Exploring complications following cranioplasty after decompressive hemicraniectomy: A retrospective bicenter assessment of autologous, PMMA and CAD implants.

Cranioplasty (CP) after decompressive hemicraniectomy (DHC) is a common neurosurgical procedure with a high complication rate. The best material for the repair of large cranial defects is unclear. The aim of this study was to evaluate different implant materials regarding surgery related complications after CP. Type of materials include the autologous bone flap (ABF), polymethylmethacrylate (PMMA), calcium phosphate reinforced with titanium mesh (CaP-Ti), polyetheretherketone (PEEK) and hydroxyapatite (HA). A retrospective, descriptive, observational bicenter study was performed, medical data of all patients who underwent CP after DHC between January 1st, 2016 and December 31st, 2022 were analyzed. Follow-up was until December 31st, 2023. 139 consecutive patients with a median age of 54 years who received either PMMA (56/139; 40.3%), PEEK (35/139; 25.2%), CaP-Ti (21/139; 15.1%), ABF (25/139; 18.0%) or HA (2/139; 1.4%) cranial implant after DHC were included in the study. Median time from DHC to CP was 117 days and median follow-up period was 43 months. Surgical site infection was the most frequent surgery-related complication (13.7%; 19/139). PEEK implants were mostly affected (28.6%; 10/35), followed by ABF (20%; 5/25), CaP-Ti implants (9.5%; 2/21) and PMMA implants (1.7%, 1/56). Explantation was necessary for 9 PEEK implants (25.7%; 9/35), 6 ABFs (24.0%; 6/25), 3 CaP-Ti implants (14.3%; 3/21) and 4 PMMA implants (7.1%; 4/56). Besides infection, a postoperative hematoma was the most common cause. Median surgical time was 106 min, neither longer surgical time nor use of anticoagulation were significantly related to higher infection rates (p = 0.547; p = 0.152 respectively). Ventriculoperitoneal shunt implantation prior to CP was noted in 33.8% (47/139) and not significantly associated with surgical related complications. Perioperative lumbar drainage, due to bulging brain, inserted in 38 patients (27.3%; 38/139) before surgery was protective when it comes to explantation of the implant (p = 0.035). Based on our results, CP is still related to a relatively high number of infections and further complications. Implant material seems to have a high effect on postoperative infections, since surgical time, anticoagulation therapy and hydrocephalus did not show a statistically significant effect on postoperative complications in this study. PEEK implants and ABFs seem to possess higher risk of postoperative infection. More biocompatible implants such as CaP-Ti might be beneficial. Further, prospective studies are necessary to answer this question.

In adults with BMI ≥27 kg/m2 and type 2 diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk.

SOURCE CITATION: Garvey WT, Frias JP, Jastreboff AM, et al; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402:613-626. 37385275.

Beneficial Effect of Remote Glucose Monitoring and Computerized Insulin Dose Adjustment Algorithms Independent of Insulin Dose Increases in Sizeable Minorities of Patients.

This article describes a program through which interactions every 2-3 weeks between patients and primary care clinicians (PCCs), with recommendations based on analysis of remote glucose monitoring by computerized insulin dose adjustment algorithms, significantly improved diabetes control. Insulin doses increased by 30% in the majority of patients. A sizeable minority (36%) had a decrease or no increase in insulin doses, but still showed an improvement in diabetes control. Frequent interactions allowed PCCs the opportunity to recognize and address medication nonadherence.

Mepolizumab improves sense of smell in severe chronic rhinosinusitis with nasal polyps: SYNAPSE.

BACKGROUND: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. RESULTS: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: -0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,-1.29 vs -0.23 vs -0.07; =3 years since last surgery, -.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. CONCLUSIONS: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

[Chronic rhinosinusitis with nasal polyposis : A retrospective analysis of therapeutic approaches in 463 patients]. / Chronische Rhinosinusitis mit Polyposis nasi : Retrospektive Analyse des therapeutischen Vorgehens bei 463 Patienten.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease, the treatment of which has undergone significant changes in recent years. In addition to surgical approaches, topical and systemic steroids, and adaptive acetylsalicylic acid (ASA) desensitization, three specific antibodies have complemented the therapeutic portfolio since 2019. METHODS: A retrospective evaluation of all patients who presented as outpatients for the first time due to CRSwNP in 2007 and 2008 (collective A) and 2017 and 2018 (collective B) was performed, up to and including June 2023. RESULTS: The clinical courses of 463 patients (mean age 49.1 years, range 5-82 years; 65.9% male) were included in the analysis. Conservative treatment with nasal corticosteroids started before initial presentation was more frequent in collective B (collective A 43.9% vs. collective B 72.2%). In 278 of the 463 patients (60%; A: 62%, B: 58%), at least one operation on the nasal sinuses had been performed after initial presentation; in 101 of these patients (36.3%) recurrent polyposis (within mean follow-up of 2.4 years) required further treatment. The indication for ASA provocation/desensitization was applied less frequently in collective B, also due to a high discontinuation rate (at least 38%) of the maintenance therapy. Of the total cohort, 16 patients (3.5%; A: n = 8, B: n = 8) were meanwhile switched to antibody therapy at recurrence. CONCLUSION: A step-by-step guideline-orientated approach is recommended in the treatment of CRSwNP. Systemic antibodies as an add-on to nasal corticosteroids are a relatively new therapeutic option for treatment-refractory CRSwNP, which reduces the indication for ASA desensitization, which is associated with a relatively high incidence of side effects and poor compliance.

