Nevin Manimala

Arch Orthop Trauma Surg. 2022 Jul 2. doi: 10.1007/s00402-022-04530-1. Online ahead of print.

ABSTRACT

INTRODUCTION: High body mass index (BMI) and wound drainage following total joint arthroplasty (TJA) can lead to wound healing complications and periprosthetic joint infection. Silver-embedded occlusive dressings and negative pressure wound therapy (NPWT) have been shown to reduce these complications. The purpose of this prospective trial was to compare the effect of silver-embedded dressings and NPWT on wound complications in patients with BMI ≥ 35 m/kg2 undergoing TJA.

METHODS: We conducted a randomized control trial of patients who had a BMI > 35 m/kg² and were undergoing primary TJA between October 2017 and February 2020. Patients who underwent revision surgery, or those with an active infection, previous scar, history of wound healing complications, post-traumatic degenerative joint disease with hardware, or inflammatory arthritis were excluded. Patients were randomized to receive either a silver-embedded occlusive dressing (control) or NPWT. Frequency distributions, means, and standard deviations were used to describe patient demographics, postoperative complications, 90-day readmissions, and reoperations. T-test and chi-squared tests were used to test for significant differences between continuous and categorical variables, respectively.

RESULTS: Two hundred-thirty patients with 3-month follow-up were included. One-hundred-fifteen patients received the control and 115 patients received NPWT. There were six patients (5.2%) in the control group with wound complications (drainage: n = 5, non-healing wound: n = 1) and two patients (1.7%) in the NPWT with complications (drainage: n = 2). There were no 90-day readmissions in the control group versus two (1.8%) 90-day readmissions in the NPWT group. Finally, three patients (2.6%) in the control group underwent reoperations (irrigation and debridement [I&D], I&D with modular implant exchange, and implant revision), while none in the NPWT group had undergone reoperation. The two groups showed insignificant differences in wound complications (p = 0.28), 90-day readmissions (p = 0.50), and reoperations (p = 0.25).

CONCLUSION: Patients with BMI ≥ 35 m/kg2 undergoing TJA have no statistical difference in early wound complications, readmissions, or reoperations when treated with either silver-embedded dressings or NPWT.

PMID:35779102 | DOI:10.1007/s00402-022-04530-1

Eur Radiol. 2022 Jul 2. doi: 10.1007/s00330-022-08934-w. Online ahead of print.

ABSTRACT

OBJECTIVES: To provide a standard for total abdominal muscle mass (TAM) quantification on computed tomography (CT) and investigate its association with cardiovascular risk in a primary prevention setting.

METHODS: We included 3016 Framingham Heart Study participants free of cardiovascular disease (CVD) who underwent abdominal CT between 2002 and 2005. On a single CT slice at the level of L3/L4, we segmented (1) TAM-Area, (2) TAM-Index (= TAM-Area/height) and, (3) TAM-Fraction (= TAM-Area/total cross-sectional CT-area). We tested the association of these muscle mass measures with prevalent and incident cardiometabolic risk factors and incident CVD events during a follow-up of 11.0 ± 2.7 years.

RESULTS: In this community-based sample (49% women, mean age: 50.0 ± 10.0 years), all muscle quantity measures were significantly associated with prevalent and incident cardiometabolic risk factors and CVD events. However, only TAM-Fraction remained significantly associated with key outcomes (e.g., adj. OR 0.68 [0.55, 0.84] and HR 0.73 [0.57, 0.92] for incident hypertension and CVD events, respectively) after adjustment for age, sex, body mass index, and waist circumference. Moreover, only higher TAM-Fraction was associated with a lower risk (e.g., adj. OR: 0.56 [0.36-0.89] for incident diabetes versus TAM-Area: adj. OR 1.26 [0.79-2.01] and TAM-Index: 1.09 [0.75-1.58]).

CONCLUSION: TAM-Fraction on a single CT slice at L3/L4 is a novel body composition marker of cardiometabolic risk in a primary prevention setting that has the potential to improve risk stratification beyond traditional measures of obesity.

KEY POINTS: • In this analysis of the Framingham Heart Study (n = 3016), TAM-F on a single slice CT was more closely associated with prevalent and incident cardiometabolic risk factors as compared to TAM alone or TAM indexed to body surface area. • TAM-F on a single abdominal CT slice at the level of L3/L4 could serve as a standard measure of muscle mass and improve risk prediction.

PMID:35779090 | DOI:10.1007/s00330-022-08934-w

Eur Radiol. 2022 Jul 2. doi: 10.1007/s00330-022-08969-z. Online ahead of print.

