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Topicality of the fundamental and determining importance of chronic critical ischemia of the extremities and its restorative treatment using crural/pedal bypasses in Germany and in Saxony-Anhalt

Chirurgie (Heidelb). 2023 Aug 23. doi: 10.1007/s00104-023-01933-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Currently, there is an increase in severe stages of peripheral arterial occlusive disease (PAOD) with critical ischemia. This seems to correspond to the general demographic change as well as a consequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic of the last 3 years. The now established and accepted interventional/endovascular approach for severe lower leg PAOD in experienced hands is still considered the first-line treatment but from the authors’ perspective crural/pedal venous bypass is experiencing a renaissance.

MATERIAL AND METHODS: Compact narrative review of the current state of crural/pedal bypass surgery in Germany and Saxony-Anhalt (SA) combined with selective references from the current scientific medical literature and own clinical experiences.

RESULTS: The current statistics of case-related diagnosis-related groups (DRG) data show that, especially with the occurrence of the corona pandemic, a decrease in inpatient case numbers of patients with PAOD stage IIB can be observed nationwide and also in SA. The severe PAOD stages have remained approximately the same in case numbers but increased in SA. The risk stratification based on the wound, ischemia and foot infection (WIFI) classification offers the possibility to be able to make statements about the risk of amputation, benefits and type of revascularization measures. The length of the occlusion, occlusion site of the affected vessels and degree of calcification are taken into account in the global limb anatomic staging system (GLASS) to assess the prognosis. The evaluation of the case-based hospital statistics from 2015 to 2020 showed a constant use of femorocrural/femoropedal bypass surgery in Germany as well as a slight increase in reconstruction using femorocrural bypasses in SA, which seems to correlate with the tendency for an increase in the number of cases of severe PAOD. Parameter-based objectification of the severity of critical limb ischemia should be included in the indications for placement of a crural/pedal bypass. The WIFI classification and GLASS are suitable for this purpose as a relative prognosis of success is also possible. The treatment of critical limb ischemia by crural/pedal bypass surgery continues to find a constant application in Germany and SA.

PMID:37610660 | DOI:10.1007/s00104-023-01933-7

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Five-year change of panoramic radiomorphometric indices and fractal dimension values in type 2 diabetes patients

Oral Radiol. 2023 Aug 23. doi: 10.1007/s11282-023-00707-5. Online ahead of print.

ABSTRACT

OBJECTIVES: Diabetes mellitus is a chronic disease characterized by dysregulation of glucose metabolism, with characteristic long-term complications accompanied by changes in bone quality. The purpose of this study is to compare the results with a control group by performing radiomorphometric analyses on panoramic radiographs obtained 5 years apart to examine changes in the mandibular bone cortex and microstructures of type 2 diabetes mellitus (T2DM) patients.

METHODS: Two panoramic radiographs that were taken 5 years (mean 5.26 ± 0.134) apart from 52 patients with T2DM (n:26) and a control group (n:26) were used. A total of 104 images were evaluated. Analyses were done from the condyle (FD1), angulus (FD2), distal second premolar apex (FD3), and anterior to the mental foramen (FD4) for fractal dimension (FD) in the mandible. Symphysis index (SI), anterior index (AI), molar index (MI), posterior index (PI), and panoramic mandibular index (PMI) measurements were taken for cortical analysis. Three-way ANOVA, three-way robust ANOVA, two-way ANOVA, and two-way robust ANOVA tests were used for statistical analysis (p < 0.05).

RESULTS: After a 5-year period, there was a significant decrease in all FD measures of the mandible in both T2DM and control groups (p < 0.05). This resulted in a statistical difference in the main effect of time. After a 5-year period, no significant difference in mandibular cortical measures was identified between the T2DM and control groups (p > 0.05).

CONCLUSION: According to panoramic radiography, the mandibular trabecular structure deteriorated after 5 years, whereas cortical values remained the same. It concluded that T2DM had no effect on these results.

PMID:37610653 | DOI:10.1007/s11282-023-00707-5

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PDGFRA, KIT, and KDR Gene Amplification in Glioblastoma: Heterogeneity and Clinical Significance

Neuromolecular Med. 2023 Aug 23. doi: 10.1007/s12017-023-08749-y. Online ahead of print.

