Nevin Manimala

Postgrad Med J. 2021 Oct 5:postgradmedj-2021-140674. doi: 10.1136/postgradmedj-2021-140674. Online ahead of print.

ABSTRACT

PURPOSE OF THE STUDY: Hypertension is one of the most common comorbidities in COVID-19 pneumonia. However, whether it is an independent factor on the severity and mortality of COVID-19 has not been studied.

STUDY DESIGN: In this study, 736 patients with a PCR-confirmed diagnosis of COVID-19 were included from 12 January 2020 to 25 March 2020. All patients were divided into two groups according to whether or not they were hypertensive. After propensity score matching (PSM) to remove the interference of mismatches in the baseline data, the clinical characteristics and outcomes of angiotensin II receptor blocker (ARB)/ACE inhibitors application were analysed.

RESULTS: A total of 220 (29.9%) patients were hypertensive, and 516 (70.1%) patients were not hypertensive. PSM eliminated demographic and comorbidity differences between the two groups. Of all participants, 32 patients died (4.3% mortality), including 17 out of 220 in the hypertension group (7.7%) and 15 out of 516 in the non-hypertension group (2.9%). The incidence of intensive care unit (ICU) stay in the hypertension group (12.8%) was higher than in the non-hypertension group (5.3%) (p<0.05). Logistic regression analysis showed that hypertension was an independent risk factor for death, not other comorbidities. Kaplan-Meier analysis showed that mortality was higher in the hypertension group than in the non-hypertension group before and after PSM (p<0.05). There was no statistically significant difference in ICU therapy, mortality and hospitalisation time between hypertensive patients with or without ARBs/ACE inhibitors (p>0.05).

CONCLUSION: Hypertension was an independent risk factor for the severity and mortality of patients with COVID-19. ARBs/ACE inhibitors should not be discontinued in hypertensive patients with COVID-19.

PMID:34611036 | DOI:10.1136/postgradmedj-2021-140674

Postgrad Med J. 2021 Oct 5:postgradmedj-2021-140886. doi: 10.1136/postgradmedj-2021-140886. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: White matter lesions (WMLs) are thought to cause damage to the blood-brain barrier, thereby aggravating bleeding after intravenous thrombolysis. However, the risk factors for symptomatic cerebral haemorrhage after thrombolysis are still unclear. This study explored the risk factors for bleeding in patients with severe WMLs after intravenous thrombolysis to prevent bleeding as soon as possible.

METHODS: A large single-centre observational study conducted a retrospective analysis of intravenous thrombolysis in patients with severe WMLs from January 2018 to March 2021. According to whether symptomatic cerebral haemorrhage occurred, the patients were divided into two groups, and then statistical analysis was performed.

RESULTS: After a retrospective analysis of the data of nearly 1000 patients with intravenous thrombolysis and excluding invalid information, 146 patients were included, of which 23 (15.8%) patients had symptomatic cerebral haemorrhage. Univariate analysis showed that a history of hypertension (20% vs 4.9%, p=0.024), hyperlipidaemia (38.7% vs 9.6%, p<0.001), the National Institutes of Health Stroke Scale (NIHSS) score before thrombolysis (median 17 vs 6, p<0.001), low-density lipoprotein levels (median 2.98 vs 2.44, p=0.011), cholesterol levels (mean 4.74 vs 4.22, p=0.033), platelet count (median 161 vs 191, p=0.031), platelet distribution width (median 15.2 vs 12.1, p=0.001) and sodium ion levels (median 139.81 vs 138.67, p=0.043) were significantly associated with symptomatic cerebral haemorrhage. Further multivariate logistic regression analysis showed that hyperlipidaemia (OR=9.069; 95% CI 2.57 to 32.07; p=0.001) and the NIHSS score before thrombolysis (OR=1.33; 95% CI 1.16 to 1.52; p<0.001) were comprehensive risk factors for symptomatic cerebral haemorrhage.

CONCLUSION: Hyperlipidaemia and the NIHSS score before thrombolysis are independent risk factors for bleeding after intravenous thrombolysis in patients with severe WMLs. Delaying the onset of white matter and preventing risk factors for bleeding will help improve the prognosis of cerebral infarction and reduce mortality. These risk factors need to be further evaluated in future studies.