In adults with obesity without diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk.

SOURCE CITATION: Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-16. 35658024.

Erratum - Tri-Lineage Differentiation of NTERA2 Clone D1 Cells towards Neural, Hepatic and Osteogenic Lineages in Vitro.

The images in Fig. 4 were not presented correctly. The correct version of Fig. 4: see the last page of pdf. The original article was published in Folia Biologica (Praha) Volume 67, No. 5-6 (2021), 174-182. https://doi.org/10.14712/fb2021067050174.

Trauma treatment using Narrative Exposure Therapy adapted to persons with intellectual disabilities or severe chronic mental disorders - a randomised controlled pilot study with an embedded observational study.

BACKGROUND: Despite an increased likelihood of experiencing traumatic events and increased vulnerability, there are only few publications on trauma therapy for persons with intellectual disabilities (IDs). This pilot study for the first time investigates the feasibility and effectiveness of Narrative Exposure Therapy (NET) within this target group modified by Plain Language. METHODS: A group of n = 10 participants with ID dual diagnoses and another group of n = 5 participants with severe and chronic mental disorders were separately stratified and randomised, then forming together an intervention group (n = 7) and a waiting list control group (n = 8). All participants were treated with NET attuned to their communication abilities by using Plain Language. Primary outcome was the post-traumatic stress measured with the Post-Traumatic Symptom Scale-10 before and after the intervention. In addition, the Adverse Childhood Experience Index was used for diagnostic purposes. Data were analysed using t-test for repeated measures and analysis of covariance. RESULTS: Narrative Exposure Therapy and the randomised controlled trial study proved to be successfully conductible with participants with IDs in a congregated residential service. Although the corresponding effect size was high (partial eta square = 0.188), the between-group difference was not significant (P = 0.12). Analysis of the observational study resulted in a highly significant improvement for participants with IDs (P < 0.001; Hedges' g = 2.36) and in a significant improvement in participants with severe and chronic mental disorders (P < 0.013; Hedges' g = 1.52). Additionally, the participants with IDs show a significantly better reduction of symptom burden (P = 0.03; partial eta square = 0.327). CONCLUSIONS: The results provide a first evidence for a possible and successful implementation of NET modified in Plain Language for persons with IDs and complex mental health support needs. Completeness in responding to the items of Post-Traumatic Symptom Scale-10 and Adverse Childhood Experience Index indicates the suitability of these instruments for both groups of participants. Although the group difference in the randomised controlled trial failed to achieve statistical significance mainly due to the small sample size, the results of the embedded observational study are promising for the conduct of further studies with the modified NET.

Evaluating treatment response to mepolizumab in patients with severe CRSwNP.

BACKGROUND: The SYNAPSE study (NCT03085797) demonstrated that mepolizumab decreased nasal polyp (NP) size and nasal obstruction in patients with chronic rhinosinusitis with NP (CRSwNP). METHODS: SYNAPSE, a randomized, double-blind study, included patients with recurrent, refractory, severe CRSwNP, eligible for repeated surgery despite receiving standard of care (SoC). Patients received 4-weekly mepolizumab 100 mg or placebo subcutaneously plus SoC for 52 weeks. This post hoc analysis further characterized treatment responses and association with patient characteristics. The proportion of patients meeting any and each of five response criteria indicating improvement in disease-specific quality of life, NP size, nasal obstruction, loss of smell, and overall symptoms at Weeks 24 and 52, were assessed in subgroups: 1) no surgery; 2) neither surgery nor systemic corticosteroids (SCS). RESULTS: Of 407 patients in the intention-to-treat population, 381 and 343 patients had no sinus surgery by Weeks 24 and 52, respectively. More mepolizumab- versus placebo-treated patients without surgery by Weeks 24 and 52 met each response criteria. Of the mepolizumab-treated patients without surgery by Week 24, 109 (55%) responded across >=3 criteria, increasing to 126 (67%) by Week 52. Similar response trends were seen for patients with neither surgery nor SCS by Weeks 24 and 52. At either timepoint, there were no major differences in baseline characteristics between mepolizumab-treated full- (5/5 categories) and non-responders (0/5 categories). CONCLUSIONS: Most patients who completed SYNAPSE required neither surgery nor SCS use and in addition achieved a progressive and sustained clinical response to mepolizumab underscoring the therapeutic benefits of mepolizumab in severe CRSwNP.