ABSTRACT

Glioblastoma (GBM) is the most frequent tumor of the central nervous system, and its heterogeneity is a challenge in treatment. This study examined tumoral heterogeneity involving PDGFRA, KIT, and KDR gene amplification (GA) in 4q12 and its association with clinical parameters. Specimens from 22 GBM cases with GA for the 4q12 amplicon detected by FISH were investigated for homogeneous or heterogeneous coamplification patterns, diffuse or focal distribution of cells harboring GA throughout tumor sections, and pattern of clustering of fluorescence signals. Sixteen cases had homogenously amplification for all three genes (45.5%), for PDGFRA and KDR (22.7%), or only for PDGFRA (4.6%); six cases had heterogeneous GA patterns, with subpopulations including GA for all three genes and for two genes – PDGFRA and KDR (13.6%), or GA for all three and for only one gene – PDGFRA (9.1%) or KIT (4.6%). In 6 tumors (27.3%), GA was observed in focal tumor areas, while in the remaining 16 tumors (72.7%) it was diffusely distributed throughout the pathological specimen. Amplification was universally expressed as double minutes and homogenously stained regions. Coamplification of all three genes PDGFRA, KIT, and KDR, age ≥ 60 years, and total tumor resection were statistically associated with poor prognosis. FISH proved effective for detailed interpretation of molecular heterogeneity. The study uncovered an even more diverse range of amplification patterns involving the 4q12 oncogenes in GBM than previously described, thus highlighting a complex tumoral heterogeneity to be considered when devising more effective therapies.

PMID:37610648 | DOI:10.1007/s12017-023-08749-y

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Characterizing the Use of Exercise Testing in Repaired Tetralogy of Fallot Patients: A Multi-Institutional Survey

Pediatr Cardiol. 2023 Aug 23. doi: 10.1007/s00246-023-03269-9. Online ahead of print.

ABSTRACT

Cardiopulmonary exercise testing (CPET) is an important tool used in the management of patients with congenital heart disease. However, there are no clear guidelines for its use in specific populations, such as repaired Tetralogy of Fallot (rTOF). We sought to characterize current practice patterns and attitudes regarding exercise testing in the rTOF population using an online survey distributed to pediatric cardiologists. Analyses were performed using qualitative statistics, Wilcoxon rank-sum, Kruskal-Wallis test, and chi-squared analysis. 103 clinicians completed the survey with 83% routinely sending symptomatic rTOF patients for exercise testing and 59% for asymptomatic patients. Respondents who routinely test asymptomatic patients reported higher levels of perceived helpfulness of exercise testing (p < 0.01) and comfort with CPET interpretation (p < 0.01). Although a large majority of respondents found exercise testing to be helpful (81% either “somewhat” or “very” helpful”), a considerably smaller portion indicated comfort with CPET interpretation (49% either “comfortable” or “very comfortable”). Nearly all respondents (92%) reported changing management primarily based on exercise testing results. However, the frequency of changes varied, with 10% “frequently”, 62% “occasionally”, 19% “rarely” changing management. There was a statistically significant relationship between the perceived helpfulness of exercise testing and the likelihood of management changes (p < 0.01). While exercise testing is used to make clinical decisions, our findings suggest that in some cases, management changes may be made without a similar degree of confidence in interpreting CPET findings. The variability in attitudes and practices highlights the need for evidence-based guidelines addressing exercise testing in rTOF, particularly for asymptomatic patients.

PMID:37610637 | DOI:10.1007/s00246-023-03269-9

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Sex ratio of offspring is not statistically altered following pre-implantation genetic testing under a specific sex selection policy

Arch Gynecol Obstet. 2023 Aug 23. doi: 10.1007/s00404-023-07190-7. Online ahead of print.

ABSTRACT

PURPOSE: To determine whether the use of pre-implantation genetic testing (PGT) under a specific sex selection policy is associated with alterations in offspring sex ratio.

METHODS: This was a single-center retrospective cohort study of singleton live births from January 2018-December 2020 achieved via single blastocyst non-PGT or PGT frozen embryo transfer (FET). Per institutional policy, sex may be disclosed following PGT. If both sexes are available and morphologic grade is similar, patients may select the sex of the embryo to be transferred. Demographics and cycle characteristics were compared between non-PGT vs. PGT cycles with Mann-Whitney U or χ2. Poisson regression with robust variance estimates was used to model the probability of female vs. male offspring among non-PGT vs. PGT cycles, reported as risk ratio (RR) and 95% confidence interval (CI).

RESULTS(S): Among 541 live births, 350 (64.7%) were achieved with PGT and 191 (35.3%) without PGT. In both groups, female sex was more common, representing 59.4% of PGT-offspring and 55.0% of non-PGT offspring. After adjusting for potential confounders, the use of PGT was not significantly associated with an increased likelihood of female offspring (RR 1.04, 95% CI 0.98-1.11, p = 0.22).

CONCLUSION(S): Singletons born following FET had a higher rate of female sex than male. Allowing sex selection per institutional policy did not increase this ratio. These results contrast with those of prior publications and should motivate individual centers to monitor their own sex ratios. As utilization of PGT increases, local, regional, and national monitoring will become increasingly important.