PMID:34611035 | DOI:10.1136/postgradmedj-2021-140886

Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):e2113028118. doi: 10.1073/pnas.2113028118.

ABSTRACT

The aim of this study was to develop an interventional optical imaging (OI) technique for intraprocedural guidance of complete tumor ablation. Our study employed four strategies: 1) optimizing experimental protocol of various indocyanine green (ICG) concentrations/detection time windows for ICG-based OI of tumor cells (ICG cells); 2) using the optimized OI to evaluate ablation-heat effect on ICG cells; 3) building the interventional OI system and investigating its sensitivity for differentiating residual viable tumors from nonviable tumors; and 4) preclinically validating its technical feasibility for intraprocedural monitoring of radiofrequency ablations (RFAs) using animal models with orthotopic hepatic tumors. OI signal-to-background ratios (SBRs) among preablation tumors, residual, and ablated tumors were statistically compared and confirmed by subsequent pathology. The optimal dose and detection time window for ICG-based OI were 100 μg/mL at 24 h. Interventional OI displayed significantly higher fluorescence signals of viable ICG cells compared with nonviable ICG cells (189.3 ± 7.6 versus 63.7 ± 5.7 au, P < 0.001). The interventional OI could differentiate three definitive zones of tumor, tumor margin, and normal surrounding liver, demonstrating significantly higher average SBR of residual viable tumors compared to ablated nonviable tumors (2.54 ± 0.31 versus 0.57 ± 0.05, P < 0.001). The innovative interventional OI technique permitted operators to instantly detect residual tumors and thereby guide repeated RFAs, ensuring complete tumor eradication, which was confirmed by ex vivo OI and pathology. In conclusion, we present an interventional oncologic technique, which should revolutionize the current ablation technology, leading to a significant advancement in complete treatment of larger or irregular malignancies.

PMID:34611022 | DOI:10.1073/pnas.2113028118

Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):e2110239118. doi: 10.1073/pnas.2110239118.

ABSTRACT

Eukaryotic cells are mechanically supported by a polymer network called the cytoskeleton, which consumes chemical energy to dynamically remodel its structure. Recent experiments in vivo have revealed that this remodeling occasionally happens through anomalously large displacements, reminiscent of earthquakes or avalanches. These cytoskeletal avalanches might indicate that the cytoskeleton’s structural response to a changing cellular environment is highly sensitive, and they are therefore of significant biological interest. However, the physics underlying “cytoquakes” is poorly understood. Here, we use agent-based simulations of cytoskeletal self-organization to study fluctuations in the network’s mechanical energy. We robustly observe non-Gaussian statistics and asymmetrically large rates of energy release compared to accumulation in a minimal cytoskeletal model. The large events of energy release are found to correlate with large, collective displacements of the cytoskeletal filaments. We also find that the changes in the localization of tension and the projections of the network motion onto the vibrational normal modes are asymmetrically distributed for energy release and accumulation. These results imply an avalanche-like process of slow energy storage punctuated by fast, large events of energy release involving a collective network rearrangement. We further show that mechanical instability precedes cytoquake occurrence through a machine-learning model that dynamically forecasts cytoquakes using the vibrational spectrum as input. Our results provide a connection between the cytoquake phenomenon and the network’s mechanical energy and can help guide future investigations of the cytoskeleton’s structural susceptibility.

PMID:34611021 | DOI:10.1073/pnas.2110239118

Open Heart. 2021 Oct;8(2):e001785. doi: 10.1136/openhrt-2021-001785.

ABSTRACT

BACKGROUND: COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.

METHODS: A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation.

RESULTS: 242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation.

CONCLUSION: The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.

PMID:34611018 | DOI:10.1136/openhrt-2021-001785

J Knee Surg. 2021 Oct 5. doi: 10.1055/s-0041-1736195. Online ahead of print.

