Nevin Manimala

Appl Immunohistochem Mol Morphol. 2022 Nov 1. doi: 10.1097/PAI.0000000000001084. Online ahead of print.

ABSTRACT

BMP-2 and Noggin are expressed in several tissues and participate in cell differentiation and proliferation during odontogenesis and tumor development. We evaluated the immunohistochemical expression of these proteins in ameloblastomas (AMs), odontogenic keratocysts (OKCs), and dentigerous cysts (DCs). The expression in AM (n.20), OKC (n.20), and DC (n.20) was evaluated by the percentage of positive cells and expression intensity, resulting in a total immunostaining score. Analysis of BMP-2 and Noggin revealed positivity in all cases. The Mann-Whitney test showed a statistically significant difference for Noggin between AM and DC and between OKC/DC. The mean DC scores were always higher than those of the other groups, regardless of the assessment method. Individual analysis of each lesion showed a positive and significant correlation between the percentage of cells positive for BMP-2 and Noggin in DC. We demonstrated the presence of BMP-2 and Noggin in AMs/OKCs/DCs. Marked expression of BMP-2 was observed in OKCs and AMs. There was also a positive correlation between BMP-2 and Noggin in DCs, suggesting a greater role of these markers in the bone formation and remodeling process since DCs are characterized by phases of bone quiescence and healing.

PMID:36315234 | DOI:10.1097/PAI.0000000000001084

J Magn Reson Imaging. 2022 Oct 31. doi: 10.1002/jmri.28509. Online ahead of print.

ABSTRACT

BACKGROUND: The measurement of the concentration of theranostic agents in vivo is essential for the assessment of their therapeutic efficacy and their safety regarding healthy tissue. To this end, there is a need for quantitative T₁ measurements that can be obtained as part of a standard clinical imaging protocol applied to tumor patients.

PURPOSE: To generate T₁ maps from MR images obtained with the magnetization-prepared rapid gradient echo (MPRAGE) sequence. To evaluate the feasibility of the proposed approach on phantoms, animal and patients with brain metastases.

STUDY TYPE: Pilot.

PHANTOM/ANIMAL MODEL/POPULATION: Solutions containing contrast agents (chelated Gd³⁺ and iron nanoparticles), male rat of Wistar strain, three patients with brain metastases.

FIELD STRENGTH/SEQUENCE: A 3-T and 7-T, saturation recovery (SR), and MPRAGE sequences.

ASSESSMENT: The MPRAGE T₁ measurement was compared to the reference SR method on phantoms and rat brain at 7-T. The robustness of the in vivo method was evaluated by studying the impact of misestimates of tissue proton density. Concentrations of Gd-based theranostic agents were measured at 3-T in gray matter and metastases in patients recruited in NanoRad clinical trial.

STATISTICAL TESTS: A linear model was used to characterize the relation between T₁ measurements from the MPRAGE and the SR acquisitions obtained in vitro at 7-T.

RESULTS: The slope of the linear model was 0.966 (R² = 0.9934). MPRAGE-based T₁ values measured in the rat brain were 1723 msec in the thalamus. MPRAGE-based T₁ values measured in patients in white matter and gray matter amounted to 747 msec and 1690 msec. Mean concentration values of Gd³⁺ in metastases were 61.47 μmol.

DATA CONCLUSION: The T₁ values obtained in vitro and in vivo support the validity of the proposed approach. The concentrations of Gd-based theranostic agents may be assessed in patients with metastases within a standard clinical imaging protocol using the MPRAGE sequence.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 1.

PMID:36315197 | DOI:10.1002/jmri.28509

Klin Lab Diagn. 2022 Oct 14;67(10):600-606. doi: 10.51620/0869-2084-2022-67-10-600-606.