Morphometric analyses in patients treated with subthreshold laser photocoagulation for central serous chorioretinopathy.

BACKGROUND AND OBJECTIVE: To analyze changes in selected parameters in optical coherence tomography (OCT) after subthreshold laser coagulation (ST-LP) in patients with central serous chorioretinopathy (CSCR). MATERIALS AND METHODS: Fifty-four eyes of 49 patients with CSCR were included in the study. Each patient underwent therapy with ST-LP with a frequency-doubled Neodym-YAG Laser and OCT imaging. In OCT the thickness of the central subfield, cube volume, average cube thickness, volume under the ETDRS grid, and average thickness under the ETDRS grid were collected. RESULTS: Decreases in total OCT volume and central retinal subfield thickness were statistically significant (p < 0.05). Possible correlations were observed between visual acuity at V3 (3 months after ST-LP) and Baseline and between central retinal subfield thickness at V1 (4 weeks after ST-LP) and visual acuity at BL. CONCLUSION: A decrease in retinal thickness and retinal volume could be shown after ST-LP. Central retinal subfield thickness measured by OCT could be a more sensitive measure than mean retinal thickness or macular volume for early detection of disease recurrence occurring in some patients 3 months after ST-LP.

PSA and PSA Kinetics as Predictors for 18F-Fluciclovine PET/CT Positivity in Biochemically Recurrent Prostate Cancer.

INTRODUCTION: 18F-Fluciclovine PET/CT is one of the imaging techniques currently employed to restage prostate cancer (PCa). Due to the conflicting results reported in the literature, it is not yet known at what PSA threshold 18F-fluciclovine PET/CT could reliably demonstrate the presence of recurring disease. We explored the association between 18F-fluciclovine PET/CT positivity and prescan PSA, PSA doubling time, and PSA velocity in patients with biochemical recurrence (BCR) of PCa after curative-intent treatment. METHODS: Data from 59 patients who underwent 18F-fluciclovine PET/CT for BCR after radical prostatectomy or radiotherapy were retrieved from a single institution database. Patients already undergone salvage treatments at the time of PET/CT, with newly diagnosed PCa or with initial diagnosis of metastatic PCa were excluded. A 2-sided independent samples Bayesian t test and Bayesian Mann-Whitney U test were used to assess the association between PET/CT and prescan PSA, PSA doubling time, and PSA velocity. RESULTS: Evidence for no difference between PET/CT-positive and -negative patients for log-transformed PSA was found (BF01 3.61, % error: 0.01). Robustness check and sequential analysis showed stability across a wide range of prior distribution specifications. The hypothesis of no difference in terms of PSA-dt and for PSA-vel between groups was found to be more likely compared to the alternative hypothesis (BF01 of 3.44 and 3.48, respectively). CONCLUSION: PSA and PSA kinetics are unlikely to be associated with 18F-fluciclovine PET/CT positivity in patients with BCR, and none of these serum biomarkers might be used as single predictors of PET/CT detection. Larger studies might be needed to evaluate the role of different predictors.

A Conversation on an Effective, Straightforward, Quantitative Approach to the Outpatient Use of Insulin.

For primary care providers, using insulin can present challenges that can be met by a straightforward approach using the following principles. Depending on when it is injected, each component of the insulin regimen has a maximal effect on a specific period of the 24-hour cycle (e.g., overnight, morning, afternoon, or evening). The glucose pattern in that period determines whether the dose of that component of the insulin regimen requires adjusting. Regarding which insulin types and insulin regimens to use, human insulin (NPH and regular) is as effective as analog insulins, and a two-injection intensified insulin regimen is as effective as a four-injection regimen.

Mepolizumab improves quality of life and reduces activity impairments in patients with CRSwNP.

Mepolizumab improves quality of life and reduces activity impairments in patients with CRSwNP.

Tri-Lineage Differentiation of NTERA2 Clone D1 Cells towards Neural, Hepatic and Osteogenic Lineages in Vitro.

