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Cytoplasmic WT1 in IgA nephropathy, an indicator of poor prognosis associated with mesangial/peri-mesangial C4d

Int Urol Nephrol. 2022 Aug 29. doi: 10.1007/s11255-022-03357-4. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to investigate the immuno-histochemical expression of C4d, ADAM10 and WT1 in kidney biopsies of immunoglobulin A nephropathy (IgAN) patients and correlate the findings with clinical, laboratory and histopathologic features in the hope of defining new parameters to better understand the pathogenesis of the disease, and predict prognosis.

MATERIALS AND METHODS: Paraffin-embedded kidney biopsy samples of 128 IgAN patients were immuno-histochemically treated with C4d and ADAM10/WT1 dual stain. Results were evaluated according to Oxford classification parameters, epidemiologic features, laboratory findings at presentation and clinical follow-up.

RESULTS: We observed C4d positivity in 40.6% of our patients, 25% of which was mesangial/peri-mesangial (m/pm) staining. Only m/pmC4d positivity statistically correlated with progression to end-stage renal disease (ESRD). M/pmC4d positive patients had statistically significantly higher baseline proteinuria levels, presence of crescents and > 25% segmental sclerosis of glomeruli. There was cytoplasmic staining of WT1 in 11.2% of cases. Presence of cWT1 correlated with m/pmC4d positivity and progression to ESRD. There was no glomerular ADAM10 detected and tubular expression of this protein did not relate to amount of tubular damage or other parameters.

CONCLUSION: This study is the first to show that cWT1is involved in IgAN and appears as an independent variable for worse prognosis.

PMID:36036855 | DOI:10.1007/s11255-022-03357-4

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The Fibromyalgia Transcutaneous Electrical Nerve Stimulation in Physical Therapy Study (FM-TIPS) Protocol: A Multisite Embedded Pragmatic Trial

Phys Ther. 2022 Aug 29:pzac116. doi: 10.1093/ptj/pzac116. Online ahead of print.

ABSTRACT

OBJECTIVES: Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that provides an electrical current through the skin to produce analgesia. The primary purpose of this study is to examine if the addition of TENS to routine physical therapy improves movement-evoked pain in individuals with fibromyalgia in a physical therapy clinical setting.

METHODS: FM-TIPS is a phase III embedded pragmatic clinical trial funded through the National Institutes of Health Helping to End Addiction Long-Term (HEAL) Initiative. This trial will utilize a randomized cluster design that includes more than 110 physical therapists in 24 to 30 physical therapy clinics within 6 health care systems and 7 states. Clinics will be randomized to TENS or No-TENS, stratified by health care system and clinic size. The plan is to enroll 600 participants, with all participants completing physical therapy as prescribed by their physical therapist. Participants at TENS clinics will utilize TENS for a minimum of 2-hour per day while at the physical therapy clinic and at home when active. The primary outcome is reduction in movement-evoked pain from baseline to Day 60 on an 11-point numeric rating scale when participants sit and stand five times (Sit and Stand Test) Secondary outcomes include resting pain and fatigue, pain interference, fibromyalgia disease activity, movement-evoked fatigue, multidimensional assessment of fatigue, rapid assessment of physical activity, patient global impression of change, and common data elements shared across studies supported through the HEAL Initiative.

PMID:36036838 | DOI:10.1093/ptj/pzac116

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Association between prehospital FPS and ROSC in adults with OHCA : A retrospective multicenter study using the German Resuscitation Registry and Intubation Registry (FiPS-CPR)

Anaesthesiologie. 2022 Aug 29. doi: 10.1007/s00101-022-01193-w. Online ahead of print.

ABSTRACT

BACKGROUND: Advanced airway management (AAM) is part of the standard treatment during advanced cardiac life support (ACLS). Current studies underline the importance of a first-pass intubation success (FPS) during in-hospital ACLS. It was shown that a failed initial intubation attempt in out-of-hospital cardiac arrest (OHCA) patients in the emergency department is an independent risk factor for the decreased effectiveness of ACLS measured by the return of spontaneous circulation (ROSC).

OBJECTIVE: This study first examines the association between prehospital FPS and ROSC in adults with OHCA and second identifies factors associated with FPS and ROSC. The initial hypothesis was that FPS would increase the probability of ROSC as well as decrease the time to ROSC.