ABSTRACT

The relationship between multiple sclerosis and the state of the human microbiome was studied, namely, the change in the representation of microbiota phylotypes, the proportion of coccal flora, the proportion of anaerobic, gram-negative, proteolytically active microflora, as well as the concentration of markers of bacterial plasmalogen and endotoxin in the blood. Microbiome studies were carried out by gas chromatography – mass spectrometry of microbial markers in the blood. A statistically significant increase in blood concentrations of the total level of microbial markers of bacterial plasmalogen and endotoxin was determined in multiple sclerosis, which may be associated with an increase in the permeability of the intestinal wall. In multiple sclerosis, the proportion of coccal, gram-negative, anaerobic microflora with a proteolytic type of metabolic activity increases. The correlations of the representation of microbiota phylotypes change due to the switching of the direct relationship Proteobacteria-Bacteroides to Proteobacteria-Firmicutes. In multiple sclerosis, Actinobacteria and Proteobacteria increase and Firmicutes decrease. Conclusion. The multiple sclerosis disease may be associated with pathological changes in the structure of the microbiome and the growth of endotoxemia, which may be one of the factors in the pathogenesis of the disease. New laboratory markers for diagnosing and predicting the course of MS have been proposed.

PMID:36315176 | DOI:10.51620/0869-2084-2022-67-10-600-606

Klin Lab Diagn. 2022 Oct 14;67(10):570-574. doi: 10.51620/0869-2084-2022-67-10-570-574.

ABSTRACT

Multiple myeloma (MM) is a malignant tumor occurring from plasma cells that produce an abnormal monoclonal immunoglobulin – a paraprotein. A distinctive feature of Bence-Jones myeloma is the excretion of monoclonal free light chains of immunoglobulins with 24h urine, and the absence of monoclonal intact immunoglobulins secretion. Comprehensive analysis of biochemical parameters in blood serum and 24h urine in patients with Bence-Jones multiple myeloma using electrophoretic and immunoturbidimetric methods to assess their sensitivity as biomarkers. 50 patients with a morphologically confirmed diagnosis of MM of the Bence-Jones immunochemical type were examined. 28 people without oncological diseases were examinedas a control. Detection of monoclonal secretion in blood serum and daily urine was performed by immunofixation electrophoresis on the Hydrasys 2 electrophoretic system (Sebia). The determination of free light chains of immunoglobulins (FLC) was performed by the immunoturbidimetric method (Binding Site) on an Advia 1800 analyzer (Siemens). Analysis of IgG, IgA, IgM, β2-microglobulin and C-reactive protein was performed on Cobas 6000 analyzer (Roche). The median excretion of Bence-Jones protein in 24h urine of MM patients was 0.49 g/24h (0.06-2.45 g/24h). In the blood serum, in 86% of cases, the presence of paraproteinemia, represented by κ and λ type light chains of immunogloublins was detected. At the same time, the frequency of detection of monoclonal secretion in blood serum in Bence-Jones type λ myeloma was 95.7%, which was statistically significantly higher than the frequency of detection of monoclonal secretion of type κ – 77.8%. In patients with identified paraproteinemia, Bence-Jones protein excretion in daily urine (median 0.82 g/day) was statistically significantly higher than in patients without a monoclonal component detected in blood serum (median 0.04 g/24h). The levels of FLC in blood serum obtained by immunoturbidimetry in Bence-Jones myeloma of the corresponding type were higher than the reference levels in 100% of cases. The median level of κ-FLC reached 4358 mg/l, λ-FLC – 2225 mg/l, which was statistically significantly higher than the control levels. The median concentrations of IgG, IgA and IgM in patients with Bence-Jones myeloma were statistically significantly lower than in the control group, while the medians of β2-microglobulin and C-reactive protein were significantly higher than in the control. Our investigation showed high diagnostic efficiency of electrophoretic and immunoturbidimetric analysis of monoclonal secretion in patients with Bence-Jones MM, while FLC analysis demonstrated maximum sensitivity. Bence-Jones MM revealed biochemical signs of secondary immunodeficiency and general inflammatory syndrome.

PMID:36315171 | DOI:10.51620/0869-2084-2022-67-10-570-574

Big Data. 2022 Oct 28. doi: 10.1089/big.2021.0064. Online ahead of print.

