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Female-biased association of NOS2-c.1823C>T (rs2297518) with co-susceptibility to metabolic syndrome and asthma

Can J Physiol Pharmacol. 2023 Jan 30. doi: 10.1139/cjpp-2022-0334. Online ahead of print.

ABSTRACT

The nitric oxide (NO) pathway contributes to the pathogeneses of metabolic syndrome (MetS) and asthma. NOS2 encodes inducible-NO synthase, which is an important enzyme of the pathway and its variations could affect the risk of asthma and MetS and thereby co-susceptibility to them. This study aimed to estimate the association of NOS2-c.1823C>T with risk of asthma, MetS, and asthma with MetS condition (ASMetS), and with asthma stages: intermittent, mild, moderate, and severe asthma. The study included asthmatics (n=555), MetS (n=334), and ASMetS cases (n=232) and 351 controls, which were genotyped by the PCR-RFLP method. The T allele was significantly associated with an increased risk of asthma and MetS in the sample population and females. CT genotype and CT+TT model were significantly associated with increased risk of ASMetS in females. A significant association between CT genotype and increased risk of ASMetS in the sample population and females was found in ASMetS vs. MetS. T allele significantly affects the risk of severe asthma in the sample population and females. The rs2297518 SNP of NOS2 contributes to the risk of MetS, asthma, and co-susceptibility to them, and this contribution may be stronger in females compared to males.

PMID:36716438 | DOI:10.1139/cjpp-2022-0334

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Colorectal and Bladder Prokinetic Activity of [Lys5,MeLeu9,Nle10]-NKA(4-10) after Intranasal or Sublingual Delivery in Dogs

Can J Physiol Pharmacol. 2023 Jan 30. doi: 10.1139/cjpp-2022-0498. Online ahead of print.

ABSTRACT

The feasibility of eliciting defecation and urination after intranasal (IN) or sublingual (SL) delivery of a small peptide NK2 receptor agonist, [Lys5,MeLeu9,Nle10]-NKA(4-10) (LMN-NKA), was examined using prototype formulations in dogs. In anesthetized animals, administration of 100 or 300 μg/kg IN or 2.0-6.7 mg/kg SL increased colorectal peak pressure and area under the curve (AUC). Peak bladder pressure was also increased at the same doses, and this was accompanied by highly efficient voiding at normal physiological bladder pressures. The onset of these effects was rapid (<2.5 min), and the primary contractions lasted ~25 min, returning to baseline in <60 min. Slight hypotension lasting a few minutes and causing <10% change from baseline was detected after higher doses and was statistically significant after only 100 μg/kg IN. In conscious dogs, there was a dose-related increase in voiding responses and reduction in the latency to urinate and defecate after 300 and 1,000 μg/kg IN; emesis was also observed at these doses. SL administration of 6.7 mg/kg induced urination within 10 min, but not defecation or emesis. These findings support the feasibility of developing a convenient dosage form of small peptide NK2 receptor agonists as on-demand defecation or urination therapies.

PMID:36716436 | DOI:10.1139/cjpp-2022-0498

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Improved Margin Control of Microcystic Adnexal Carcinoma After Mohs Micrographic Surgery Compared With Wide Local Excision

Dermatol Surg. 2023 Jan 27. doi: 10.1097/DSS.0000000000003705. Online ahead of print.

ABSTRACT

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a locally aggressive and deeply infiltrative cutaneous tumor primarily treated with excision; however, there are limited data comparing outcomes by surgical approach.

OBJECTIVE: To compare surgical outcomes of MAC treated with Mohs micrographic surgery (MMS) and wide local excision (WLE).

METHODS: A 27-year retrospective cohort study of primary MAC was performed. Surgical (i.e. margin status after resection) and recurrence outcomes (including local recurrence [LR], nodal metastases [NM], and distance metastases [DM]) were analyzed by type of surgical approach (MMS and WLE).