MATERIAL AND METHODS: A retrospective multicenter analysis of 180 adult non-traumatic OHCA patients on whom advanced airway management (AAM) was performed between July 2017 and December 2018 in five different German physician-staffed ambulance stations. For information on FPS the Intubation Registry, and for information on ROSC the German Resuscitation Registry were used. In addition to yes/no questions, multiple answers and free text answers are possible in those questionnaires. The main outcome variables were ‘FPS’, ‘ROSC’ and ‘time to ROSC’. Mann-Whitney tests, χ2-tests, Fisher’s exact tests and multivariate binary logistic regressions were used for the statistical evaluation. Demographic factors, characteristics of the performer, selected equipment, laryngoscopy type, intubation method, medications, verification of tube position, respiratory evaluation, complications and time to ROSC were examined with respect to the influence on FPS. Concerning ROSC, the following factors were examined: demographic factors, initial heart rhythm, initial breathing, medications, defibrillation and AAM.

RESULTS: An FPS was recorded in 150 patients (83.3%), and ROSC was achieved in 82 patients (45.5%) after an average time of 22.16 min. There was a positive association between FPS and ROSC (p = 0.027). In patients with FPS, a trend for shorter time to ROSC was observed (p = 0.059; FPS 18 min; no FPS 28 min). The use of capnography (odds ratio, OR = 7.384, 95% confidence interval, CI 1.886-28.917) and complications during AAM (OR = 0.033, 95% CI: 0.007-0.153) were independently associated with FPS. The independent factor associated with ROSC was FPS (OR = 5.281, 95% CI: 1.800-15.494).

CONCLUSION: In prehospitally resuscitated adult OHCA patients with AAM, FPS is associated with a higher chance of ROSC.

PMID:36036834 | DOI:10.1007/s00101-022-01193-w

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Impact of rs11024102 PLEKHA7, rs3753841 COL11A1 single nucleotide polymorphisms, and serum levels of oxidative stress markers on the risk of primary angle-closure glaucoma in Egyptians

J Genet Eng Biotechnol. 2022 Aug 29;20(1):126. doi: 10.1186/s43141-022-00400-w.

ABSTRACT

BACKGROUND: Primary angle-closure glaucoma (PACG) is one of the major causes of blindness in the Middle East with genetic loci and systemic oxidative stress as potential risk factors. The current case-control study aimed to investigate the associations of rs11024102 in Pleckstrin homology domain-containing family A member 7 (PLEKHA7), rs3753841 in collagen 11 A1 (COL11A1), and the systemic oxidative stress markers with PACG in Egyptian patients. Thirty-five control subjects and 64 PACG patients were enrolled in this study. The polymorphisms in PLEKHA7 and COL11A1 were analyzed using quantitative PCR, and their associations were statistically tested with PACG at homozygous, heterozygous, dominant, and recessive genetic models. The levels of malondialdehyde (MDA), advanced glycation-end product (AOPP), protein carbonyl (PC), and ischemia modified albumin (IMA) were quantitated colorimetrically, and their associations with PACG were analyzed statistically. The associations of MDA, AOPP, PC, and IMA with elevated intraocular pressure (IOP) were statistically tested.

RESULTS: Neither significant difference in the genotype distribution nor allele frequency of PLEKHA7 11024102 T>C (p = 0.425 and 0.517, respectively) and COL11A1 rs3753841 G>A (p = 0.600 and 0.473, respectively) were recorded under any of the tested genetic models. Either rs11024102 PLEKHA7 or rs3753841 COL11A1 was not significantly (p > 0.025 after Bonferroni correction) associated with an increased risk of PACG in Egyptians. Egyptian patients with PACG showed significant elevations in the serum levels of MDA, AOPP, and PC either in patients with or without cases with diabetes mellites, hypertension, coronary vascular diseases, and smoking. Serum levels of MDA, AOPP, and PC were significantly associated with PACG in Egyptians (p < 0.013 after Bonferroni correction). However, MDA and PC only showed significant associations with the elevation in the IOP (p = 0.007 and 0.045, respectively) in PACG patients.