ABSTRACT

OBJECTIVES: While chest radiograph (CXR) is the first-line imaging investigation in patients with respiratory symptoms, differentiating COVID-19 from other respiratory infections on CXR remains challenging. We developed and validated an AI system for COVID-19 detection on presenting CXR.

METHODS: A deep learning model (RadGenX), trained on 168,850 CXRs, was validated on a large international test set of presenting CXRs of symptomatic patients from 9 study sites (US, Italy, and Hong Kong SAR) and 2 public datasets from the US and Europe. Performance was measured by area under the receiver operator characteristic curve (AUC). Bootstrapped simulations were performed to assess performance across a range of potential COVID-19 disease prevalence values (3.33 to 33.3%). Comparison against international radiologists was performed on an independent test set of 852 cases.

RESULTS: RadGenX achieved an AUC of 0.89 on 4-fold cross-validation and an AUC of 0.79 (95%CI 0.78-0.80) on an independent test cohort of 5,894 patients. Delong’s test showed statistical differences in model performance across patients from different regions (p < 0.01), disease severity (p < 0.001), gender (p < 0.001), and age (p = 0.03). Prevalence simulations showed the negative predictive value increases from 86.1% at 33.3% prevalence, to greater than 98.5% at any prevalence below 4.5%. Compared with radiologists, McNemar’s test showed the model has higher sensitivity (p < 0.001) but lower specificity (p < 0.001).

CONCLUSION: An AI model that predicts COVID-19 infection on CXR in symptomatic patients was validated on a large international cohort providing valuable context on testing and performance expectations for AI systems that perform COVID-19 prediction on CXR.

KEY POINTS: • An AI model developed using CXRs to detect COVID-19 was validated in a large multi-center cohort of 5,894 patients from 9 prospectively recruited sites and 2 public datasets. • Differences in AI model performance were seen across region, disease severity, gender, and age. • Prevalence simulations on the international test set demonstrate the model’s NPV is greater than 98.5% at any prevalence below 4.5%.

PMID:35779089 | DOI:10.1007/s00330-022-08969-z

Rheumatol Int. 2022 Jul 2. doi: 10.1007/s00296-022-05164-7. Online ahead of print.

ABSTRACT

There are limited data about humoral response to vaccine in Behçet’s syndrome (BS). We compared SARS-CoV-2 antibody response after two doses of inactivated (Sinovac/CoronaVac) or mRNA (Pfizer/BioNTech) vaccines in patients with BS and healthy controls (HCs). We studied 166 (92M/74F) patients with BS (mean age: 42.9 ± 9.6 years) and 165 (75M/90F) healthy controls (mean age: 42.4 ± 10.4 years), in a single-center cross-sectional design between April 2021 and October 2021. A total of 80 patients with BS and 89 HCs received two doses of CoronaVac, while 86 patients with BS and 76 HCs were vaccinated with BioNTech. All study subjects had a negative history for COVID-19. Serum samples were collected at least 21 days after the second dose of the vaccine. Anti-spike IgG antibody titers were measured quantitatively using a commercially available immunoassay method. We found that the great majority in both patient and HC groups had detectable antibodies after either CoronaVac (96.3% vs 100%) or BioNTech (98.8% vs 100%). Among those vaccinated with CoronaVac, BS patients had significantly lower median (IQR) titers compared to HCs [36.5 (12.5-128.5) vs 102 (59-180), p < 0.001]. On the other hand, antibody titers did not differ among patients with BS and HCs who were vaccinated with BioNTech [1648.5 (527.0-3693.8) vs 1516.0 (836.3-2599.5), p = 0.512). Among different treatment regimen subgroups in both vaccine groups, those who were using anti-TNF-based treatment had the lowest antibody titers. However, the difference was statistically significant only among those vaccinated with CoronaVac. Among patients vaccinated with BioNTech, there was no statistically significant difference between different treatment regimen groups. Compared to inactivated COVID-19 vaccine, mRNA-based vaccine elicited higher antibody titers among BS patients. Only in the CoronaVac group, patients especially those using anti-TNF agents were found to have low titers compared to healthy subjects. BS patients vaccinated with BioNTech were found to have similar seroconversion rates and antibody levels compared to healthy controls. Further studies should assess whether the low antibody titers are associated with diminished protection against COVID-19 in both vaccine groups.

PMID:35779083 | DOI:10.1007/s00296-022-05164-7

Int J Colorectal Dis. 2022 Jul 2. doi: 10.1007/s00384-022-04206-7. Online ahead of print.

ABSTRACT

PURPOSE: To determine the results after rectovaginal fistula (RVF) repair and find predictors of outcome. Primary objective was fistula healing. Secondary outcomes were morbidity and patient health-related quality of life (HRQoL).