PMID:37610634 | DOI:10.1007/s00404-023-07190-7

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The Role of BDNF and NPY Levels, Effects of Behavioral Systems and Emotion Regulation on Internet Addiction in Adolescents

Psychiatr Q. 2023 Aug 23. doi: 10.1007/s11126-023-10046-7. Online ahead of print.

ABSTRACT

Internet addiction (IA), one of the behavioral addictions, is also related to impulsivity. Although studies on its etiology and risks continue, the number of studies is limited. In this study, we aimed to assess the roles of behavioral systems, emotional regulation (ER), and impulsivity in the development of IA in adolescents and also to assess the relationship between all these clinical parameters and brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY). Forty-two adolescents with IA and 30 healthy controls (ages 12 -17) were included in the study. Self-reported measures included the Internet Addiction Scale. (IAS), Behavioral Activation and Behavioral Inhibition Scale (BAS/BIS), Barratt. Impulsiveness Scale-11 (BIS-11), and Difficulties in Emotion Regulation Scale-16 (DERS-16) were used for the assessment of the participants. The levels of plasma brain BDNF and NPY were evaluated with the ELISA method. BAS/BIS subscale scores, BIS-11, and DERS-16 scale total scores were found to be statistically significantly higher, while BDNF and NPY levels were found to be lower in adolescents with IA compared to the healthy controls. IA severity was not found to correlate with both BDNF and NPY. IA was found to be more related to BIS than to BAS. There is a need for further studies evaluating developmental features and possible diagnostic biomarkers that may be associated with IA in adolescents.

PMID:37610629 | DOI:10.1007/s11126-023-10046-7

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Features of patients and fracture risk in hypoparathyroidism; a single center study

J Endocrinol Invest. 2023 Aug 23. doi: 10.1007/s40618-023-02177-2. Online ahead of print.

ABSTRACT

PURPOSE: Patients with hypoparathyroidism (hypoPT) have low bone turnover and high bone mineral density (BMD). However, data on fracture risk are conflicting. The objectives of this study were: 1. To describe clinical/biochemical characteristics of hypoPT patients followed at a single medical center. 2. To identify postsurgical hypoPT patients and investigate their fracture rate compared with gender/age-matched post-surgical normocalcemic patients.

METHODS: Retrospective analysis of patient’s medical records treated at the tertiary medical center in 2010-2021 identified by computerized medical database search.

RESULTS: The cohort included 133 patients (91% women, mean age 64 ± 13 years) of whom 105 (79%) had post-thyroidectomy hypoparathyroidism and the remainder had an autoimmune/idiopathic/other etiology. Mean follow-up time was 21 ± 12 and 27 ± 12 years, respectively. The control group included 142 post-thyroidectomy patients without hypoparathyroidism. Patients in the postsurgical hypoparathyroidism group were older and had higher calcium and PTH levels at diagnosis than the non-surgical hypoPT patients. Comparing the postsurgical hypoPT and postsurgical normocalcemic control patients revealed a significantly higher BMD in the hypoPT group. Yet, fracture rates were 31% in the postsurgical hypoparathyroidism group and 21% in the control group (P = 0.1) over a similar median follow-up period (17 and 18.4 years, respectively). In both groups the most common fracture site was the spine (50% and 70%, respectively; p = 0.33), mainly nonclinical morphometric fractures. Higher phosphorus blood level was associated with increased fracture risk.

CONCLUSIONS: The relatively high BMD in patients with postsurgical hypoparathyroidism is not associated with lower fracture risk. Silent morphometric fractures are quite common in this group of patients.

PMID:37610611 | DOI:10.1007/s40618-023-02177-2

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Prothrombotic states in portal vein thrombosis and Budd-Chiari syndrome in India: A systematic review and meta-analysis

Indian J Gastroenterol. 2023 Aug 23. doi: 10.1007/s12664-023-01400-5. Online ahead of print.

ABSTRACT

BACKGROUND: Both Budd-Chiari syndrome (BCS) and portal vein thrombosis (PVT) have been linked to various prothrombotic (PT) conditions. The PT profile in Asians is different from the west and there are no nationwide epidemiological surveys from India. Hence, the present meta-analysis was aimed at analyzing the prevalence of acquired and hereditary thrombophilia among Indian patients with non-cirrhotic PVT and BCS.

METHODS: A comprehensive literature search of Embase, Medline and Scopus was conducted from January 2000 to February 2022 for studies evaluating the prevalence of various PT conditions in Indian patients with PVT and BCS. Pooled prevalence rates across studies were expressed with summative statistics.

