Category: Nevin Manimala

Eur J Clin Invest. 2022 Apr 13:e13792. doi: 10.1111/eci.13792. Online ahead of print.

ABSTRACT

Increased production of reactive oxygen species (ROS) and oxidative stress are known to play a key role in the pathogenesis of type 2 diabetes (T2D), however, the relationship between genes encoding a multi-subunit ROS-generated enzyme NADPH oxidase and disease susceptibility remains unexplored. The present pilot study investigated whether single nucleotide polymorphisms (SNP) at the RAC1 gene (Rac family small GTPase 1), a molecular switcher of NADPH oxidase, are associated with the risk of T2D, glucose metabolism, and redox homeostasis. DNA samples from 3206 unrelated Russian subjects (1579 T2D patients and 1627 controls) were genotyped for six common SNPs rs4724800, rs7784465, rs10951982, rs10238136, rs836478, and rs9374 of RAC1 using the MassArray-4 system. SNP rs7784465 was associated with an increased risk of T2D (P=0.0003) and significant differences in the RAC1 haplotypes occurred between the cases and controls (P=0.005). Seventeen combinations of RAC1 genotypes showed significant associations with T2D risk (FDR<0.05). Associations of RAC1 polymorphisms with T2D were modified by environmental factors such as sedentary lifestyle, psychological stresses, a dietary deficit of fresh fruits/vegetables, and increased carbohydrate intake. RAC1 polymorphisms were associated with biochemical parameters in diabetics: rs7784465 (P=0.015) and rs836478 (P=0.028) with increased glycated hemoglobin, rs836478 (P=0.005) with increased fasting blood glucose, oxidized glutathione (P=0.012), and uric acid (P=0.034). Haplotype rs4724800A-rs7784465C-rs10951982G-rs10238136A-rs836478C-rs9374G was strongly associated with increased levels of hydrogen peroxide (P<0.0001). Thus, polymorphisms in the RAC1 gene represent novel genetic markers of type 2 diabetes, and their link with glucose metabolism and disease pathogenesis is associated with the changes in redox homeostasis.

PMID:35416295 | DOI:10.1111/eci.13792

Turk Neurosurg. 2021 Oct 22. doi: 10.5137/1019-5149.JTN.35974-21.2. Online ahead of print.

ABSTRACT

AIM: Our objective was to determine the rate of postoperative complications following surgery for Scheuermann’s kyphosis (SK) and ascertain whether restoration to an ideal Roussouly spine type reduced the incidence of postoperative proximal junctional kyphosis (PJK).

MATERIAL AND METHODS: We retrospectively screened all patients undergoing SK surgery at our institution (2010-2017) and excluded patients with less than two years of follow-up. Postoperative complications were identified as early or late and minor or major. Successful restoration of Roussouly spine type was assessed and patients were classified as “restored” or “non-restored.” Associations between ideal Roussouly restoration and postoperative PJK were evaluated using logistic regression analysis.

RESULTS: The study included 22 patients with a median age of 23 (IQR, 20.0-43.8) years. Postoperative complications developed in 17 (77%) of these cases. All 17 patients developed minor complications; seven (32%) patients also exhibited major complications. PJK was diagnosed in 55% of the patients with an 18% overall two-year revision rate. Forty-four percent of the patients in the restored group developed PJK compared to 83% in the non-restored group (p=0.162). Multivariable logistic regression analysis revealed a trend towards an increased incidence of PJK in the non-restored group, albeit without statistical significance (OR, 9.4; 95% CI, 0.7-122.5, p=0.087).

CONCLUSION: Our study revealed that 77% of patients undergoing surgery for SK developed at least one complication with a two-year revision rate of 18%. PJK was detected less frequently in patients who were restored to their ideal Roussouly spine type, although this finding did not achieve statistical significance.

PMID:35416264 | DOI:10.5137/1019-5149.JTN.35974-21.2

J Sports Med Phys Fitness. 2022 Apr 12. doi: 10.23736/S0022-4707.22.13107-5. Online ahead of print.

ABSTRACT

BACKGROUND: Exercise associated collapse (EAC) is a common medical encounter at distance running events. Risk factors associated with EAC are not well documented. The objective is to determine the overall incidence of EAC and identify risk factors associated with EAC in 21.1km and 56km runners.