METHOD: An observational study of 55 women who underwent RVF repair including both local procedures and tissue transposition 2003-2018 was performed. Baseline patient and fistula characteristics were registered, combined with a prospective HRQoL follow-up and a general questionnaire describing fistula symptoms.

RESULTS: Healing rate after index surgery was 25.5% (n = 14) but the final healing rate was 67.3% (n = 37). Comparing the etiologies, traumatic fistulas (iatrogenic and obstetric) had the highest healing rates after index surgery (n = 11, 45.9%) and after repeated operations at final follow-up (n = 22, 91.7%) compared with fistulas of inflammatory fistulas (Crohn’s disease, cryptoglandular infection, and anastomotic leakage) that had inferior healing rates after both index surgery (n = 7, 7.1%) and at final follow-up (n = 13, 46.4%). Fistulas of the category others (radiation damage and unknown etiology) included a small amount of patients with intermediate results at both index surgery (n = 1, 33.3%) and healing rate at last follow-up (n = 2, 66.7%). The differences were statistically significant for both index surgery (p = 0.004) and at final follow-up (p = 0.001). Unhealed patients scored lower than both healed patients and the normal population in 6/8 Rand-36 domains, but the differences were not statistically significant.

CONCLUSIONS: Most traumatic rectovaginal fistulas closed after repeated surgery whereas inflammatory fistulas had a poor prognosis. Low healing rates after local repairs suggest that tissue transfer might be indicated more early in the treatment process. Unhealed fistulas were associated with reduced quality of life. Trial registration Clinicaltrials.gov No. NCT05006586.

PMID:35779081 | DOI:10.1007/s00384-022-04206-7

J Med Philos. 2022 Jul 2:jhac001. doi: 10.1093/jmp/jhac001. Online ahead of print.

ABSTRACT

The status of risk factors and disease remains a disputed question in the theory and practice of medicine and healthcare, and so does the related question of delineating disease boundaries. I present a framework based on Bernard Lonergan’s account of emergent probability for differentiating (1) generically distinct levels of systematic function within organisms and between organisms and their environments and (2) the methods of functional, genetic, and statistical investigation. I then argue on this basis that it is possible to understand disease in terms of biological or higher intra-level dysfunction, risk factors-including genetic risk factors-in terms of statistical inter-level conditioning of a given stage or developmental sequence of systematic functioning, and the empirical boundaries of disease in terms of the limits of both functional categorization (from an epistemic standpoint) and upper-level integration of lower-level processes and events (from an ontological standpoint).

PMID:35779075 | DOI:10.1093/jmp/jhac001

ANZ J Surg. 2022 Jul 2. doi: 10.1111/ans.17896. Online ahead of print.

ABSTRACT

BACKGROUND: Stage III colorectal cancer (CRC), which accounts for approximately one third of all CRC cases, is associated with worsened prognosis. The aim of this study was to compare the preoperatively measured systemic inflammatory markers and to define the most significant marker in terms of its prognostic value in stage III CRC.

METHODS: Surgically treated stage III CRC patients were included. Demographics, preoperatively measured Glasgow prognostic score (GPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/C-reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) values, clinicopathological features, surgical, oncological and survival outcomes were recorded and statistically analysed.

RESULTS: The study group of 102 patients consisted of 65 (63.7%) men and 37 (36.3%) women with a median age of 64 (range: 26-89). The mean follow-up period was 42.8 ± 30.5 (range: 6-107) months. Overall survival (OS) and disease-free survival (DFS) rates were 71.6%, and 67.7%, respectively. Elevated CRP, GPS 2, LCR ≤ 0.530, CAR ≥ 0.080, higher numbers of metastatic lymph nodes and N2b nodal status were detected to impair DFS (P = 0.001, P = 0.015, P = 0.001, P = 0.001, P = 0.001 and P = 0.043, respectively). Variables including GPS 2, PLR≥190.83, CAR≥0.045, LCR≤0.684, surgical site infection and longer hospital stay decreased OS (P = 0.004, P = 0.002, P = 0.005, P = 0.001, P = 0.001 and P = 0.001, respectively). According to multivariate analysis; PLR ≥ 190.83 was associated with three times [HR: 2.892 (95% CI: 1.100-7.602), P = 0.031], and LCR ≤ 0.684 was associated with four times [HR: 3.919 (95% CI: 1.130-13.592), P = 0.031] greater risk of cancer-related mortality.

CONCLUSION: As an independent prognostic factor, LCR had the highest impact on predicting survival after curative resection for stage III CRC.

PMID:35779019 | DOI:10.1111/ans.17896

J Obstet Gynaecol Res. 2022 Jul 2. doi: 10.1111/jog.15344. Online ahead of print.