RESULTS: Thirty-five studies with 1005 PVT patients and 1391 BCS patients were included in the meta-analysis. At least one PT condition was seen in 46.2% (28.7-63.7) of the PVT patients and 44.9% (37.3-60.7) of the BCS patients. Multiple PT conditions were seen in 13.0% (4.2-21.8) of the PVT patients and 7.9% (3.5-12.4) of the BCS patients. Among PVT patients, hyperhomocysteinemia was the commonest prothrombotic condition (21.6%) followed by protein C (PC) deficiency (10.7%), Janus kinase 2 (JAK-2) mutation (8.5%) and antiphospholipid antibodies (APLA) (7.5%). Among patients with BCS, PC deficiency was the commonest prothrombotic condition (10.6%) followed by methylenetetrahydrofolate reductase (MTHFR) mutation (9.8%), APLA (9.7%) and JAK-2 mutation (9.1%).

CONCLUSION: The PT profile in Indian patients with abdominal vein thrombosis is different from that of the western data with a lower prevalence of PT conditions in patients with BCS.

PMID:37610562 | DOI:10.1007/s12664-023-01400-5

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A survey of pediatric intensive care unit clinician experience with restricted family presence during COVID-19

Can J Anaesth. 2023 Aug 23. doi: 10.1007/s12630-023-02547-7. Online ahead of print.

ABSTRACT

PURPOSE: Limiting family presence runs counter to the family-centred values of Canadian pediatric intensive care units (PICUs). This study explores how implementing and enforcing COVID-19-related restricted family presence (RFP) policies impacted PICU clinicians nationally.

METHODS: We conducted a cross-sectional, online, self-administered survey of Canadian PICU clinicians to assess experience and opinions of restrictions, moral distress (Moral Distress Thermometer, range 0-10), and mental health impacts (Impact of Event Scale [IES], range 0-75 and attributable stress [five-point Likert scale]). For analysis, we used descriptive statistics, multivariate regression modelling, and a general inductive approach for free text.

RESULTS: Representing 17/19 Canadian PICUs, 368 of 388 respondents (94%) experienced RFP policies and were predominantly female (333/368, 91%), English speaking (338/368, 92%), and nurses (240/368, 65%). The mean (standard deviation [SD]) reported moral distress score was 4.5 (2.4) and was associated with perceived differential impact on families. The mean (SD) total IES score was 29.7 (10.5), suggesting moderate traumatic stress with 56% (176/317) reporting increased/significantly increased stress from restrictions related to separating families, denying access, and concern for family impacts. Incongruence between RFP policies/practices and PICU values was perceived by 66% of respondents (217/330). Most respondents (235/330, 71%) felt their opinions were not valued when implementing policies. Though respondents perceived that restrictions were implemented for the benefit of clinicians (252/332, 76%) and to protect families (236/315, 75%), 57% (188/332) disagreed that their RFP experience was mainly positive.

CONCLUSION: Pediatric intensive care unit-based RFP rules, largely designed and implemented without bedside clinician input, caused increased psychological burden for clinicians, characterized as moderate moral distress and trauma triggered by perceived impacts on families.

PMID:37610552 | DOI:10.1007/s12630-023-02547-7

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Mirikizumab Pharmacokinetics in Patients with Moderately to Severely Active Ulcerative Colitis: Results from Phase III LUCENT Studies

Clin Pharmacokinet. 2023 Aug 23. doi: 10.1007/s40262-023-01281-z. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Mirikizumab is a humanized anti-interleukin-23-p19 monoclonal antibody being developed for ulcerative colitis and Crohn’s disease. This analysis characterized mirikizumab pharmacokinetics using phase II and III trial data from patients with moderately to severely active ulcerative colitis.

METHODS: Serum pharmacokinetic data in patients receiving mirikizumab 50-1000 mg intravenously every 4 weeks as induction treatment and mirikizumab 200 mg subcutaneously every 4 or 12 weeks as maintenance treatment across three trials (N = 1362) were analyzed using non-linear mixed-effects modeling. Covariate effects on mirikizumab exposure were evaluated using simulation-based estimations.

RESULTS: Mirikizumab pharmacokinetics was best described by a linear two-compartment model with first-order absorption. Clearance, volume of distribution for central and peripheral compartments, and half-life were estimated at approximately 0.022 L/h (linear), 3.11 L and 1.69 L, and 9.5 days, respectively. Statistically significant effects of body weight and serum albumin levels on clearance, body weight on central and peripheral volumes of distribution, and body mass index on bioavailability were observed but effects were small relative to random inter-individual variability (% coefficient of variation: 18-64%). The subcutaneous bioavailability of mirikizumab was 48%.

CONCLUSIONS: Mirikizumab displayed pharmacokinetic characteristics typical of a monoclonal antibody where clearance increased with body weight and decreased with the albumin level, and bioavailability decreased with body mass index. These effects were small relative to random variability, indicating that a dose adjustment for patient factors is not required.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02589665 (28 October, 2015), NCT03518086 (8 May, 2018), NCT03524092 (14 May, 2018).

PMID:37610533 | DOI:10.1007/s40262-023-01281-z