CONCLUSION: Both rs11024102 and rs3753841 could not be considered as potential gene-dependent risk factors for PACG pathogenesis in Egyptians. On the other hand, serum levels of MDA, AOPP, and PC might be considered risk factors for PACG. Moreover, MDA and PC could serve as good predictors for the elevation of the IOP in PACG disease.

PMID:36036827 | DOI:10.1186/s43141-022-00400-w

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Predictors of low and high opioid tablet consumption after inguinal hernia repair: an ACHQC opioid reduction task force analysis

Hernia. 2022 Aug 29. doi: 10.1007/s10029-022-02661-3. Online ahead of print.

ABSTRACT

PURPOSE: Prescribing and consumption of opioids remain highly variable. Using a national hernia registry, we aimed to identify patient and surgery specific factors associated with low and high opioid tablet consumption after inguinal hernia repair.

METHODS: This was a retrospective cross-sectional study evaluating patients undergoing elective inguinal hernia repair with 30-day follow-up and patient-reported opioid consumption from March 2019 to March 2021 using the Abdominal Core Health Quality Collaborative. Clinically significant patient demographics, comorbidities, operative details, quality-of-life measurements, and surgeon prescribing data were entered into a multivariable logistic regression model to identify statistically significant predictors of patients who took no opioid tablets or >10 tablets.

RESULTS: A total of 1937 patients were analyzed. Operations included 59% laparoscopic or robotic, 35% open mesh, and 6% open non-mesh repairs. Of these patients, 50% reported taking zero, 42% took 1-10, and 8% took ≥10 opioid tablets at 30-day follow-up. Patients who were older (OR 1.55, 95% CI 1.34-1.79, p-value <0.001), ASA ≤ 2 (OR 1.56, 95% CI 1.2-2.01, p-value <0.001), had no preoperative opioid use at baseline (OR 2.29, 95% CI 1.31-4.03, p-value = 0.004), had local anesthetic with general anesthesia (OR 1.39, 95% CI 1.0.5-1.85, p-value = 0.022), or prescribed <7 opioid tablets (OR 2.27, 95% CI 1.96-2.62, p-value <0.001) were more likely to take no opioid tablets.

CONCLUSION: Older, healthier, opioid naïve patients with local anesthetic administered during elective inguinal hernia repair are most likely to not require opioids. Surgeon prescribing-arguably the most modifiable factor-independently correlates with both low and high opioid consumption.

PMID:36036822 | DOI:10.1007/s10029-022-02661-3

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Acute clavicle fixation after blunt chest trauma: effect on pulmonary outcomes and patient disposition

Eur J Orthop Surg Traumatol. 2022 Aug 29. doi: 10.1007/s00590-022-03368-y. Online ahead of print.

ABSTRACT

PURPOSE: Clavicle fractures are common in patients who sustain blunt chest trauma (BCT). Recently, surgical fixation of rib fractures in patients with BCT has been shown to improve pulmonary and clinical outcomes. Therefore, the purpose of this study is to assess the role of early clavicle fixation (ECF) versus non-operative (NO) treatment for midshaft clavicle fractures in this same population.

METHODS: A retrospective chart review was performed in patients with midshaft clavicle fractures and BCT at a Level I Trauma Center between 2007 and 2017. Patients with pre-existing pulmonary conditions and head injuries necessitating mechanical ventilation were excluded. Demographic data, injury mechanisms, and Thoracic Trauma Severity Scores (TTS) were analyzed. Inpatient pulmonary outcomes were assessed with serial vital capacity (VC) measurements, intubation, mechanical ventilation, and pulmonary complications data. In addition, intensive care unit (ICU) and hospital length of stay (LOS), mortality, discharge location, and incidence of postoperative complications in the ECF group were also measured.

RESULTS: Thirty-six patients underwent ECF, and 24 underwent NO treatment. The ECF cohort was statistically younger and had a greater incidence of clavicle fracture shortening than the NO group. There was no difference in pulmonary outcomes, ICU or hospital LOS, or mortality between groups. There were no complications associated with ECF. Patients who underwent ECF were more likely to discharge to home. There were no postoperative complications associated with ECF.

