meta-regression identified no causes of heterogeneity in eight variables assessed. Music was effective even when patients were under general anaesthetic. INTERPRETATION: Music could be offered as a way to help patients reduce pain and anxiety during the postoperative period. Timing and delivery can be adapted to individual clinical settings and medical teams. FUNDING: None.

Noise-induced precursors of tonic-to-bursting transitions in hypothalamic neurons and in a conductance-based model.

The dynamics of neurons is characterized by a variety of different spiking patterns in response to external stimuli. One of the most important transitions in neuronal response patterns is the transition from tonic firing to burst discharges, i.e., when the neuronal activity changes from single spikes to the grouping of spikes. An increased number of interspike-interval sequences of specific temporal correlations was detected in anticipation of temperature induced tonic-to-bursting transitions in both, experimental impulse recordings from hypothalamic brain slices and numerical simulations of a stochastic model. Analysis of the modelling data elucidates that the appearance of such patterns can be related to particular system dynamics in the vicinity of the period-doubling bifurcation. It leads to a nonlinear response on de- and hyperpolarizing perturbations introduced by noise. This explains why such particular patterns can be found as reliable precursors of the neurons' transition to burst discharges.

A phase II, double-masked, randomized, placebo-controlled evaluation of a human monoclonal anti-Cytomegalovirus antibody (MSL-109) in combination with standard therapy versus standard therapy alone in the treatment of AIDS patients with Cytomegalovirus retinitis.

ACTG 266 was designed as a randomized study to evaluate two doses of the human monoclonal antibody directed against CMV gH (MSL-109) versus placebo, each in combination with standard antiviral therapy for the treatment of newly diagnosed Cytomegalovirus (CMV) retinitis in AIDS patients. A total of 82 subjects were enrolled and received either placebo (n = 28), or MSL-109 at 15 mg (n = 26) or 60 mg (n = 28) every 2 weeks until disease progression was diagnosed. The primary endpoint, disease progression, was determined by masked reading of retinal photographs taken every 4 weeks read by a single investigator. The median time to progression was 8.0, 8.3, and 12.1 weeks in the placebo, MSL-109 15mg and MSL-109 60 mg cohorts, respectively (P = 0.087, placebo versus 60 mg cohort). There were 22 deaths during the study period (9, 9, and 4 in the placebo, MSL-109 15 mg and MSL-109 60 mg cohorts, respectively (P = 0.0058, placebo versus 60 mg cohort)). MSL-109 was well tolerated with no significant adverse events attributable to study medication. The unexplained survival advantage in the higher dose cohort was discordant with the findings of the parallel Studies of Ocular Complications of AIDS Research Group (SOCA)-Monoclonal Anti-CMV Retinitis Trial (MACRT), which was prematurely halted because of increased mortality in subjects treated with high-dose MSL-109, recognizing that A266 enrolled subjects with newly diagnosed, whereas the MACRT enrolled subjects with relapsed, CMV retinitis.

Questions to and answers from the International AIDS Society-USA Resistance Testing Guidelines Panel.

In 1996 the International AIDS Society-USA convened an international panel of experts in HIV drug resistance and clinical management to develop guidelines for the clinical use and limitations of resistance testing. Since then the International AIDS Society-USA Resistance Testing Guidelines Panel has developed and regularly published its recommendations. The latest panel recommendations appear in the July 1 issue of Clinical Infectious Diseases. We periodically pose questions to the panel relating to clinical elements of resistance testing that have been collected from HIV practitioners across the nation. We are happy to feature the latest edition in this issue of Topics in HIV Medicine. It is our hope that addressing these issues will help guide your treatment strategy decisions regarding resistance testing.