Category: Statistics

J Viral Hepat. 2021 Aug 31. doi: 10.1111/jvh.13606. Online ahead of print.

ABSTRACT

Hepatitis B viral (HBV) load and hepatic enzymes play a critical role in hepatocellular carcinoma (HCC) development. The clinical significance of both in HBV-related HCC patients after hepatectomy remains unclear. This study analyzed 1940 HBV-related HCC patients who underwent hepatectomy from four hospitals in west China. Risk classification was constructed based on baseline HBV-DNA level and AST/ALT ratio. Based on the HBV-DNA and AST/ALT ratio classification, four types with distinguishable prognosis were established. Type 1 patients had best prognosis with 69.8% 5-year overall survival (OS), while the type 4 patients had worst prognosis with 42.7% 5-year OS, type 3 and type 2 patients followed. Similarly, the four subgroups had statistically different recurrence free survival (RFS). This classification was significantly associated with HCC recurrence (hazard ratio [HR]:1.492, p<0.001) and long-term survival (HR:1.574, p=0.001). Pathologically, Type 4 correlated with more advanced tumors, such as tumor size and microvascular invasion (vs. type 1/2/3). Moreover, type 4 patients had more severe hepatic inflammation in underlying liver. Conversely, type 1 had active tumor immune microenvironment indicated by more CD8+ T cell infiltration and less PD-L1 expression. In conclusion, baseline HBV-DNA and AST/ALT ratio classification could effectively stratify HBV-related HCC patients with distinguishable prognosis after hepatectomy.

PMID:34464991 | DOI:10.1111/jvh.13606

Cancer Sci. 2021 Aug 31. doi: 10.1111/cas.15126. Online ahead of print.

ABSTRACT

Fusobacterium nucleatum has been detected in 8-13% of human colorectal cancer, and shown to inhibit immune responses against primary colorectal tumours in animal models. Thus, we hypothesised that the presence of F. nucleatum might be associated with reduced T-cell density in colorectal cancer liver metastases (CRLMs). We quantified F. nucleatum DNA in 181 CRLM specimens using quantitative polymerase chain reaction assay. The densities of CD8⁺ T cells, CD33⁺ cells (marker for myeloid-derived suppressor cells (MDSCs)), and CD163⁺ cells (marker for tumour-associated macrophages (TAMs)) in CRLM tissue were determined by immunohistochemical staining. F. nucleatum was detected in eight (4.4%) of 181 CRLM specimens. Compared with F. nucleatum-negative CRLMs, F. nucleatum-positive CRLMs exhibited significantly lower density of CD8⁺ T cells (P = 0.033) and higher density of MDSCs (P = 0.001). The association of F. nucleatum with the density of TAMs was not statistically significant (P = 0.70). The presence of F. nucleatum is associated with a lower density of CD8⁺ T cells and a higher density of MDSCs in CRLM tissue. Upon validation, our findings may provide insights to develop strategies that involve targeting microbiota and immune cells for the prevention and treatment of CRLMs.

PMID:34464993 | DOI:10.1111/cas.15126

Mol Biol Evol. 2021 Aug 31:msab243. doi: 10.1093/molbev/msab243. Online ahead of print.

ABSTRACT

A nonsense allele at rs1343879 in human MAGEE2 on chromosome X has previously been reported as a strong candidate for positive selection in East Asia. This premature stop codon causing ∼80% protein truncation is characterized by a striking geographical pattern of high population differentiation: common in Asia and the Americas (up to 84% in the 1000 Genomes Project East Asians) but rare elsewhere. Here, we generated a Magee2 mouse knockout mimicking the human loss-of-function mutation to study its functional consequences. The Magee2 null mice did not exhibit gross abnormalities apart from enlarged brain structures (13% increased total brain area, P = 0.0022) in hemizygous males. The area of the granular retrosplenial cortex responsible for memory, navigation and spatial information processing was the most severely affected, exhibiting an enlargement of 34% (P = 3.4×10-6). The brain size in homozygous females showed the opposite trend of reduced brain size, although this did not reach statistical significance. With these insights, we performed human association analyses between brain size measurements and rs1343879 genotypes in 141 Chinese volunteers with brain MRI scans, replicating the sexual dimorphism seen in the knockout mouse model. The derived stop gain allele was significantly associated with a larger volume of grey matter in males (P = 0.00094), and smaller volumes of grey (P = 0.00021) and white (P = 0.0015) matter in females. It is unclear whether or not the observed neuroanatomical phenotypes affect behaviour or cognition, but it might have been the driving force underlying the positive selection in humans.