ABSTRACT

Postoperative infections after allograft implantation is a major concern in knee ligament reconstructions considering the theoretical risk of disease transmission and its potential severity. Here, we aimed to evaluate the postoperative infection rate after knee ligament reconstructions using aseptically processed allografts, and provide an overview of the allografts use in an academic tertiary hospital. A retrospective study was performed evaluating patients who underwent knee ligament reconstructions using aseptically processed allografts, including primary and revision surgeries, from 2005 to 2018. Demographic data, including the type of knee injury and trauma energy, and postoperative data were collected focusing on postoperative infections. Regarding these infected cases, further analyses were performed considering the presenting signs and symptoms, the isolated microorganism identified in culture, the time between graft implantation and diagnosis of infection (defined as acute, subacute, and late), and the need for graft removal. A total of 180 cases of ligament reconstructions were included. The mean follow-up was 8.2 (range: 2.1-15.6) years and the mean age at surgery was 34.1 (± 11.1) years. A total of 262 allografts were implanted in those 180 cases, 93 (35.5%) as bone plug allografts and 169 (64.5%) as soft tissue allografts. Common surgical indications included multiligament reconstruction (57.2%) and primary anterior cruciate ligament (ACL) reconstruction (15%). Seven cases (3.9%) presented postoperative infections. Knee pain (100%) and swelling (100%) were the most prevalent symptoms. Two cases (28.6%) presented sinus tract. Allografts were removed in two cases, the same cases that presented draining sinus (p = 0.04). High-energy trauma was the only statistically associated factor for infection (p = 0.04). No significant association between infection and the type of allograft (p > 0.99) or sex (p = 0.35) were observed. Four cases (57.1%) had monomicrobial staphylococcal infections. Based on that, the allograft-related infection rate was 1.7% (the remaining three infected cases). Nonirradiated, aseptically processed allografts have a low postoperative infection rate in knee ligament reconstructions, being a safe alternative for surgeries that require additional source, increased variety, and quantity of grafts.

PMID:34610641 | DOI:10.1055/s-0041-1736195

J Chin Med Assoc. 2021 Oct 4. doi: 10.1097/JCMA.0000000000000629. Online ahead of print.

ABSTRACT

BACKGROUND: Cisplatin-based chemotherapy (CBC) is highly efficacious for advanced cervical cancer; its efficacy can be enhanced by combining with 15 mg/kg (standard dose) bevacizumab (BEV). However, this standard dose is associated with various adverse events. Therefore, in this retrospective study, we analyzed the survival outcomes and adverse events in patients with advanced or recurrent cervical cancer treated with CBC in combination with BEV 7.5 mg/kg.

METHODS: Registered patient data were retrieved between October 2014 and September 2019, and 64 patients with advanced or recurrent cervical cancer treated with CBC+BEV (n=21) or CBC alone (n=43) were analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS); the secondary endpoints were the frequency and severity of adverse events (AEs). The Cox proportional-hazards model was applied to explore prognostic factors associated with PFS and OS.

RESULTS: The 1-, 2-, and 3-year PFS rates (95% confidence interval (CI)) were 36.24% (22.0-50.5), 20.7% (9.8-34.2), and 17.7% (7.7-31.1) for the CBC group; and 71.4% (47.1-86.0), 51.0% (27.9-70.1), and 51.0% (27.9-70.1) for the CBC+BEV group, respectively. The 1-, 2-, and 3-year OS rates were 62.6% (46.4-75.18), 32.4% (18.8-46.9), and 23.2% (11.2-37.6) for the CBC group; and 85.7% (61.9-95.1), 66.6% (42.5-82.5), and 55.5% (27.1-76.7) for the CBC+BEV group, respectively. The CBC+BEV group presented higher PFS and OS rates, p=0.003 and p=0.005, respectively. Proteinuria (6 vs. 9, p=0.025) and hypertension (0 vs. 10, p<0.001) were less common, but anemia was more common in the CBC group (35 vs. 11, p=0.021).

CONCLUSION: Overall, CBC+BEV significantly improved the PFS and OS compared with CBC alone. CBC+BEV also prevents severe adverse events and hence is an efficacious and safe therapeutic option.

PMID:34610623 | DOI:10.1097/JCMA.0000000000000629

Invest Radiol. 2021 Oct 4. doi: 10.1097/RLI.0000000000000829. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to evaluate the diagnostic performance of the maximum intensity projection (MIP) reformations of breast computed tomography (B-CT) images as a stand-alone method for the detection and characterization of breast imaging findings.

MATERIALS AND METHODS: A total of 160 women undergoing B-CT between August 2018 and December 2020 were retrospectively included; 80 patients with known breast imaging findings were matched with 80 patients without imaging findings according to age and amount of fibroglandular tissue (FGT). A total of 71 benign and 9 malignant lesions were included. Images were evaluated using 15-mm MIP in 3 planes by 2 radiologists with experience in B-CT. The presence of lesions and FGT were evaluated, using the BI-RADS classification. Interreader agreement and descriptive statistics were calculated.