CONCLUSION: ECF of midshaft clavicle fractures does not improve pulmonary outcomes in patients with BCT. However, despite the lack of pulmonary benefit, there appears to be no added risk of harm. Therefore, ECF is a reasonable consideration in this patient population who otherwise meet clavicle fracture operative indications.

PMID:36036820 | DOI:10.1007/s00590-022-03368-y

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Nurses’ Awareness and Practices of Unintentional Perioperative Hypothermia Prevention, A Cross-Sectional Study

Ther Hypothermia Temp Manag. 2022 Aug 25. doi: 10.1089/ther.2022.0030. Online ahead of print.

ABSTRACT

Unintentional perioperative hypothermia can cause potentially life-threatening complications. The aim of this study was to determine the awareness and practices of nurses regarding unintentional perioperative hypothermia prevention. The study was conducted at a teaching hospital in Gambia with descriptive cross-sectional design. A total of 53 nurses voluntarily participated in this study. The questionnaire used in this study was developed based on the American periOperative Registered Nurses (AORN) and National Institute for Health and Care Excellence perioperative hypothermia guidelines. Descriptive statistics, Pearson correlation, Student t-test, and one-way ANOVA were used in the analysis of data. The result of the study showed that nurses had high level of awareness of unintentional perioperative hypothermia prevention; however, practice levels were found to be low. Based on the results of the study, development of policies, implementation of the unintentional perioperative hypothermia prevention guidelines, and continuous education to improve nurses’ knowledge and practices were recommended.

PMID:36036803 | DOI:10.1089/ther.2022.0030

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Evaluation of Liver Stiffness Measurement Based Scores in Liver Transplant Recipients

Liver Transpl. 2022 Aug 29. doi: 10.1002/lt.26568. Online ahead of print.

ABSTRACT

Combining bio-clinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplant (LT) recipients. Thus, the aim of the current study was to evaluate the diagnostic performance of combining LSM-based scores to LSM alone for detection of advanced fibrosis in LT recipients.

METHOD: Adult LT recipients with a liver biopsy, VCTE and clinical data necessary to construct LSM-based fibrosis models (FAST, Agile 3+ and Agile 4) were included (N=132). The diagnostic statistics advanced fibrosis [fibrosis stage 0-2 vs. 3-4] were determined using optimal cut-off using Youden index.

RESULTS: The area under the receiver operator curve (AUROC) [95% CI] for LSM was 0.94 [0.89, 0.99], FAST was 0.65 [0.50, 0.79], Agile 3+ was 0.90 [0.83, 0.97], and Agile 4 was 0.90 [0.83, 0.97]. No statistically significant differences were noted between the AUROC of LSM vs. LSM-based scores. The false positive rates for Agile 3+ and Agile 4 was 14.5% and 11.8% compared to 8.3% for LSM alone. The false positive rates in LSM-based scores were higher among patients with diabetes, higher AST levels and lower platelet counts.

CONCLUSION: The LSM based scores do not improve the diagnostic performance of LSM alone in LT recipients for detection of advanced fibrosis. This results from the impact of immunosuppression on bio-clinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.

PMID:36036790 | DOI:10.1002/lt.26568

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The diagnostic importance of multiple cytokines in adult hemophagocytic lymphohistiocytosis

J Clin Lab Anal. 2022 Aug 29:e24669. doi: 10.1002/jcla.24669. Online ahead of print.

ABSTRACT

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a category of immunological illnesses that cause out-of-control T cells and macrophages to release life-threatening cytokines. The HLH-2004 diagnostic criteria are the gold standard for HLH diagnosis, but there is a need to investigate the usefulness of various cytokines for HLH diagnosis.

METHODS: Patients admitted to Beijing Friendship Hospital of Capital Medical University from January 2016 to December 2020 were included in this retrospective study, with 166 patients with confirmed HLH and 142 febrile patients requiring differential diagnosis completing the sum. Multiplex cytokine assays using multifactor liquid phase microarray technology-based multifactor liquid phase microarray technology were used to detect 33 cytokines. Twenty-eight cytokines detected using the Luminex analytical platform technology were ultimately included in the analysis.