PMID:34464968 | DOI:10.1093/molbev/msab243

J Stroke Cerebrovasc Dis. 2021 Jun 18;30(11):105953. doi: 10.1016/j.jstrokecerebrovasdis.2021.105953. Online ahead of print.

ABSTRACT

Background and purpose; Chile has been one of the most affected countries by the COVID-19 pandemic, with one of the highest case rates per population. This has affected the epidemiological behaviour of various pathologies. We analyze the impact of the pandemic on the number of admissions due to stroke, its severity and mortality in Santiago, Chile.

METHODS: a multicenter observational study based on the records of the 3 hospitals of the South East health service in Santiago, Chile. We recorded the number of patients admitted for ischemic stroke between 01 January 2020 and 30 June 2020. We grouped the cases into two periods, pre-pandemic and pandemic, according to the setting of the state of emergency in Chile.

RESULTS: 431 patients were admitted with ischemic stroke during the study period. There was a non-significant decrease in weekly admissions (17 vs 15 patients per week). No differences were observed in the proportion of patients with medical treatment (p = 0.810), IVT (p = 0.638), EVT (p = 0.503) or IVT + EVT (p = 0.501). There was a statistically significant increase in the NIHSS on admission (7.23 vs 8.78, p = 0.009) and mortality (5.2% vs 12.4%, p = 0.012). In a multivariate analysis the NIHSS on admission was associated with the increased mortality (RR 1.11, CI 1.04-1.19, p = 0.003).

CONCLUSION: We found an increase in the severity of ischemic stroke on admission and in-hospital mortality during the pandemic period. The main factor to increase in-hospital mortality was the NIHSS on admission.

PMID:34464928 | DOI:10.1016/j.jstrokecerebrovasdis.2021.105953

Eur J Radiol. 2021 Aug 26;143:109936. doi: 10.1016/j.ejrad.2021.109936. Online ahead of print.

ABSTRACT

PURPOSE: To compare the image quality, presence of artifacts and apparent diffusion coefficient (ADC) values of reduced field-of-view (rFOV) and large FOV (lFOV) single-shot spin-echo echo-planar diffusion-weighted imaging (DWI) in the evaluation of solid pancreatic lesion.

METHOD: The 3T MR examinations of 60 patients with solid pancreatic lesions were examined. Two Readers independently performed qualitative analysis and quantitative measurements of the ADC values of the solid pancreatic lesions in both rFOV and lFOV DWI sequence. The qualitative analysis parameters included: 1) Sharpness, 2) Distortion, Ghosting, Motion and Susceptibility artifacts, 3) Lesion Conspicuity and 4) Overall Image Quality. These parameters were evaluated using a 4-point scale. The T-test for paired data was used to compare qualitative scores and the ADC values of the rFOV and lFOV DWI sequences, and to assess inter-reader agreement.

RESULTS: The qualitative analysis yielded scores for the rFOV DWI sequence, which were better for sharpness, artifacts, and overall image quality as compared to the lFOV DWI sequence according to the only Reader 2 (the most experienced) (p ≤ 0.001). As to lesion conspicuity, no significant difference was found by either Reader (p ≥ 0.245). As to quantitative analysis, both Readers found no significant difference between the two sequences in the ADC values of various solid pancreatic lesions (p ≥ 0.156).

CONCLUSIONS: The rFOV DWI sequence of the pancreas provides better anatomic structure visualization, reduced artifacts, and better overall image quality as compared to the lFOV DWI sequence according to the Reader with the more experience in abdominal MRI. The ADC values were not significantly different in the two sequences. The rFOV DWI sequence could be included in the standard MRI protocol for the pancreas.

PMID:34464906 | DOI:10.1016/j.ejrad.2021.109936

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Aug 6;264:120255. doi: 10.1016/j.saa.2021.120255. Online ahead of print.

