Frequency of an intrathecal IgM synthesis and MRZ reaction in children with MS.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. An intrathecal IgM synthesis is associated with a more rapid progression of MS and the intrathecal immune response to measles -, rubella -and varicella zoster virus (MRZR) which, if present, increases the likelihood of a diagnosis of MS in adults. OBJECTIVE: To evaluate the frequency of an intrathecal IgM synthesis and MRZR in children with MS. MethodsChildren with MS and a data set including clinical and treatment history, MRI at onset, in addition to a CSF analysis, and determination of antibody index (AI) of measles, rubella, and zoster antibodies, were eligible. The presence of an intrathecal IgM synthesis and/or a positive MRZ reaction were compared to biomarkers of a more progressive disease course. RESULTS: In 75 children with MS, OCBs were present in 93.3 %). 49,2 % experienced their first relapse within 6 months. 50.7 % had a total lesion load of more than 10 lesions in the first brain MRI. Spinal lesions were identified in 64 %. 23.5 % had a positive MRZR and 40.3 % an intrathecal IgM synthesis. No significant associations were detected between the presence of an intrathecal IgM synthesis and MRZR and parameters including the relapse rate in the first two years. CONCLUSION: An intrathecal IgM synthesis and a positive MRZR are found in a subset of MS children but are not associated with markers associated with a poor prognosis.

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, −0.89 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.

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.

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.

Should Prediabetes be Treated Pharmacologically?

OBJECTIVE: In this commentary I will evaluate whether prediabetes should be treated pharmacologically. To consider this question, certain information concerning prediabetes is relevant. BACKGROUND INFORMATION: (1) Prediabetes is not independently associated with cardiovascular disease; the other factors in the metabolic syndrome increase that risk; (2) various tests and criteria for diagnosing prediabetes are recommended, yielding prevalences varying from 6% to 38% depending on which are used; (3) one-third of patients with prediabetes revert to normal over time; (4) up to two-thirds of patients with prediabetes do not develop diabetes; (5) people with prediabetes have insulin resistance and impaired insulin secretion; (6) although pharmacological treatment of the dysglycemia temporarily lowers it, when the drugs are discontinued, incident diabetes develops similarly as that in those who received placebos; (7) when the drugs are discontinued, there are no changes in insulin resistance or impaired insulin secretion; (8) incident diabetes was similar at 10 years in people remaining on metformin in the Diabetes Prevention Program Outcome Study compared with those who did not receive the drug; (9) no current drugs will directly increase insulin secretion (except sulfonylureas and glinides which have not been used to treat prediabetes because of hypoglycemia concerns); (10) sufficient weight loss to lower insulin resistance by nutritional means is challenging and especially difficult to maintain. CONCLUSIONS: Pharmacological treatment of the dysglycemia of prediabetes is not warranted. On the other hand, the ability of high doses of glucagon-like peptide (GLP)-1 receptor agonists and the combination of a GLP-1 receptor agonist and the glucose-dependent insulinotropic polypeptide (GIP) to lower weight by 15% and 20%, respectively, deserves consideration for the treatment of prediabetes. This amount of weight loss should decrease insulin resistance, allowing endogenous insulin secretion to be more effective and lower the risk for developing diabetes.

The Role of Prediabetes in the Metabolic Syndrome: Guilt by Association.

The metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease (CVD). Prediabetes is defined by either impaired glucose tolerance or by one of the more sensitive or more stringent criterion for impaired fasting glucose (IFG) or HbA1c levels that have been promulgated over the years. IFG is one of the risk factors for CVD included in the definition of the MetS. However, there is very little evidence that IFG is independently associated with CVD regardless of which criterion is used for its diagnosis. The CVD risk of the MetS is related to the other risk factors of central obesity, hypertension, elevated triglyceride, and low high-density lipoprotein cholesterol levels. If the components of the MetS are supposed to be risk factors for CVD, the dysglycemia of prediabetes should not be included in its definition.

Hemolytic anemia following intravenous immunoglobulins in children with PIMS-TS: Two case reports.

This is the first case report on two children presenting with immediate and severe hemolytic anemia following the administration of high-dose intravenous immunoglobulins (IVIGs) in the context of pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). Hemolytic anemia was described as a significant decrease in hemoglobin and an increase in lactate dehydrogenase after the second administration of high-dose IVIGs was performed. Both patients were found to have AB blood group. One of our patients showed massive pallor, weakness, and inability to walk in association with hemolysis. However, in both cases, the anemia was self-limiting and transfusion of red blood cells was not required: both patients recovered without persistent impact. Nonetheless, we aim to draw attention to this widely unknown adverse effect of IVIG, especially in the context of PIMS-TS. We suggest determining the patient's blood group prior to high-dose IVIG infusion and replacing the second IVIG through high-dose steroids or anticytokine therapy. Using IVIGs containing lower titers of specifically anti-A or anti-B antibodies to avoid isoagglutinin-caused hemolytic anemia is desirable; however, the information is not routinely available.