RESULTS: The interreader agreement of the 2 readers for finding a lesion (benign or malignant) was 0.86 and for rating according to BI-RADS classification was 0.82. One of 9 cancers (11.1%) was missed by both readers due to dense breast tissue. BI-RADS 1 was correctly applied to 73 of 80 patients (91.3%) by reader 1 and to 74 of 80 patients (92.5%) by reader 2 without recognizable lesions. BI-RADS 2 or higher with a lesion in at least one of the breasts was correctly applied in 69 of 80 patients (86.3%) by both readers. For finding a malignant lesion, sensitivity was 88.9% (95% confidence interval [CI], 51.75%-99.72%) for both readers, and specificity was 99.3% (95% CI, 96.4%-100%) for reader 1 and 100% (95% CI, 97.20%-100.00%) for reader 2.

CONCLUSIONS: Evaluation of B-CT images using the MIP reformations may help to reduce the reading time with high diagnostic performance and confidence.

PMID:34610622 | DOI:10.1097/RLI.0000000000000829

Ther Drug Monit. 2021 Oct 1. doi: 10.1097/FTD.0000000000000927. Online ahead of print.

ABSTRACT

PURPOSE: P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications (ASMs). The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric epileptic patients.

METHODS: The serum concentrations of LCM were determined by ultra-performance liquid chromatography, and the ABCB1 polymorphism was analyzed via polymerase chain reaction-fluorescence staining in situ hybridization. The chi-squared test and Fisher’s exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the One-Way Analysis of Variance (ANOVA) and Mann-Whitney test.

RESULTS: A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (p < 0.05, OR = 1.966, 95% CI = 1.060-3.647). Patients with the G2677T/A- AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 vs 0.8 ± 0.5 μg/ml per mg/kg, p < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (p = 0.008 and p = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (p = 0.042).

CONCLUSION: ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients.

PMID:34610620 | DOI:10.1097/FTD.0000000000000927

Spine (Phila Pa 1976). 2021 Oct 1. doi: 10.1097/BRS.0000000000004244. Online ahead of print.

ABSTRACT

STUDY DESIGN: A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966).

OBJECTIVE: To evaluate the association of lumbosacral transitional vertebrae (LSTV) with low back pain (LBP) and associated degenerative findings using MR imaging.

SUMMARY OF BACKGROUND DATA: LSTV is a common finding with a prevalence of 10% to 29%. LSTV causes biomechanical alterations leading to accelerated lumbar degeneration. However, its association with degenerative findings on MRI and LBP is unclear.

METHODS: 1468 lumbar spine MRI scans from the NFBC1966 acquired at a mean age of 47 years were assessed for the presence of LSTV and degenerative changes. Castellvi classification was utilized to identify LSTV anatomy. Additionally, 100 controls without LSTV were collected. Self-reported LBP with a duration of >30 days in the past year was deemed clinically relevant. For the statistical analyses, chi square test, independent samples t-test and multinomial logistic regression analyses were used.

RESULTS: LSTV was found in 310 (21.1%) subjects. After adjusting for age, sex and disc degeneration (DD) sum, subjects with Castellvi type III reported prolonged LBP significantly more frequently than the controls (OR = 8.9, p = 0.001). We observed a higher prevalence of facet degeneration (FD) at all levels from L3/L4 to L5/S1 in type I, and L3/L4 to L4/L5 in types II-IV. DD was more prevalent at L4/L5 in types II-IV. Disc protrusion/extrusion occurred more frequently at L3/L4 and L4/L5 in type II, and at L3/L4 in type III. Castellvi type II had a higher prevalence of type 1 Modic changes at all levels from L3/L4 to L5/S1, and type IV had a higher prevalence of any Modic changes at L4/L5.

CONCLUSION: LSTVs were a common finding within this study, and Castellvi type III LSTVs were associated with LBP. Degenerative findings were associated with LSTV anatomy and occurred more commonly above the transitional level.Level of Evidence: 3.

PMID:34610612 | DOI:10.1097/BRS.0000000000004244