ABSTRACT

For the estimation of some co-administered antimicrobials, two highly accurate and precise spectrofluorimetric methods were developed. Fluconazole (FLZ) is co-administered with either ciprofloxacin (CPR) or ofloxacin (OFX) for the treatment of certain microbial infections. On the other hand, another antimicrobial drug, vancomycin (VNC) is co-administered with ciprofloxacin (CPR) for peritonitis treatment. In method I, conventional spectrofluorimetry has been introduced for the concurrent quantitative estimation of FLZ in presence of OFX or CPR. While in method II, a first derivative synchronous spectrofluorimetric technique was adapted for quantitation of VNC and CPR co-administered combination. Both of them were utilized for estimation of the considered drugs in raw materials, laboratory prepared mixtures, dosage forms, and biological fluids. Method I was relied on simultaneous measuring of the native fluorescence of FLZ and OFX or CPR without any overlapping between the emission spectra of each binary mixture (FLZ / OFX) and (FLZ / CPR). Fluorescence intensities were measured at 283.0, 483.0 and 436.0 nm after excitation at 262.0, 292.0 and 275.0 nm for FLZ, OFX and CPR, respectively. Method II was utilized the synchronous fluorescence intensity of VNC and CPR in methanol at Δλ = 40 nm. The first derivative synchronous spectra were calibrated at 297.0 nm for VNC and at 379.5 nm for CPR. Different variables influencing conventional and synchronous fluorescence intensities of the four antimicrobials under investigation were precisely optimized. Both methods were successfully investigated for the determination of the studied drugs in plasma. The linear data analysis for the calibration curves reveals a good relationship in the ranges of 1.0-10.0, 0.25-2.5 and 0.06-0.6 μg/mL for FLZ, OFX and CPR for method I with limits of detection 0.144, 0.038 and 0.007 μg/mL and limits of quantitation of 0.437, 0.114 and 0.021 μg/mL for FLZ, OFX and CPR, respectively. Linearity range for method II was 0.5 -10.0 μg/mL for VNC and CPR with detection limits of 0.127 and 0.110 μg/mL and quantitation limits of 0.380 and 0.334 μg/mL for VNC and CPR, respectively. International Council on Harmonization ICH Q2 (R1) Guidelines were followed in the developed methods validation. The achieved outcomes were statistically compared with those found by the reported ones, and no significant difference was observed.

PMID:34464919 | DOI:10.1016/j.saa.2021.120255

J Infect Public Health. 2021 Aug 24;14(9):1247-1253. doi: 10.1016/j.jiph.2021.08.022. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the efficacy of Favipiravir compared to the standard therapy in treating patients with severe COVID-19 infection.

METHODS: This is a retrospective cohort of patients with COVID-19 pneumonia who were treated with favipiravir, versus comparison group that received the standard of care.

RESULTS: A total of 226 patients were included; 110 patients received favipiravir and 116 patients received standard of care. Patients who received favipiravir had longer time to recovery (14.2 ± 8.8 versus 12.8 ± 5.2, p = 0.17). Favipiravir was associated with an improved early day 14 mortality (4 [3.6%] versus 11 [9.5%]), p = 0.008), but was associated with a higher day 28 mortality (26 [23.6%] versus 11 [9.5%], p = 0.02). The overall mortality was higher in the favipiravir versus the standard of care group but difference was not statistically significant (33 [30.0%] versus 24 [20.7%], p = 0.10).

CONCLUSION: The addition of favipiravir to standard of care was not associated with any improvement in clinical outcomes or mortality. Larger randomized controlled clinical trials are needed to further assess the efficacy of favipiravir.

PMID:34464921 | DOI:10.1016/j.jiph.2021.08.022

J Surg Res. 2021 Aug 28;268:562-569. doi: 10.1016/j.jss.2021.06.076. Online ahead of print.

ABSTRACT

BACKGROUND: Thyroid nodules are common; up to 67% of adults will show nodules on high-quality ultrasound, and 95% of these nodules are benign. FNA cytology is a crucial step in determining the risk of malignancy, and a false negative diagnosis at this stage delays cancer treatment. The purpose of this study is to develop a predictive model using machine learning which can identify false negative FNA results based on less-invasive clinical data.

MATERIALS AND METHODS: We conducted a retrospective medical record review at one academic and one community center. Inclusion criteria were thyroid nodules evaluated by ultrasound and FNA with a Bethesda II (benign) result or malignancy detected on pathology or FNA. Linear, non-linear, and ensemble models were generated with scikit-learn using 10-fold cross validation with repetition and compared with AUROC. The classification task was the prediction of malignancy using information acquired from less-invasive ultrasound and FNA.