RESULTS: Interleukin-1 receptor antagonist (IL-1 RA), IL-18, interferon-γ (IFN-γ), and interferon-induced protein 10 (IP-10) regulated upon activation normal T cell expressed and secreted (RANTES), eotaxin, growth-related oncogene α (GRO-α), and macrophage inflammatory protein-1 α (MIP-1α) were higher in the HLH group than in the non-HLH group, and the differences were statistically significant. Among them, the area under the curve (AUC) for IL-18 for HLH diagnosis was reported for the first time as 82.69%, with a sensitivity of 76.32% and a specificity of 79.61%; the AUC of IL-1 RA was 72.34%, with a sensitivity of 62.71% and a specificity of 75.97%; and the AUC of IP-10 was 71.73%, with a sensitivity of 60.14% and a specificity of 75.15%. Moreover, the AUC of the combined diagnostic tests for IL-1 RA, IL-18, IFN-γ, IP-10, and RANTES was 99.6%, with a sensitivity of 95.8% and a specificity of 98.6%.

CONCLUSION: Our study concluded that multiple cytokines are valid biological markers for the diagnosis of HLH. The findings of this study remain to be validated in an external dataset.

PMID:36036769 | DOI:10.1002/jcla.24669

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Gesture-speech integration is related to vocabulary skills in children with developmental language disorder, Williams syndrome and typical development

Int J Lang Commun Disord. 2022 Aug 29. doi: 10.1111/1460-6984.12780. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals with developmental language disorder or Williams syndrome are reported to use more gestures than individuals with typical development. However, these two groups differ considerably in visuospatial and language skills, two skills that are hypothesized to shape gesture rate.

AIMS: We first examined whether children with both developmental language disorder and children Williams syndrome do indeed use more gestures. Our second aim was to disentangle the role of vocabulary and visuospatial skills in the use of supplementary gestures (i.e., containing unique information). To account for participant heterogeneity, analyses included both group comparisons and vocabulary and visuospatial skills at an individual level. As a third aim, the role of visuospatial skills was further examined in relation to gestures containing spatial content.

METHODS & PROCEDURES: In a cross-sectional group design, three participant groups watched and then retold a cartoon: children with typical development (n = 25), children with developmental language disorder (n = 25) and children/young people with Williams syndrome (n = 14). Their narrations were transcribed and hand gestures were coded based on gesture-speech integration (redundant, adds information to particular lexical items, gives information that is entirely absent from speech) and spatial content. Participants’ expressive vocabulary and visuospatial skills were measured.

OUTCOMES & RESULTS: Between-group comparisons showed that individuals with developmental language disorder or Williams syndrome did indeed use more gestures. Poisson loglinear modelling demonstrated that a relative higher use of supplementary gestures was determined by lower expressive vocabulary skills. Neither the group distinction nor visuospatial skills shaped the supplementary gesture rate nor spatial gesture rate.

CONCLUSIONS & IMPLICATIONS: Regardless of neurodevelopmental condition or typical development, a higher use of supplementary gestures was influenced by expressive vocabulary skills. Children with lower vocabulary skills spontaneously capitalized on the multimodality of communication to express constituents that were not present in their verbal speech. This finding is a promising starting point for future gesture intervention studies examining whether implicit modelling of gesture use can encourage gestures even more in these children and if this allows them to achieve higher linguistic complexity. On a methodological note, the observed intra-group skill variability demonstrates that group comparisons need to be complemented with correlational measures accounting for skills at an individual level.

WHAT THIS PAPER ADDS: What is already known on the subject Children with developmental language disorder and children with Williams syndrome are more inclined to use gestures than typically developing children. Research conducted in adults with typical development points towards the role of lexical and visuospatial skills in gesture use, but it is unclear how these skills shape gesture use in children with atypical development. What this paper adds to existing knowledge This study compares the rate of gestures that convey meaning that is not expressed in speech between the three aforementioned populations. Novel is the inclusion of the group distinction, individual lexical skills, and visuospatial skills in one encompassing statistical model. What are the potential or actual clinical implications of this work? The inclination to use gestures that replace speech is related to lexical skills. Visuospatial skills do not seem to play a role and should not be considered as a factor when thinking about gesture intervention. Understanding how gestures relate to specific skills is a first step to understanding how gesture interventions can bolster language production.

PMID:36036738 | DOI:10.1111/1460-6984.12780