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Nevin Manimala Statistics

Does pregabalin act in pain control after lateral pharyngoplasties and tonsillectomies? A pilot study

Sleep Breath. 2022 Sep 29. doi: 10.1007/s11325-022-02715-x. Online ahead of print.

ABSTRACT

OBJECTIVE: Some studies have pointed to gabapentinoids as promising medications in postoperative pain control. The objective of the present study was to evaluate the efficacy of pregabalin in reducing postoperative pain in tonsillectomy and lateral pharyngoplasties.

STUDY DESIGN: Double-blind randomized controlled trial.

SETTING: Tertiary care center.

METHODS: A double-blind randomized controlled trial was conducted with patients undergoing tonsillectomies and lateral pharyngoplasties between Aug 29, 2017, and Oct 31, 2020. Data of interest such as opioid consumption, pain scores, and adverse outcomes such as dizziness, nausea, headache, and sedation within 7 days following surgeries were analyzed.

RESULTS: No statistically significant difference was observed in pain scores and opioid consumption between the groups studied in the pilot project. The use of pregabalin was associated with lower incidence of dizziness compared to controls.

CONCLUSION: Gabapentinoids, especially pregabalin, are drugs whose potential for controlling pain after pharyngeal surgery, such as tonsillectomy and sleep apnea surgery, still needs to be more fully evaluated. After the conclusion of the present study, we hope to answer this question about the role of pregabalin in oropharyngeal surgeries.

PMID:36171512 | DOI:10.1007/s11325-022-02715-x

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Nevin Manimala Statistics

Learning curve for the surgical time of laparoscopic cholecystectomy performed by surgical trainees using the three-port method: how many cases are needed for stabilization?

Surg Endosc. 2022 Sep 28. doi: 10.1007/s00464-022-09666-0. Online ahead of print.

ABSTRACT

BACKGROUND: The assessment of laparoscopic cholecystectomy (LC) skills using operating times has not been well reported. We examined the total and partial operating times for LC procedures performed by surgical trainees to determine the required number of surgeries until the surgical time stabilizes.

METHODS: We reviewed the video records of 514 consecutive LCs using the three-port method, performed by 16 surgical trainees. The total and partial surgical times were calculated and correlated to the surgeons’ experience.

RESULTS: The median total surgical time for a trainee’s first LC was 112 (range 71-226) minutes. It reduced rapidly after the first 20 LCs and plateaued to its minimum after approximately 60 cases. A statistically significant time decrease was observed between the first 10 (median, range 112, 46-252 min) and the next 50-59 cases (64, 34-198 min), but not between the 50-59 and the subsequent 100-109 cases (71, 33-127 min). The total times taken by trainees who had performed > 50 operations were not significantly different from those taken by instructors during the study period. Surgery for 125 patients with acute cholecystitis took a significantly longer time (median 99 vs. 74 min with non-acute cholecystitis); however, the abovementioned time reduction findings showed similar results regardless of the patient’s acute inflammation status. The partial operating times around the cervical/cystic duct and gallbladder bed reduced uniformly between the first 10 and the following 50-59 cases. Although time variations in total and cervical/cystic duct operating times were not correlated to the surgical experience, time fluctuation of gallbladder bed procedures reduced after 60 cases.

CONCLUSION: The time required to perform an LC was inversely correlated with the experience of surgical trainees and halved after the first 60 cases. The surgical experience required for LC time stabilization is approximately 60 cases.

PMID:36171452 | DOI:10.1007/s00464-022-09666-0

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Nevin Manimala Statistics

Assessment of small in-frame indels and C-terminal nonsense variants of BRCA1 using a validated functional assay

Sci Rep. 2022 Sep 28;12(1):16203. doi: 10.1038/s41598-022-20500-4.

ABSTRACT

BRCA1 (Breast Cancer 1, early onset) is linked to breast and ovarian cancer predisposition. Still, the risks conferred by a significant portion of BRCA1 variants identified in the population remains unknown. Most of these variants of uncertain significance are missense alterations. However, the functional implications of small in-frame deletions and/or insertions (indels) are also difficult to predict. Our group has previously evaluated the functional impact of 347 missense variants using an extensively validated transcriptional activity assay. Here we show a systematic assessment of 30 naturally occurring in-frame indels located at the C-terminal region of BRCA1. We identified positions sensitive and tolerant to alterations, expanding the knowledge of structural determinants of BRCA1 function. We further designed and assessed the impact of four single codon deletions in the tBRCT linker region and six nonsense variants at the C-terminus end of BRCA1. Amino acid substitutions, deletions or insertions in the disordered region do not significantly impact activity and are not likely to constitute pathogenic alleles. On the other hand, a sizeable fraction of in-frame indels at the BRCT domain significantly impact function. We then use a Bayesian integrative statistical model to derive the probability of pathogenicity for each variant. Our data highlights the importance of assessing the impact of small in-frame indels in BRCA1 to improve risk assessment and clinical decisions for carriers.