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.

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.

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.

[Potential effect of the stimulus threshold level of the nociceptive flexion reflex (NFRT) on mortality and delirium incidence in the critically ill patient: a retrospective cohort analysis]. / Potenzieller Einfluss der Reizschwellenhöhe des nozizeptiven Flexorenreflex (NFRT) auf die Mortalitäts- und Delirinzidenz beim kritisch kranken Patienten: eine retrospektive Kohortenanalyse.

BACKGROUND: Mortality and delirium in critically ill patients are affected by the provided analgesics and sedatives. The deeper the sedation and the higher the dose of analgesics applied, the more difficult it is to assess pain and the depth of sedation. Therefore, instrumental measurement methods, such as the measurement of the stimulus threshold of the nociceptive flexion reflex (NFRT), are becoming increasingly more important. OBJECTIVE: The aim of the present study is to investigate a potential association between the level of the nociceptive flexion reflex, mortality, and the occurrence of delirium. MATERIAL AND METHODS: By retrospectively analyzing a pilot data set of 57 ICU patients from the interdisciplinary surgical ICU of Ulm University Hospital surveyed between 11/2018 and 03/2020, a possible association between the NFRT, mortality, and the occurrence of delirium was calculated in an adjusted logistic regression model. Depending on the cut-off value, the stimulus threshold corridors result in the following comparison pairs: < 20 mA vs. 20-40 mA/20-50 mA/20-60 mA, > 40 mA vs. 20-40 mA, > 50 mA vs. 20-50 mA and > 60 mA vs. 20-60 mA. Results are presented as odds ratios (OR) adjusted for age, sex, height, TISS-28, SAPS II, RASS, BPS, and applied analgesics. Pain assessment was performed, in addition to the Behavioral Pain scale, ≥ 3 times daily by measuring NFRT. RESULTS: A statistically nonsignificant tendency for an increase in mortality incidence occurred with an NFRT > 50 mA, versus a stimulus threshold corridor of 20-50 mA (OR 3.3, CI: 0.89-12.43, p = 0.07). A trend toward a reduction in delirium incidence occurred at an NFRT < 20 mA, versus a stimulus threshold corridor of 20-40 mA (OR 0.40, CI: 0.18-0.92, p = 0.03). CONCLUSION: Based on the level of the NFRT, no recommendation can be made at this point to adjust the analgesic regimen of critically ill patients, who are unable to communicate. The observation of a tendency towards an increase in mortality at high stimulus thresholds or a reduction in the occurrence of delirium at low stimulus thresholds of the NFRT must be verified in standardized studies.

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.

The impact of endoscopic activity on musculoskeletal disorders of high-volume endoscopists in Germany.

Physical stress is common in GI endoscopists, leading to musculoskeletal disorders. Considering the increasing complexity of interventional GI endoscopy with prolonged examination time, work-related musculoskeletal disorders have come into focus. However, data on work-related health stress in German endoscopists are elusive. The aim of this study was therefore to investigate the prevalence and consequences of work-related musculoskeletal disorders in German endoscopists. A 24-item questionnaire on endoscopy-associated musculoskeletal disorders and standardized pain assessment was developed by an interdisciplinary team of endoscopists and sports medics. The survey was distributed online by the leading German societies for gastroenterology and endoscopy. Overall, 151 German practicing endoscopists took part in the study. Regarding the average number of endoscopic procedures per week, the study collective consisted mainly of high-volume endoscopists. The survey showed that most participants suffered from general musculoskeletal disorders (82.8%) and from work-related musculoskeletal disorders (76.8%). The most affected body parts were the neck, low back, thumb, and shoulder. Temporary absence from work due to symptoms was reported by 9.9% of the respondents. Over 30% of participating endoscopists stated the need for analgesics or physiotherapy due to musculoskeletal disorders. Age, professional experience and work time were identified as relevant risk factors for musculoskeletal health issues. A high number of German endoscopists are affected by musculoskeletal disorders due to specific working postures and repetitive movements with a large impact on personal health. Further interventional studies are mandatory to improve the risk prevention of endoscopic activity.