METHODS: A cross-sectional analysis of 153208 race starters from the Two Oceans Marathon races (2008-2015). All EACs on race day were documented by medical staff. Risk factors associated with EAC investigated included demographics, race distance (21.1km vs. 56km), running speed, race experience and race day environmental data (wet-bulb globe temperature [WBGT], humidity, wind speed). Incidence (per 1000 starters; 95%CIs) and incidence ratios (95%CIs) were calculated.

RESULTS: The overall incidence of EAC was 1.50 (95% CI 1.31-1.71). Longer race distance (IR: 2.1; 1.6-2.7; p<0.0001) and slower running speed (IR: 1.3; 1.1-1.5; p=0.0017) were significant risk factors associated with EAC. The incidence of EAC was higher in female vs. male 21.1km race starters (IR=2.25; 1.47-3.46; p=0.0229). Age and environmental conditions were not associated with EAC (p>0.05) in a cool and temperate environment.

CONCLUSIONS: About 1 in 667 race starters (21.1km and 56km) develop EAC. Longer race distance, slower running speed and female sex (in 21.1km starters) are significant risk factors associated with EAC. Race medical directors can identify race entrants that may be at risk of developing EAC, develop prevention strategies and better prepare medical care at these events.

PMID:35415992 | DOI:10.23736/S0022-4707.22.13107-5

Health Expect. 2022 Apr 12. doi: 10.1111/hex.13495. Online ahead of print.

ABSTRACT

BACKGROUND: Stigma is a formidable burden for survivors of lung cancer that can reduce the quality of life (QOL), resulting in physical, social and psychological challenges. This study investigates associations between stigma and depression, QOL and demographic and health-related characteristics, including race.

DESIGN: An adapted conceptual model derived from the Cataldo Lung Cancer Stigma Scale guided this descriptive correlation study assessing stigma in African American and Caucasian survivors of lung cancer. Self-reported, written surveys measuring depression, QOL, lung cancer stigma and demographics were administered. Statistical analysis was conducted to assess associations between stigma and depression, stigma and QOL and stigma and race, while adjusting for demographic characteristics.

RESULTS: Participants (N = 56) included 30 Caucasian and 26 African American survivors of lung cancer recruited from a cancer registry of an American College of Surgeons-accredited programme, a survivors’ support club and an ambulatory oncology practice in the southeastern United States. Statistical analysis yielded (1) a significant moderate positive association between depression and lung cancer stigma; (2) a significant moderate negative association between QOL and lung cancer stigma; and (3) significant relationships between race and lung cancer stigma, specifically higher degree of stigma among African Americans compared to Caucasians.

CONCLUSION: Stigma affects many aspects of survivors’ lives. Healthcare professionals need to consider how health-related stigma may further complicate the physical burdens, psychological distresses and social challenges that accompany the disease, especially among African American survivors. Additional enquiry and interventions are needed to assist with mitigating the negative effects of stigma on survivors and their family members and friends.

PATIENT OR PUBLIC CONTRIBUTION: Fifty-six survivors of lung cancer participated in this descriptivecorrelation study. They completed written surveys measuring depression, QOL, and lung cancer stigma, plus an investigator-developed demographic information form.

PMID:35415934 | DOI:10.1111/hex.13495

Isr Med Assoc J. 2022 Apr;24(4):241-245.

ABSTRACT

BACKGROUND: It is important to predict acute cholecystitis (AC) before a laparoscopic cholecystectomy because inflammation of the gallbladder predicts the need for open conversion and subsequent morbidity after a laparoscopic cholecystectomy.

OBJECTIVES: To create an index based on clinical, laboratory, and ultrasound criteria on admission that will predict AC on pathological examination in patients presenting acutely.

METHODS: We retrospectively reviewed consecutive cases of emergency laparoscopic cholecystectomies conducted by three experienced surgeons between 1 October 2014 and 31 January 2018. Independent variables were age, sex, presenting symptoms, admission laboratory tests, and ultrasound findings. The outcome variable was AC on histological examination. An index was created from all variables that added significantly to the logistic regression analysis.