PMID:36171434 | DOI:10.1038/s41598-022-20500-4

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Nevin Manimala Statistics

Drug genetic associations with COVID-19 manifestations: a data mining and network biology approach

Pharmacogenomics J. 2022 Sep 28. doi: 10.1038/s41397-022-00289-1. Online ahead of print.

ABSTRACT

Available drugs have been used as an urgent attempt through clinical trials to minimize severe cases of hospitalizations with Coronavirus disease (COVID-19), however, there are limited data on common pharmacogenomics affecting concomitant medications response in patients with comorbidities. To identify the genomic determinants that influence COVID-19 susceptibility, we use a computational, statistical, and network biology approach to analyze relationships of ineffective concomitant medication with an adverse effect on patients. We statistically construct a pharmacogenetic/biomarker network with significant drug-gene interactions originating from gene-disease associations. Investigation of the predicted pharmacogenes encompassing the gene-disease-gene pharmacogenomics (PGx) network suggests that these genes could play a significant role in COVID-19 clinical manifestation due to their association with autoimmune, metabolic, neurological, cardiovascular, and degenerative disorders, some of which have been reported to be crucial comorbidities in a COVID-19 patient.

PMID:36171417 | DOI:10.1038/s41397-022-00289-1

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Molecular imaging of fibroblast activity in pressure overload heart failure using [68 Ga]Ga-FAPI-04 PET/CT

Eur J Nucl Med Mol Imaging. 2022 Sep 29. doi: 10.1007/s00259-022-05984-6. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to evaluate whether [68 Ga]Ga-FAPI-04 PET/CT could characterize the early stages of cardiac fibrosis in pressure overload heart failure.

METHODS: Sprague-Dawley rats underwent abdominal aortic constriction (AAC) (n = 12) and sham surgery (n = 10). All rats were scanned with [68 Ga]Ga-FAPI-04 PET/CT at 2, 4, and 8 weeks after surgery. The expression of fibroblast activation protein (FAP) in the myocardium was detected by immunohistochemistry. [68 Ga]Ga-FAPI-04 PET signal and FAP expression were compared between two groups.

RESULTS: Compared with the sham group, the AAC group presented with decreased ejection fraction (EF) and fractional shortening (FS) and increased left ventricular internal dimensions in diastole (LVIDd) and systole (LVIDs) at 4 and 8 weeks (all p < 0.01). The AAC group showed higher [68 Ga]Ga-FAPI-04 accumulation in the heart than the sham group at 2, 4, and 8 weeks, and FAPI increased significantly from 2 to 8 weeks (all p < 0.001). Immunohistochemistry confirmed the higher density of the FAP+ area in the AAC group. The intensity of the [68 Ga]Ga-FAPI-04 correlated with the density of the FAP+ area (p < 0.001). The expression of the [68 Ga]Ga-FAPI-04 at 4 weeks correlated with the deterioration of cardiac function at 8 weeks (EF: R = – 0.87; FS: R = – 0.72; LVIDd: R = 0.77; LVIDs: R = 0.79; all p < 0.001). The AAC group also showed an increased [68 Ga]Ga-FAPI-04 signal in the liver, peaking at 4 weeks and then declining. Cardiac and liver PET signals correlated at 4 weeks in the AAC group (R = 0.69, p = 0.0010), suggesting an early fibrotic link between organs. A combination of the [68 Ga]Ga-FAPI-04 intensity in the heart and liver at 4 weeks better predicted the deterioration of cardiac function at 8 weeks.

CONCLUSIONS: The activated fibroblasts in the heart and liver after pressure overload can be monitored by [68 Ga]Ga-FAPI-04 PET/CT, which reveals an early fibrotic link in cardio-liver interactions and could better predict nonischemic heart failure prognosis.

PMID:36171409 | DOI:10.1007/s00259-022-05984-6

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Association between carbon monoxide poisoning and adrenal insufficiency: a nationwide cohort study

Sci Rep. 2022 Sep 28;12(1):16219. doi: 10.1038/s41598-022-20584-y.