ABSTRACT

Artificial neural networks (ANNs) have been frequently used in forecasting problems in recent years. One of the most popular types of ANNs in these days is Pi-Sigma artificial neural networks (PS-ANNs). PS-ANNs have a high order ANN structure and they use both multiplicative and additive neuron models in their architecture. PS-ANNs produce superior forecasting performance because of their high order structure. PS-ANNs are affected negatively by an outlier or outliers in a data set because of having a multiplicative neuron model in their architecture. In this study, a new robust learning algorithm based on particle swarm optimization and Huber’s loss function for PS-ANNs is proposed. To evaluate the performance of the proposed method, Dow Jones stock exchange and Australian beer consumption data sets are analyzed and the obtained results are compared with many ANNs types proposed in the literature. Besides, the performance of the proposed method in outlier cases is also investigated by injecting outliers into these data sets. It is seen that the proposed learning algorithm has a satisfying performance both the data have an outlier or outliers’ case and original case.

PMID:36315168 | DOI:10.1089/big.2021.0064

Telemed J E Health. 2022 Oct 28. doi: 10.1089/tmj.2022.0193. Online ahead of print.

ABSTRACT

Background: Telehealth has seen breakthroughs in many fields of medicine, but utilization remains limited in orthopedic sports medicine. The purpose of this investigation was to compare patient satisfaction, duration of care, and overall patient experiences with telehealth and in-person clinical visits for sports-related injuries. Methods: A cross-sectional survey study was conducted at an orthopedic sports medicine clinic during the peak of the COVID-19 pandemic between March and November 2020. Anonymous electronic surveys were used to record patient responses and statistical comparisons were drawn through two-sample t-tests. Results: A total of 175 patients (82 telehealth vs. 93 in-person) consented to participate in this investigation, and all were included in the final analysis. The overall composite satisfaction score, when compared between the two groups, did not differ (p = 0.63). Duration of care was significantly longer in the 93 patients who had in-person clinical visits as compared with the 82 patients who had telehealth visits (61/93: >31 min vs. 75/82: <30 min; p < 0.001). Finally, of the 82 patients who had telehealth, 3 respondents said they were “very unlikely” and “unlikely” to request another virtual clinical visit and/or recommend this mode of health care delivery to friends or family. Of the 93 patients had in-person clinical visits, only 15 respondents stated they were uninterested in telehealth under any circumstance. Conclusion: Most patients presenting to an orthopedic sports medicine clinic are open to telehealth, recognize its utility, and believe it to be just as comparable with in-person clinical visits. Level of Evidence: IV.

PMID:36315167 | DOI:10.1089/tmj.2022.0193

J Cardiovasc Surg (Torino). 2022 Oct 31. doi: 10.23736/S0021-9509.22.12437-7. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiac surgery is performed worldwide to treat severe cases of cardiovascular diseases. Statins have shown controversial effects on complications after cardiac surgeries. We aimed to investigate the effect of preoperative statin therapy on the frequency of postoperative mortality, renal, and neurological complications.

METHODS: In a retrospective cohort study, the database of patients operated on in two hospitals in southern Iran during 2008-2019 was used to compare preoperative statin use with no use on the composite outcome of mortality, renal, and neurological complications as well as on each component of the composite, separately. Effects of low dose (<40 mg simvastatin equivalence) vs. high dose (≥40 mg) statins were also evaluated. Confounders that could affect the outcomes were considered in the logistic regression model, and multiple imputation techniques were used to categorize patients with unknown statin dose use as either high or lowdose users.

RESULTS: Of total 7329 patients, 17.6% of statin users and 17% of non-statin users developed the composite outcome (P=0.51). Statin use had no statistically significant association with the composite outcome (aRR 1.01 [95% CI: 0.88-1.16]). There was no significant association with mortality [aRR: 0.75 (95% CI: 0.34-1.69)], neurological [aRR: 1.25 (95% CI: 0.77-2.12)], or renal complications [aRR: 1.03 (95% CI 0.90-1.19)] after surgery. Neither low nor high doses had any statistically significant effect on the composite or any of its components.

CONCLUSIONS: In this large study, preoperative statin use, either high dose or low dose, did not affect short-term postoperative mortality, neurological, or renal complications.