RESULTS: A total of 604 subjects met inclusion criteria; 38 were diagnosed with malignancy. Of all algorithms tested, a Random Forest method achieved the best AUROC (0.64) in separating benign and malignant nodules, though the improvement over other tested algorithms was not statistically significant.

CONCLUSIONS: A Random Forest model performed better than random chance using readily available data obtained via standard evaluation of thyroid nodules. The diagnostic probability threshold of this model can be varied to minimize false positives at the cost of increasing the number of false negatives. Future studies will prospectively evaluate the model’s performance.

PMID:34464894 | DOI:10.1016/j.jss.2021.06.076

J Surg Res. 2021 Aug 28;268:595-605. doi: 10.1016/j.jss.2021.07.014. Online ahead of print.

ABSTRACT

BACKGROUND: Timely identification and management of sepsis in surgical patients is crucial, and transfer status may delay optimal treatment of these patients. The objective of this study was to compare in-house and 90-day mortality between patients primarily admitted or transferred into the surgical ICU (SICU) at a tertiary referral center.

MATERIAL AND METHODS: All patients admitted to the SICU with a diagnosis of sepsis (Sepsis III) were reviewed at a single institution between 2014 to 2019 (n = 1489). Demographics, comorbidities, and sepsis presentation were compared between transferred (n = 696) and primary patients (n = 793). Primary outcomes evaluated were in-house and 90 day mortality in an unmatched and propensity score matched cohorts. A P value < 0.05 was considered statistically significant.

RESULTS: Transfer patients were more likely to have obesity (60% versus 49%, P < 0.005), a higher median SOFA (6 (4-8) versus 5 (3-8), P = 0.007), and require vasopressors on admission (42% versus 35%, P = 0.004). Compared to primary patients, transfer patients exhibited higher rates of respiratory failure (76% versus 69%, P = 0.003), in-house (30% versus 17%, P < 0.005), and 90 day mortality (36% versus 24%, P < 0.005). After matching, transferred patients were associated with 75% and 83% increased odds of in-house and 90 day mortality after controlling for age, sex, race, comorbidities, BMI, and sepsis severity.

CONCLUSIONS: Transfer status is associated with an over 80% increase in the odds of 90 day mortality for patients admitted to the SICU with sepsis. Aggressive patient identification and earlier transfer of those at higher risk of death may reduce this effect.

PMID:34464897 | DOI:10.1016/j.jss.2021.07.014

Accid Anal Prev. 2021 Aug 28;161:106357. doi: 10.1016/j.aap.2021.106357. Online ahead of print.

ABSTRACT

It is widely believed that with higher levels of vehicle automation and especially with the advent of fully automatic vehicles, the currently typical forward-facing, upright position will give way to a more relaxed and reclined seating posture. Therefore, the current study investigates the influence of a reclined sitting position on crash injury severity by analyzing real-world crash data from the German in-depth accident study (GIDAS). We compared reclined to upright occupants and focused on effect sizes regarding odds ratios at different injury severity levels. We used the abbreviated injury scale (AIS 2015) for injury scaling and the maximum AIS (MAIS) at the levels 2+, 3+, and 4+ to convert injury severity into a dichotomous metric. Two different analyses were conducted, one looking at the occupant MAIS and one focusing on selected body regions. The body regions investigated are head/face/neck (HFN), thorax, abdomen, pelvis/hip/lower extremities (PHL), and upper extremities. We computed odds ratios greater than one indicating a higher odds of injury at a given injury severity level in the reclined group compared to the upright group. The odds ratios for belted, reclined occupants compared to belted, upright sitting occupants are 2.07, 3.09, and 3.66 for the injury severity levels MAIS2+, MAIS3+, and MAIS4+, respectively. When looking at the body regions, the spread of the odds ratios is wider: At the MAIS2+ level, the odds ratios range between 1.6 and 7.1; at the MAIS3+ level, the odds ratios span from 1.5 to 8.7, with the latter value representing the PHL region. No odds ratio could be computed for the upper extremity injuries at this level. At the MAIS4+ injury severity level, only the HFN odds ratio was statistically significant with a value of 5.6. This study is among the first to show an association between body posture and injury severity at MAIS3+ and MAIS4+ injury level in real-world crashes for reclined seating postures.

PMID:34464840 | DOI:10.1016/j.aap.2021.106357