RESULTS: Sixty-nine MACs were included, of which 34 (49.3%) were treated with MMS and 35 (50.7%) with WLE. All MMS-treated tumors had negative margins after the first surgery attempt. Twenty-one (60.0%) tumors treated with WLE had positive margins after the first surgical attempt and required additional procedures. More tumors treated with WLE developed LR, NM, or DM, although this did not meet statistical significance.

LIMITATIONS: Retrospective single institution study.

CONCLUSION: Greater than half of MAC tumors treated with WLE had positive margins after the initial surgery and required multiple procedures for complete removal. Real-time complete margin assessment is important for this locally aggressive and infiltrative tumor.

PMID:36716422 | DOI:10.1097/DSS.0000000000003705

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Intraobserver and Interobserver Consistency Evaluation of Carotid Plaque Volume Measured by Different 3-Dimensional Ultrasound Methods

Ultrasound Q. 2023 Jan 26. doi: 10.1097/RUQ.0000000000000635. Online ahead of print.

ABSTRACT

This study aims to evaluate the accuracy of the semiautomatic planimetric measurement (SAPM) method and the necessity of manually adjusted boundary measurement in 3-dimensional ultrasound measurement of plaque volume. A total of 50 patients with 82 plaques in the common carotid arteries between December 2020 and March 2021 were included in this study. Two observers measured the 3-dimensional volume of plaque for each patient in 3 different methods (contour tracing method [CTM], SAPM method without manually adjusted boundary [SAPM1], and SAPM method with manually adjusted boundary [SAPM2]). The difference in measurement time between the 3 methods was evaluated by Kruskal-Wallis H test. Intraclass correlation coefficient and 95% confidence interval were used to evaluate the intraobserver and interobserver reliability of the 3 measurement modes. The Bland-Altman analysis was used to assess the agreement, which was expressed as the mean difference with the 95% limits of agreement (LOA). The difference in measurement time between the 3 methods was statistically significant (P < 0.001). Both observers’ intraobserver and interobserver reliability showed well in the 3 methods (all of the intraclass correlation coefficients were >0.75). The mean differences of the plaque volume measurement were 38.17, 26.42, and 11.75 mm3, respectively. The agreement between CTM and SAPM2 was the best, and LOA was -57.00 to 80.51. The agreement between SAPM1 and SAPM2 and the agreement between SAPM1 and CTM were similar, and the LOAs were -126.10 to 202.40 and -158.00 to 210.80, respectively. The SAPM method may be recommended to measure plaque volume in clinical practice.

PMID:36716417 | DOI:10.1097/RUQ.0000000000000635

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The Impact of Donor Preparation for Tissue Procurement on Postmortem Vitreous Isopropanol Concentration

Am J Forensic Med Pathol. 2023 Jan 25. doi: 10.1097/PAF.0000000000000810. Online ahead of print.

ABSTRACT

Volatile chemicals can be relevant in the determination of the cause and manner of death by forensic pathologists. Isopropanol is a secondary alcohol that is occasionally seen on postmortem toxicology testing. A series of 11 forensic autopsy cases was previously reported in which the presence of isopropanol in the vitreous humor was suspected to be due to postmortem contamination from the body preparation process for tissue procurement.In collaboration with a tissue procurement agency, donor vitreous humor was collected from one eye before body preparation for procurement and from the other eye postpreparation. The specimens underwent testing for volatile substances by headspace gas chromatography.Of the 50 cases, 8 (16%) showed statistically significant changes in the prepreparation and postpreparation isopropanol concentrations. Postpreparation isopropanol concentrations ranged from 5 to 104 mg/dL (median, 18 mg/dL). Seven of the 8 cases had undetectable prepreparation isopropanol, whereas the remaining case had a detectable prepreparation isopropanol.In conclusion, surface contamination of the decedent’s body with chemicals used in body preparation can lead to the passive absorption into the body, resulting in the presence of isopropanol in postmortem toxicology samples. Forensic pathologists need to be aware of this when interpreting postmortem samples after tissue procurement.