ABSTRACT

Carbon monoxide poisoning may damage the brain and adrenal glands, but it is unclear whether it is associated with adrenal insufficiency. We identified all COP patients diagnosed between 1999 and 2012 in Taiwan using the Nationwide Poisoning Database and selected a reference cohort (participants without COP) from the same database by exact matching of age and index date at a 1:2 ratio. Participants with a history of adrenal insufficiency or steroid use of more than 14 days were excluded. We followed up participants until 2013 and compared the risk of developing adrenal insufficiency between the two cohorts. The 21,842 COP patients had a higher risk for adrenal insufficiency than the 43,684 reference participants (adjusted hazard ratio [AHR] = 2.5; 95% confidence interval [CI]: 1.8-3.5) after adjustment for sex and underlying comorbidities (liver disease, thyroid disease, mental disorder). The risk continued to elevate even after 1 year (AHR = 2.1; 95% CI: 1.4-3.4). The COP patients who had acute respiratory failure had an even higher risk for adrenal insufficiency than those without acute respiratory failure, which may indicate a dose-response relationship. Stratified analyses showed that female patients had an elevated risk (AHR = 3.5; 95% CI: 2.1-6.0), but not male patients. Younger patients (< 50 years) had higher risks, and the AHR reached statistical significance in the age groups 20-34 (AHR = 5.5; 95% CI: 1.5-20.6) and 35-49 (AHR = 4.9; 95% CI: 2.3-10.6) years old. The risk for developing adrenal insufficiency elevated after COP, especially in female and younger patients. Carbon monoxide is the most common gaseous agent causing acute intoxication worldwide. Results of the current study call for monitoring adrenal function of patients with COP.

PMID:36171402 | DOI:10.1038/s41598-022-20584-y

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Nevin Manimala Statistics

Association of underweight status with the risk of tuberculosis: a nationwide population-based cohort study

Sci Rep. 2022 Sep 28;12(1):16207. doi: 10.1038/s41598-022-20550-8.

ABSTRACT

In studies evaluating the association between body mass index (BMI) and risk of tuberculosis (TB), the data for the underweight population has been limited and results were conflicting. Our study aimed to evaluate whether being underweight increases the risk of TB using a nationwide representative sample from the Republic of Korea. A large population-based cohort study of over ten million subjects who participated in the health screening in 2010 was performed using the Korean National Health Insurance database 2010-2017. We evaluated the incidence and risk of TB by BMI category (kg/m2) for Asians using a multivariable Cox regression model, adjusting for age, sex, smoking, alcohol consumption, regular exercise, low-income state, and underlying hypertension, diabetes mellitus, and dyslipidemia. To evaluate the association between BMI and TB risk, the underweight population was further subdivided according to the degree of thinness. During 70,063,154.3 person-years of follow-up, 52,615 of 11,135,332 individuals developed active TB with an incidence of 0.75 per 1000 person-years. Overall, there was a log-linear inverse relationship between TB incidence and BMI, within the BMI range of 15-30 kg/m2 (R2 = 0.95). The estimated adjusted hazard ratio (HR) for incident TB in the underweight population (BMI < 18.5) was 2.08 (95% confidence intervals, CI 2.02-2.15), overweight (23 ≤ BMI < 25) was 0.56 (0.55-0.58) and obese (BMI ≥ 25) was 0.40 (0.39-0.41) relative to the normal weight population. Among the underweight population, TB risk increased as the degree of thinness increased (adjusted HR = 1.98, 1.91-2.05; 2.50, 2.33-2.68; and 2.83, 2.55-3.15, for mild, moderate and severe thinness, respectively) (p for trend < 0.001). We found a significant inverse relationship between BMI and TB incidence, which was especially profound in the underweight population. Public health strategies to screen TB more actively in the underweight population and improve their weight status may help reduce the burden of TB.

PMID:36171396 | DOI:10.1038/s41598-022-20550-8

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Nevin Manimala Statistics

Time to castration resistance is a novel prognostic factor of cancer-specific survival in patients with nonmetastatic castration-resistant prostate cancer

Sci Rep. 2022 Sep 28;12(1):16202. doi: 10.1038/s41598-022-20319-z.

ABSTRACT

We aimed to identify prognostic factors of cancer-specific survival (CSS) in non-metastatic castration-resistant prostate cancer (M0CRPC) patients. The final analysis of this retrospective cohort included 82 patients who were diagnosed as M0CRPC between 1998 and 2018 at the University of Tokyo Hospital. CRPC was defined as prostate-specific antigen (PSA) progression (increased PSA ≥ 25% and ≥ 2 ng/mL above the nadir or detection of a metastatic lesion). The median value of age and PSA at the time of CRPC were 76 (range 55-94) years and 2.84 (range 2.04-22.5) ng/mL, respectively. The median follow-up time from CRPC diagnosis was 38 (range 3-188) months. The prognostic factors of CSS were ‘PSA doubling time (PSADT) ≤ 3 months’, ‘time to CRPC diagnosis from the start of androgen deprivation therapy (TTCRPC) ≤ 12 months’, of which TTCRPC was a novel risk factor of CSS. In the multivariate analysis, ‘PSADT ≤ 3 months’ and TTCRPC ≤ 12 months’ remained as statistically significant predictors of CSS. Novel risk stratification was developed based on the number of these risk factors. The high-risk group showed a hazard ratio of 4.416 (95% confidence interval 1.701-11.47, C-index = 0.727).