RESULTS: Eight variables that contributed significantly to the model, included age, male sex, vomiting on admission, an increased proportion of neutrophils, a normal aspartate aminotransferase test, a normal serum amylase test result, a thick gall bladder wall, and pericholecystic fluid. An index of ≤ 2 to ≥ 8 created from those variables had a graded risk for AC of 1.8% to 92.0% with a c-statistic of 0.86 (95% confidence interval 0.81-0.91). Operating time and bleeding increased in those with a higher index.

CONCLUSIONS: An index including age, sex, symptoms, and selected laboratory results as well as ultrasound characteristics had an excellent graded risk in the prediction of histological AC that was associated with operating time and an increased risk of bleeding during the operation.

PMID:35415983

Br J Haematol. 2022 Apr 12. doi: 10.1111/bjh.18205. Online ahead of print.

NO ABSTRACT

PMID:35415917 | DOI:10.1111/bjh.18205

Eur J Cancer Care (Engl). 2022 Apr 12:e13591. doi: 10.1111/ecc.13591. Online ahead of print.

ABSTRACT

OBJECTIVE: Systematic depression screening is recommended for older patients with cancer. The objective of this study was to evaluate the performance of three mood disorder screening scales frequently used in geriatric oncology to help in diagnosing major depressive disorder (MDD).

METHODS: A prospective multicentre study was conducted in patients 70 years of age and over with cancer, comparing three self-report questionnaires: the 15-item Geriatric Depression Scale (GDS-15), the Hospital Anxiety and Depression Scale – Depression (HADS-D) and the Distress Thermometer (DT). In the event of abnormal scores, a psychologist consultation was suggested and a reassessment of the patient’s mood was planned within 3 weeks. Potential differences between initial abnormal screening score and confirmed MDD (according to the Diagnostic and Statistical Manual of Mental Disorders criteria [DSM-5]) were assessed using variance analysis for each screening scale.

RESULTS: Ninety-three patients with a median age of 81 years (70-95) were included. Sixty-six patients had at least one abnormal score on one of the screening scales. MDD was confirmed in 10 of the 36 reassessed patients. Analysis of ROC curves showed that the HADS-D significantly predicted MDD (AUC = 0.760, IC_95% : 0.603-0.917; p = 0.017), but not the GDS-15 or the initial DT.

CONCLUSION: The HADS-D could better detect MDD, to confirm in a larger sample.

PMID:35415901 | DOI:10.1111/ecc.13591

Ann Surg Oncol. 2022 Apr 12. doi: 10.1245/s10434-022-11521-4. Online ahead of print.

ABSTRACT

BACKGROUND: The BREAST-Q is the most commonly used patient-reported outcome measure (PROM) for breast reconstruction research. However, clinical implementation of this PROM has been impeded by a lack of context for score interpretation. The aim of this study was to define reference values for the BREAST-Q at discrete timepoints following surgery, generating a tool for real-time score interpretation.

METHODS: BREAST-Q scores were prospectively obtained in women who underwent implant or autologous post-mastectomy breast reconstruction preoperatively and for 2 years following surgery at Memorial Sloan Kettering Cancer Center (MSK). Descriptive statistics were used to create reference values for BREAST-Q satisfaction and quality-of-life subscales. Reference values were externally validated by comparing patient characteristics and BREAST-Q scores between the MSK and the Mastectomy Reconstruction Outcomes Consortium (MROC) study cohorts.

RESULTS: Overall, 3268 MSK patients and 2814 MROC patients were included for analysis. When MSK and MROC cohorts were compared for validation, there were some statistical differences in BREAST-Q scores; however, most of these differences did not meet the minimal clinically important difference of 4 points. Reference values were used to create the BREAST-Q Real-time Engagement and Communication Tool (REACT).

CONCLUSIONS: Using a large cohort of patients, we have defined BREAST-Q reference values for post-mastectomy breast reconstruction patients for use in clinical practice. The BREAST-Q REACT will help breast reconstruction providers gauge patient wellbeing and satisfaction relative to the “average” breast reconstruction patient and determine which patients may benefit from additional intervention.

PMID:35415816 | DOI:10.1245/s10434-022-11521-4

Andrologia. 2022 Apr 12:e14432. doi: 10.1111/and.14432. Online ahead of print.