PMID:36716410 | DOI:10.1097/PAF.0000000000000810

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Cremation Permit Review and COVID-19 Death Certificates

Am J Forensic Med Pathol. 2023 Jan 27. doi: 10.1097/PAF.0000000000000814. Online ahead of print.

ABSTRACT

Data derived from death certificates (DCs) is an important resource for mortality statistics, disease surveillance, and the creation of public health policies. This study involved the review of COVID-19 DCs occurring during the normal course of DC review for cremation approval purposes in a medical examiner office. During the review process since the occurrence of the pandemic, it was noticed that a significant percentage of COVID-19 DCs being reviewed did not include any comorbid conditions as contributing to death, despite reports, both within the medical literature and within the media, that suggested that most deaths occur in people with known risk factors. The study involved medical record review for COVID-19 DCs that did not list any comorbid conditions. The results indicated that a vast majority of such cases did, in fact, have significant comorbid conditions, such that they should have been listed on the DCs.

PMID:36716405 | DOI:10.1097/PAF.0000000000000814

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Efficacy of Anal Sphincter Division During Fistulotomy in Anal Fissure Associated Fistula

Dis Colon Rectum. 2023 Jan 24. doi: 10.1097/DCR.0000000000002700. Online ahead of print.

ABSTRACT

BACKGROUND: A subset of chronic anal fissures beget focal infection, leading to concomitant fistula. The optimal management of fissure associated fistula is unknown.

OBJECTIVE: We sought to characterize healing rates and effect of fistulotomy in fissure associated fistula.

DESIGN: Retrospective study.

SETTING: Urban tertiary center.

PATIENTS: Adults who underwent fistulotomy for a fistula associated with a chronic anal fissure. Crohn’s disease, history of lateral internal sphincterotomy, and fistula not amenable to fistulotomy were excluded.

INTERVENTIONS: Patients were managed with fistulotomy. Fissures were otherwise managed conservatively with a step-up approach.

MAIN OUTCOME MEASURES: The primary endpoint was healing, defined as resolution of symptoms and both fistula and fissure wounds within one year. Subgroup analysis compared those who underwent subcutaneous fistulotomy (group A) versus fistulotomy involving anal sphincter fibers (group B).

RESULTS: Twenty-four of 38 patients (63%) patients healed with a median overall follow-up of 6.6 months (4.2-14.1). The overall median time to healing was 4.4 months (2.2-6.0). No clinical or pathologic factors predicted healing. In subgroup analysis, overall subcutaneous fistulotomy healing rates were non-statically lower at 46% (6/13) compared to fistulotomy involving anal sphincter fibers at 72%, (18/25; p = 0.16). There was no difference in time to healing [Subcutaneous fistulotomy 6.7 months (5.2-8.4) vs. Fistulotomy involving sphincter 5.1 months (2.1-7.0); p = 0.36].

LIMITATIONS: Treatment bias, with increased utilization of chemical sphincter relaxing agents in those who did not heal. Not applicable to complex fistulas, Crohn’s disease, or atypical fissures.

CONCLUSIONS: Patients presenting with chronic fissure and associated subcutaneous, intersphincteric, or low transphincteric fistula are successfully managed with fistulotomy. Patients with a subcutaneous fistula tract exhibited non-statistically significant lower rates of healing. See Video Abstract at http://links.lww.com/DCR/C145.

PMID:36716394 | DOI:10.1097/DCR.0000000000002700

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Effect of Capsaicin Atomization on Cough and Swallowing Function in Patients With Hemorrhagic Stroke: A Randomized Controlled Trial

J Speech Lang Hear Res. 2023 Jan 30:1-10. doi: 10.1044/2022_JSLHR-22-00296. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with hemorrhagic stroke have high mortality and disability rates. Nevertheless, early rehabilitation interventions can improve their outcomes. We aimed to apply capsaicin atomization as early intervention to patients with hemorrhagic stroke and explore improvements in cough and swallowing functions.