PMID:36171391 | DOI:10.1038/s41598-022-20319-z

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Nevin Manimala Statistics

Implementing Bundle Care in Major Abdominal Emergency Surgery: Long-Term Mortality and Comprehensive Complication Index

World J Surg. 2022 Sep 28. doi: 10.1007/s00268-022-06763-y. Online ahead of print.

ABSTRACT

BACKGROUND: Major abdominal emergency surgery (MAES) has a high risk of postoperative mortality and a high complication rate. The aim of this study was to evaluate whether the implementation of a perioperative care bundle reduced long-term mortality and the Comprehensive Complication Index (CCI) after MAES.

METHODS: This study was a single-centre retrospective cohort study. Data in the intervention group were collected prospectively and compared with a historical cohort from the same centre. It includes adult patients undergoing MAES. We implemented a care bundle under the name Abdominal Surgery Acute Protocol (ASAP). We initiated fast-track initiatives and standardised optimised care in before, during and after surgery. Data were analysed using survival analysis and multiple regression.

RESULTS: We included 120 patients in the intervention cohort and 258 in the historical cohort. The one-year mortality rate was 21.7% in the intervention cohort compared to 28.3% in the standard care cohort. Adjusted odds ratio of one-year mortality 0.81 (CI95% 0.41-1.56). The 30-day mortality was lowered from 19.0 to 6.7% (p = 0.003). The CCI in the intervention cohort was 8.7 (IQR 0-34) compared to 21 (IQR 0-36) in the control cohort (p = 0.932) The length of stay increased by two days (p = 0.021). Most cases had 71-80% protocol compliance.

CONCLUSION: Implementing bundle care in major abdominal emergency surgery lowered the 30-day postoperative mortality. The difference in mortality was preserved over time although not significant after one year. The changes in the Comprehensive Complication Index were not statistically significant.

PMID:36171351 | DOI:10.1007/s00268-022-06763-y

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Cryptogenic Stroke In The Context of Pandemic-Related Stress: The Role of Arterial Hemodynamics

Psychiatr Danub. 2022 Sep;34(Suppl 8):256-261.

ABSTRACT

BACKGROUND: Up to 45% of ischemic strokes are cryptogenic, which is an impediment to proposing preventative measures. In this investigation we aimed to study underlying heart arrhythmias in patients with cryptogenic stroke, taking into consideration the context of the COVID-19 pandemic and stressful lockdown conditions.

SUBJECTS AND METHODS: In this cross-sectional study we observed 52 patients with cryptogenic stroke >1 month after acute presentation, and a control group consisting of 88 patients without stroke. All patients undewent the laboratory and instrumental investigation consisting of the following: lipid spectrum; hemostasiograms; hemoglobin A1c; transthoracic or/and transesophageal echocardiography; 24-hours monitoring of ECG; computer tomography or magnetic resonance imaging of the brain. We studied the hemodynamics of the common carotid arteries using Doppler ultrasound imaging and digital sphygmography (SG).

RESULTS: The groups were indentical with respect to the preponderance of study parameters (sex, age, comorbidities, instrumental and laboratory data). The ischemic stroke group had a statistically significant difference in the prevalence of the first type of extrasystolic arrhythmia according to our gradation of extrasystoles, which are ventricular systoles of extrasystolic contraction appearing before the transmitral blood flow peak (peak E in echocardiography). We observed that earlier ventricular systoles of extrasystole in the cardiac cycle predicted for greater growth of hemodynamic and kinetic parameters. Calculating the indices of a four-field table established the significant relationship between the moment of appearance of extrasystolic ventricular contraction in the cardiac cycle and the risk for cryptogenic stroke (normalized value of the Pearson coefficient (C`) of the two paramaters was 0.318).

CONCLUSIONS: Extrasystolic arrhythmia appeared as an additional risk factor of earlier stroke. The most dangerous type of arrhythmia was when the ventricular contraction of the extrasystole appeared before the transmitral blood flow peak in the cardiac cycle. This observation could present a risk-marker for brain-related cardiovascular complications such as stroke, which might be patients suffering from different internal diseases, especially in the context of environmental stress conditions of the current pandemic and its related lockdown measures.

PMID:36170739