PMID:36315166 | DOI:10.23736/S0021-9509.22.12437-7

JAMA Netw Open. 2022 Oct 3;5(10):e2237600. doi: 10.1001/jamanetworkopen.2022.37600.

ABSTRACT

IMPORTANCE: Preterm birth (PTB) is the leading cause of infant morbidity and mortality worldwide. It has been suggested that vaginal progesterone (VP) treatment may reduce the recurrence of PTB.

OBJECTIVE: To evaluate the association of VP treatment with prevention of recurrent PTB among patients with a singleton pregnancy.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, observational cohort study, set in a public health care system for inner-city pregnant patients, enrolled patients with prior spontaneous PTB (gestational age, ≤35 weeks) receiving VP from May 15, 2017, to May 7, 2019. Patients who delivered between 1998 and 2011 served as a referent cohort matched 3:1 for obesity, race and ethnicity, and individual specific preterm birth history. Statistical analysis was performed from August 19, 2021, to September 2, 2022.

EXPOSURE: Patients received 90 mg of vaginal progesterone, 8%, nightly, initiated between 16 weeks and 0 days and 20 weeks and 6 days of pregnancy until 36 weeks and 6 days of pregnancy or delivery.

MAIN OUTCOMES AND MEASURES: The primary outcome was overall rate of recurrent PTB at 35 weeks or less of patients given VP compared with the 3:1 matched untreated historical controls. Secondary outcomes included assessment of PTB according to adherence (≥80% completing scheduled doses), duration of pregnancy relative to index gestational age, progesterone blood levels, and outcomes for those who declined VP.

RESULTS: A total of 417 patients (mean [SD] age, 30.4 [5.9] years; 64 Black patients [15.3%]; 272 [65.2%] with a body mass index of ≥30) received VP and were matched with 1251 controls (mean [SD] age, 28.8 [5.7] years; 192 Black patients [15.3%]; 816 [65.2%] with a body mass index of ≥30). The overall rate of recurrent PTB was 24.0% (100 of 417; 95% CI, 20.0%-28.4%) for the VP cohort compared with 16.8% (1394 of 8278) expected in the matched historical controls. Adherence was not associated with lower rates of recurrent PTB compared with nonadherence (odds ratio, 0.87 [95% CI, 0.51-1.41]). The mean difference between historical matched controls and those using VP was 0.2 weeks (95% CI, -1.4 to 1.0 weeks) without improvement in the interval of recurrent PTB after the implementation of VP (P = .73). Progesterone blood levels for patients who were adherent compared with those who were nonadherent were not significantly different at either 24 or 32 weeks (24 weeks: 99 ng/mL [95% CI, 85-121 ng/mL] vs 104 ng/mL [95% CI, 89-125 ng/mL]; P = .16; 32 weeks: 200 ng/mL [95% CI, 171-242 ng/mL] vs 196 ng/mL [95% CI, 155-271 ng/mL]; P = .69).

CONCLUSIONS AND RELEVANCE: This cohort study of patients with a current singleton pregnancy suggests that VP was not associated with a reduction in recurrent PTB.

PMID:36315147 | DOI:10.1001/jamanetworkopen.2022.37600

JAMA Netw Open. 2022 Oct 3;5(10):e2239616. doi: 10.1001/jamanetworkopen.2022.39616.

ABSTRACT

IMPORTANCE: Prevalence of childhood parental death varies by race and ethnicity and socioeconomic status, yet whether similar variation persists in the association with lifetime psychiatric disorder is unknown.

OBJECTIVE: To assess whether race and ethnicity and parental educational attainment are associated with the risk of death of a parent; to determine whether the risk for lifetime psychiatric disorder associated with death of a parent was moderated by race and ethnicity and highest parental educational attainment; and to examine a potential intersection of race and ethnicity with parental educational attainment in the risk of lifetime psychiatric disorder associated with death of a parent.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from the National Comorbidity Study: Adolescent Supplement (NCS-A), 2001 to 2004. Participants included youth aged 13 to 18 years, restricted to Black, Hispanic, and White youth due to power limitations. Data were analyzed from February 26, 2021, to April 21, 2022.