Over the past decades, the in vitro use of pluripotent cell lines gained a crucial role in toxicology, preclinical drug testing and developmental biology. NTERA2 clone D1 cells were identified as pluripotent cells with high potential for neural differentiation. Although they are commonly used cellular sources in neuropharmacology and neurodevelopmental studies, their endodermal and mesodermal differentiation potential awaits further characterization. Here, we devised improved protocols for hepatogenic and osteogenic differentiation of NTERA2 clone D1 cells. Our in vitro differentiation assays showed significant up-regulation of multiple hepatogenic markers. We also observed robust mineralization and osteogenic marker expression of NTERA2 clone D1 cells upon in vitro osteogenic induction. These results suggest that NTERA2 clone D1 cells may be utilized as an in vitro model system to study various aspects of liver biology and osteogenesis. In addition, tri-lineage differentiation of NTERA2 clone D1 cells may serve as a simple experimental control system when validating pluripotency of other cell types.

Effect of Diabetes-Trained Nurse Practitioners on Glycemic Outcomes: Their Suggested Use in Busy Primary Care Practices.

A Federally Qualified Health Center received ongoing external support for half-time salaries for two nurse practitioners to treat people with poorly controlled diabetes (A1C >9.0%) in the clinic's diabetes program using approved detailed treatment protocols. Patients were treated for 1 year and graduated from this program if their A1C fell to <7.5%. Ninety-one percent graduated, and treatment was deemed to have failed in 9% who did not achieve an A1C <7.5% by the end of the year of treatment. The suggestion is made to assign a specially trained diabetes nurse or physician assistant to serve many primary care providers at important clinical junctures to improve diabetes outcomes throughout busy primary care practices.

Ureteral location is associated with survival outcomes in upper tract urothelial carcinoma: A population-based analysis.

OBJECTIVES: To evaluate the prognostic value of tumor location in patients with upper tract urothelial carcinoma. METHODS: Within the Surveillance, Epidemiology and End Results Incidence Database, 6619 upper tract urothelial carcinoma cases were identified, including 3719 confined to the renal pelvis and 2971 to the ureter. Predictors of surgical technique (kidney sparing surgery versus radical nephroureterectomy), as well as 2- and 5-year cancer-specific survival and overall survival were evaluated. RESULTS: Median follow-up time was 29 months (interquartile range 0-126 months) for both groups. Multivariate logistic analysis showed tumor dimension as the only factor associated with radical nephroureterectomy (odds ratio 1.02; P < 0.001). Ureteral 2- and 5-year overall survival were lower (log-rank P = 0.001) compared with renal pelvis. When stratifying tumor location according to dimensions, a ureteral carcinoma >3 cm was associated with the worst 2- and 5-year cancer-specific mortality (Pepe-Mori P < 0.001), and overall survival (log-rank P < 0.001). The 2- and 5-year cancer-specific mortality (Pepe-Mori P < 0.001) and overall survival were the worst for ureteral ≥T3 tumors (log-rank P < 0.001). The 2- and 5-year cancer-specific mortality (Pepe-Mori P < 0.001) and overall survival (log-rank P < 0.001) were the worst for ureteral grade III-IV cancers. Ureteral tumor location (subdistribution hazard ratio 1.18, P < 0.001), tumor dimension ≥3 (subdistribution hazard ratio 1.25, P < 0.001), T staging (T2-4 all P < 0.001), grading (grade III subdistribution hazard ratio 2.20, P = 0.001; grade IV subdistribution hazard ratio 2.39, P < 0.001) were found to be associated with higher cancer mortality. CONCLUSIONS: Ureteral tumor location in upper tract urothelial carcinoma seems to be associated with worse oncological outcomes, especially in the case of advanced disease. Although the type of surgical treatment does not seem to impact survival, surgeons should use caution in adopting a kidney-sparing surgery for patients with ureteral upper tract urothelial carcinoma.

A Critical Review of State-of-the-Art and Emerging Approaches to Identify Fracking-Derived Gases and Associated Contaminants in Aquifers.

High-volume, hydraulic fracturing (HVHF) is widely applied for natural gas and oil production from shales, coals, or tight sandstone formations in the United States, Canada, and Australia, and is being widely considered by other countries with similar unconventional energy resources. Secure retention of fluids (natural gas, saline formation waters, oil, HVHF fluids) during and after well stimulation is important to prevent unintended environmental contamination, and release of greenhouse gases to the atmosphere. Here, we critically review state-of-the-art techniques and promising new approaches for identifying oil and gas production from unconventional reservoirs to resolve whether they are the source of fugitive methane and associated contaminants into shallow aquifers. We highlight future research needs and propose a phased program, from generic baseline to highly specific analyses, to inform HVHF and unconventional oil and gas production and impact assessment studies. These approaches may also be applied to broader subsurface exploration and development issues (e.g., groundwater resources), or new frontiers of low-carbon energy alternatives (e.g., subsurface H2 storage, nuclear waste isolation, geologic CO2 sequestration).

Erratum: Delayed Response to U-500 Regular Insulin. Clinical Diabetes 2018;36: 77-79 (DOI: 10.2337/cd16-0058).

[This corrects the article on p. 77 in vol. 36, PMID: 29382984.].