METHOD: Patients with hemorrhagic stroke were randomly divided into the control group, which received routine care, and the intervention group, which underwent the capsaicin solution nebulization scheme in addition to routine care. Differences in the presence/absence of cough reflex and number of coughs in response to capsaicin, the presence/absence of swallowing reflex in response to water, the presence/absence of postswallow residue, substance P (SP) concentration, and pulmonary inflammation between the two groups were determined before and after the intervention.

RESULTS: A total of 53 patients with hemorrhagic stroke were included. Results showed no statistically significant difference in cough reflex in both groups after the intervention (p > .05). The degree of cough in the intervention group was stronger than that in the control group (p = .046). No statistically significant difference was observed in the number of patients with swallowing reflex in response to water between the groups (p > .05). The presence/absence of postswallow residue of the intervention group was stronger than that of the control group (p = .032). No statistically significant difference was observed between the Glasgow Coma Scale scores of the groups after the intervention (p > .05). SP in the intervention group was significantly increased (p = .031). The Clinical Pulmonary Infection Score was significantly lower in the control group, and the difference was statistically significant (p = .028).

CONCLUSIONS: Capsaicin nebulization can help enhance the number of coughs in response to capsaicin, reduce postswallow residue, and increase the level of SP in patients with hemorrhagic stroke and has a positive effect on pulmonary inflammation. This study provides intervention points for cough and swallowing rehabilitation after a hemorrhagic stroke.

SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.21956903.

PMID:36716393 | DOI:10.1044/2022_JSLHR-22-00296

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Patient Reported Outcomes Following Anterior and Posterior Surgical Approaches for Multilevel Cervical Myelopathy

Spine (Phila Pa 1976). 2023 Jan 30. doi: 10.1097/BRS.0000000000004586. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective Cohort.

OBJECTIVE: To compare health related quality of life (HRQoL) outcomes between approach techniques for the treatment of multilevel degenerative cervical myelopathy (DCM).

SUMMARY OF BACKGROUND DATA: Both anterior and posterior approaches for the surgical treatment of cervical myelopathy are successful techniques in the treatment of myelopathy. However, the optimal treatment has yet to be determined, especially for multilevel disease, as the different approaches have separate complication profiles and potentially different impacts on HRQoL metrics.

METHODS: Retrospective review of a prospectively managed single institution database of patient reported outcome measures following three- and four-level anterior cervical discectomy and fusion (ACDF) and posterior cervical decompression and fusion (PCDF) for DCM. The electronic medical record was reviewed for patient baseline characteristics and surgical outcomes while preoperative radiographs were analyzed for baseline cervical lordosis and sagittal balance. Univariate and multivariate statistical analyses were performed to compare the two groups.

RESULTS: We identified 153 patients treated by ACDF and 43 patients treated by PCDF. Patients in the ACDF cohort were younger (60.1±9.8 vs. 65.8±6.9 y, P<0.001), had a lower overall comorbidity burden (CCI: 2.25±1.61 vs. 3.07±1.64, P=0.002), and were more likely to have a three-level fusion (79.7% vs. 30.2%, P<0.001), myeloradiculopathy (42.5% vs. 23.3%, P=0.034), and cervical kyphosis (25.7% vs. 7.69%, P=0.027). Patients undergoing an ACDF had significantly more improvement in their neck disability index (NDI) after surgery (-14.28 vs. -3.02, P=0.001), and this relationship was maintained on multivariate analysis with PCDF being independently associated with a worse NDI (+8.83, P=0.025). Patients undergoing an ACDF also experienced more improvement in visual analog score neck pain after surgery (-2.94 vs. -1.47, P=0.025) by univariate analysis.

CONCLUSION: Patients receiving an ACDF for multilevel DCM may experience a HRQoL improvement compared to those receiving a PCDF.

PMID:36716386 | DOI:10.1097/BRS.0000000000004586

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Evaluating treatment response to mepolizumab in patients with severe CRSwNP

Rhinology. 2023 Jan 30. doi: 10.4193/Rhin22.200. Online ahead of print.

ABSTRACT

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.

PMID:36716382 | DOI:10.4193/Rhin22.200