EXPOSURE: Death of a parent during childhood.

MAIN OUTCOMES AND MEASURES: The primary study outcome was any lifetime Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) psychiatric disorder, assess via assessed via structured clinical interviews.

RESULTS: Among 9501 youth (mean [SD] age, 15.2 [1.5] years; 50.9% female), including 511 youth who had experienced parental death and 8990 youth who had not, the cumulative hazard of parental death by age 18 years was approximately doubled for Hispanic (10.1%; 95% CI, 6.9%-14.7%) and Black (14.0%; 95% CI, 10.6%-18.4%) youth compared with White youth (6.0%; 95% CI, 4.7%-7.8%). Similar patterns were noted by parental educational attainment: the cumulative hazard of parental death for youth of parents with less educational attainment was nearly double (10.1%; 95% CI, 8.1%-12.6%) compared with youth of parents with more education (6.6%; 95% CI, 5.2%-8.4%). Death of a parent was positively and significantly associated with risk of any lifetime psychiatric disorder (aOR, 1.34; 95% CI, 1.03-1.75) compared with youth who had not experienced death of a parent. However, this association was not moderated by race and ethnicity (aOR, 1.05; 95% CI, 0.58-1.92) or parental educational attainment (aOR, 1.19; 95%, 0.70-2.04), although power analyses suggest that larger sample sizes are needed.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, Black and Hispanic youth experienced elevated parental death compared with White youth, yet the risk for any lifetime psychiatric disorder after parental death was not significantly moderated by race and ethnicity or parental education. Both individual- and population-level interventions may be needed to address the increased risk of psychiatric disorders, although additional studies with larger sample sizes are needed.

PMID:36315141 | DOI:10.1001/jamanetworkopen.2022.39616

J Magn Reson Imaging. 2022 Oct 31. doi: 10.1002/jmri.28504. Online ahead of print.

ABSTRACT

BACKGROUND: Ferumoxytol, an intravenous iron supplement, is commonly used to treat anemia in pregnancy. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a viable off-label alternative to gadolinium-enhanced MRA for assessment of pulmonary embolism (PE) in pregnancy.

PURPOSE: To describe our clinical experience with Fe-MRA in pregnant women with suspected PE.

STUDY TYPE: Retrospective, observational, cohort.

POPULATION: A total of 98 Fe-MRA exams (consecutive sample) performed in 94 pregnant women.

FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T, 3D T1-weighted MRA.

ASSESSMENT: After IRB approval including a waiver of informed consent, electronic health records were reviewed retrospectively for all Fe-MRA exams performed at our institution in pregnant between January, 2017 and March, 2022. The Fe-MRA protocol included 3D-MRA for assessment of pulmonary arteries, and T1-weighted imaging for ancillary findings. Fe-MRA exam duration was measured from image time stamps. Fe-MRA exams were reviewed by three cardiovascular imagers using a 4-point Likert scale for image quality and confidence for PE diagnosis (score 4 = best, 1 = worst), and tabulation of ancillary findings.

STATISTICAL TESTS: Continuous data are presented as mean ± standard deviation. The overall image quality and confidence score is given as the mean of three readers.

RESULTS: The 98 Fe-MRA exams were performed in 94 pregnant women (age 30 ± 6, range 19-48 years, gestational week 23 ± 10, range 3-38 weeks), with four undergoing two Fe-MRA exams during their pregnancy. Median Fe-MRA exam durration was 8 minutes (interquantile range 6 minutes). Overall image quality score was 3.3 ± 0.9. Confidence score for diagnosing PE was 3.5 ± 0.8. One subject was positive for PE (1/94, 1%); 42 of the 94 (45%) subjects Fe-MRA had ancillary findings including hydronephrosis or pneumonia.

CONCLUSION: Ferumoxytol enhanced MRA is a radiation- and gadolinium-free alternative for diagnosis of PE during pregancy.

EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 5.

PMID:36315131 | DOI:10.1002/jmri.28504