ABSTRACT

AIM: This study aimed to present the contribution of prenatal magnetic resonance imaging (MRI) in the diagnosis of fetuses that were previously identified as isolated mild and moderate cerebral ventriculomegaly (VM) by ultrasound (US).

METHODS: The data between February 2013 and August 2020 were collected for women who were diagnosed with isolated mild or moderate fetal VM by US and subsequently underwent a fetal MRI.

RESULTS: Among 321 women, 21 (6.5%) had a clinically important additional finding after MRI. Twelve of 276 (4.3%) fetuses with mild VM and 9 of 45 (20%) with moderate VM had turned out to have additional central nervous system abnormalities. Additional findings were detected more in fetuses with moderate VM, mothers with an anterior-located placenta, and mothers with higher body mass indexes (BMIs) with statistical significance (p = 0.001, p = 0.013, p = 0.036, respectively). The most common additional MRI finding was grade 3 or 4 germinal matrix hemorrhage, which was detected in 11 of 21 fetuses (52.3%).

CONCLUSIONS: Considering the countries’ health policies, prenatal MRI would contribute mostly to the diagnosis of fetuses with moderate VM, pregnancies with anterior-located placenta, and mothers with high BMIs. According to our data, we believe that MRI will be valuable, especially in the diagnosis of grade 3 and 4 intracranial hemorrhage group.

PMID:35778980 | DOI:10.1111/jog.15344

Clin Pharmacol Drug Dev. 2022 Jul 2. doi: 10.1002/cpdd.1135. Online ahead of print.

ABSTRACT

This study aimed to evaluate the pharmacokinetics (PK), safety, and immunogenicity of the infliximab biosimilar CMAB008 compared to the reference product (Remicade) in healthy Chinese male subjects to provide the basis for the similarity evaluation of the 2 drugs. In this phase I randomized, double-blind, parallel-controlled, single-dose study, a total of 90 subjects were randomized 1:1 to receive CMAB008 or infliximab reference product with single intravenous injections (5 mg/kg). Blood samples were collected at designed time points for PK and immunogenicity assessment. If the 90%CI of the geometric mean ratio of area under the plasma concentration-time curve from 0 to the time of the last observation, maximum observed plasma concentration, area under the plasma concentration-time curve from 0 to infinity was completely within the range of 80% to 125%, the PK bioequivalence was established. Other PK parameters including time to maximum plasma concentration_, half-life time, clearance, apparent volume of distribution, and last measurable concentration time point were also assessed. Adverse events (AEs) were recorded. Serum concentration-time profiles were similar across the 2 groups, and PK parameters were comparable in the 2 groups. The 90%CI of the geometric mean ratio of test to reference was within the predefined bioequivalence range of 80% to 125%. The AEs occurred similarly in 2 groups. One serious AE (rhabdomyolysis, grade 3) occurred in the test group. The total positive rates of antidrug antibody and neutralizing antibodies in the test group (85.7% and 5.6%, respectively) were numerically lower than infliximab reference product group (90.9% and 15%, respectively). The PK profile of the 2 groups is statistically equivalent. The preliminary safety and immunogenicity evaluation of the 2 drugs are comparable.

PMID:35778977 | DOI:10.1002/cpdd.1135

Clin Chem Lab Med. 2022 Jul 4. doi: 10.1515/cclm-2022-0415. Online ahead of print.

ABSTRACT

OBJECTIVES: Automated machine learning (AutoML) tools can help clinical laboratory professionals to develop machine learning models. The objective of this study was to develop a novel formula for the estimation of urine osmolality using an AutoML tool and to determine the efficiency of AutoML tools in a clinical laboratory setting.

METHODS: Three hundred routine urinalysis samples were used for reference osmolality and urine clinical chemistry analysis. The H2O AutoML engine completed the machine learning development steps with minimum human intervention. Four feature groups were created, which include different urinalysis measurements according to the Boruta feature selection algorithm. Method comparison statistics including Spearman correlation, Passing-Bablok regression analysis were performed, and Bland Altman plots were created to compare model predictions with the reference method. The minimum allowable bias (24.17%) from biological variation data was used as the limit of agreement.

RESULTS: The AutoML engine developed a total of 183 ML models. Conductivity and specific gravity had the highest variable importance. Models that include conductivity, specific gravity, and other urinalysis parameters had the highest R² (0.70-0.83), and 70-84% of results were within the limit of agreement.

CONCLUSIONS: Combining urinary conductivity with other urinalysis parameters using validated machine learning models can yield a promising surrogate. Additionally, AutoML tools facilitate the machine learning development cycle and should be considered for developing ML models in clinical laboratories.

PMID:35778953 | DOI:10.1515/cclm-2022-0415