ABSTRACT

Numerous studies conducted to study the role of testosterone in erectile dysfunction (ED) extensively, but less is known of the association between estradiol level and ED. To assess the strong association between estradiol and ED by quantitatively synthesizing all studies evaluating the relationship between estradiol and ED. An extensive literature search was conducted by two authors independently in three electronic databases, including PubMed, Web of Science and Cochrane Library, up to January 10, 2021. The Patient Population or Problem, Intervention, Comparison, Outcomes and Setting (PICOS) were used for inclusion criteria to identify studies. The Newcastle-Ottawa Scale was applied to assess the quality of studies. The standardized mean difference (SMD) and their corresponding 95% confidence intervals (95% CIs) were used to compare the estradiol level between ED patients and healthy subjects, and the pooled OR and 95%CI were used to evaluate the strong association between estradiol level and ED. Finally, six studies were included in this meta-analysis, satisfying predefined inclusion criteria. Five studies were considered to be high quality, and only one was judged of moderate quality. The estradiol level of ED patients was statistically higher than that in healthy subjects (SMD 0.45, 95%CI 0.28-0.63, p <0.0001). The pooled OR demonstrated that the estradiol was correlated to the ED significantly (OR 1.08, 95%CI 1.05-1.12, p <0.0001). Subgroup analyses were conducted based on age, diagnosis way, country, sample size, detection method and estradiol level. There was no substantial change in the result of SMD ranging from 0.41 (95% CI 0.31-0.51) to 0.53 (95% CI 0.44-0.62) when performing sensitivity analysis. No publication bias was detected by the Begg test or Egger test. This meta-analysis demonstrated that the estradiol level is correlated to ED significantly.

PMID:35415900 | DOI:10.1111/and.14432

J Med Toxicol. 2022 Apr 12. doi: 10.1007/s13181-022-00890-7. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the evidence in support of the use of buprenorphine in the treatment of OUD and increasing ability of emergency medicine (EM) clinicians to prescribe it, emergency department (ED)-initiated buprenorphine is uncommon. Many EM clinicians lack training on how to manage acute opioid withdrawal or initiate treatment with buprenorphine. We developed a brief buprenorphine training program and assessed the impact of the training on subsequent buprenorphine initiation and knowledge retention.

METHODS: We conducted a pilot randomized control trial enrolling EM clinicians to receive either a 30-min didactic intervention about buprenorphine (standard arm) or the didactic plus weekly messaging and a monetary inducement to administer and report buprenorphine use (enhanced arm). All participants were incentivized to complete baseline, immediate post-didactic, and 90-day knowledge and attitude assessment surveys. Our objective was to achieve first time ED buprenorphine prescribing events in clinicians who had not previously prescribed buprenorphine in the ED and to improve EM-clinician knowledge and perceptions about ED-initiated buprenorphine. We also assessed whether the incentives and reminder messaging in the enhanced arm led to more clinicians administering buprenorphine than those in the standard arm following the training; we measured changes in knowledge of and attitudes toward ED-initiated buprenorphine.

RESULTS: Of 104 EM clinicians enrolled, 51 were randomized to the standard arm and 53 to the enhanced arm. Clinical knowledge about buprenorphine improved for all clinicians immediately after the didactic intervention (difference 19.4%, 95% CI 14.4% to 24.5%). In the 90 days following the intervention, one-third (33%) of all participants reported administering buprenorphine for the first time. Clinicians administered buprenorphine more frequently in the enhanced arm compared to the standard arm (40% vs. 26.3%, p = 0.319), but the difference was not statistically significant. The post-session knowledge improvement was not sustained at 90 days in the enhanced (difference 9.6%, 95% CI – 0.37% to 19.5%) or in the standard arm (difference 3.7%, 95% CI – 5.8% to 13.2%). All the participants reported an increased ability to recognize patients with opioid withdrawal at 90 days (enhanced arm difference .55, 95% CI .01-1.09, standard arm difference .85 95% CI .34-1.37).

CONCLUSIONS: A brief educational intervention targeting EM clinicians can be utilized to achieve first-time prescribing and improve knowledge around buprenorphine and opioid withdrawal. The use of weekly messaging and gain-framed incentivization conferred no additional benefit to the educational intervention alone. In order to further expand evidence-based ED treatment of OUD, focused initiatives that improve clinician competence with buprenorphine should be explored.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03821103.

PMID:35415804 | DOI:10.1007/s13181-022-00890-7