Nevin Manimala

Bull Math Biol. 2021 May 26;83(7):80. doi: 10.1007/s11538-021-00912-5.

ABSTRACT

Mechanical and mechanochemical models of pattern formation in biological tissues have been used to study a variety of biomedical systems, particularly in developmental biology, and describe the physical interactions between cells and their local surroundings. These models in their original form consist of a balance equation for the cell density, a balance equation for the density of the extracellular matrix (ECM), and a force-balance equation describing the mechanical equilibrium of the cell-ECM system. Under the assumption that the cell-ECM system can be regarded as an isotropic linear viscoelastic material, the force-balance equation is often defined using the Kelvin-Voigt model of linear viscoelasticity to represent the stress-strain relation of the ECM. However, due to the multifaceted bio-physical nature of the ECM constituents, there are rheological aspects that cannot be effectively captured by this model and, therefore, depending on the pattern formation process and the type of biological tissue considered, other constitutive models of linear viscoelasticity may be better suited. In this paper, we systematically assess the pattern formation potential of different stress-strain constitutive equations for the ECM within a mechanical model of pattern formation in biological tissues. The results obtained through linear stability analysis and the dispersion relations derived therefrom support the idea that fluid-like constitutive models, such as the Maxwell model and the Jeffrey model, have a pattern formation potential much higher than solid-like models, such as the Kelvin-Voigt model and the standard linear solid model. This is confirmed by the results of numerical simulations, which demonstrate that, all else being equal, spatial patterns emerge in the case where the Maxwell model is used to represent the stress-strain relation of the ECM, while no patterns are observed when the Kelvin-Voigt model is employed. Our findings suggest that further empirical work is required to acquire detailed quantitative information on the mechanical properties of components of the ECM in different biological tissues in order to furnish mechanical and mechanochemical models of pattern formation with stress-strain constitutive equations for the ECM that provide a more faithful representation of the underlying tissue rheology.

PMID:34037880 | DOI:10.1007/s11538-021-00912-5

Eur J Orthop Surg Traumatol. 2021 May 26. doi: 10.1007/s00590-021-03010-3. Online ahead of print.

ABSTRACT

PURPOSE: Back pain may both decrease patient satisfaction after TKA and confound outcome assessment in satisfied patients. Our primary objective was to determine whether preoperative back pain is associated with differences in postoperative patient-reported outcome measures (PROMs).

METHODS: We retrospectively reviewed 234 primary TKA patients who completed PROMs preoperatively and 12 weeks postoperatively, which included a back pain questionnaire, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) and the Forgotten Joint Score-12 (FJS-12). Cohorts were defined based on the severity of preoperative back pain (none, mild, moderate and severe) and compared. Demographics were compared using ANOVA and Chi-square analysis. Univariate ANCOVA analysis was utilized to compare PROMs while accounting for significant demographic differences.

RESULTS: Both preoperative KOOS JR scores (none: 47.90, mild: 47.61, moderate: 44.61 and severe: 38.70; p = 0.013) and 12-week postoperative KOOS JR scores (none: 61.24, mild: 64.94, moderate: 57.48 and severe: 57.01; p = 0.012) had a statistically significant inverse relationship with regard to the intensity of preoperative back pain. Although FJS-12 scores at the 12-week postoperative period trended lower with increasing levels of preoperative back pain (p = 0.362), it did not reach statistical significance. Patients who reported severe back pain preoperatively achieved the largest delta improvement from baseline compared to those with lesser pain intensity (p = 0.003). Patients who had a 2-grade improvement in their back pain achieved significantly higher KOOS JR scores 12 weeks postoperatively compared to patients with either 1-grade or no improvement (63.53 vs. 55.98; p = 0.042). Both preoperative (47.99 vs. 41.11; p = 0.003) and 12-week postoperative (64.06 vs. 55.73; p < 0.001) KOOS JR scores were statistically higher for those who reported mild or no back pain pre-and postoperatively than those who reported moderate or severe back pain pre-and postoperatively.

CONCLUSION: Knee pain and back pain both exert negative effects on outcome instruments designed to measure pain and function. Although mean improvement from pre- to postoperative KOOS JR scores for patients with severe pre-existing back pain was higher than their counterparts, this statistical difference is likely not clinically significant. This implies that all patients may experience similar benefits from TKA despite the presence or absence of back pain. Attempts to measure TKA outcomes using PROMs should seek to control for lumbago and other sources of body pain. Level of Evidence IIIRetrospective Cohort Study.

PMID:34037858 | DOI:10.1007/s00590-021-03010-3

J Math Biol. 2021 May 26;82(7):64. doi: 10.1007/s00285-021-01613-2.

ABSTRACT

We analyze ecological systems that are influenced by random environmental fluctuations. We first provide general conditions which ensure that the species coexist and the system converges to a unique invariant probability measure (stationary distribution). Since it is usually impossible to characterize this invariant probability measure analytically, we develop a powerful method for numerically approximating invariant probability measures. This allows us to shed light upon how the various parameters of the ecosystem impact the stationary distribution. We analyze different types of environmental fluctuations. At first we study ecosystems modeled by stochastic differential equations. In the second setting we look at piecewise deterministic Markov processes. These are processes where one follows a system of differential equations for a random time, after which the environmental state changes, and one follows a different set of differential equations-this procedure then gets repeated indefinitely. Finally, we look at stochastic differential equations with switching, which take into account both the white noise fluctuations and the random environmental switches. As applications of our theoretical and numerical analysis, we look at competitive Lotka-Volterra, Beddington-DeAngelis predator-prey, and rock-paper-scissors dynamics. We highlight new biological insights by analyzing the stationary distributions of the ecosystems and by seeing how various types of environmental fluctuations influence the long term fate of populations.

PMID:34037835 | DOI:10.1007/s00285-021-01613-2

Eur Radiol. 2021 May 26. doi: 10.1007/s00330-021-07948-0. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the ability of CT radiomic features extracted from peritumoral parenchyma of 2 mm and 5 mm distinguishing invasive adenocarcinoma (IAC) from adenocarcinoma in situ (AIS)/minimally invasive adenocarcinoma (MIA).

METHODS: For this retrospective study, 121 lung adenocarcinomas appearing as ground-glass nodules on thin-section CT were evaluated. Quantitative radiomic features were extracted from the peritumoral parenchymal region of 2 mm and 5 mm on CT imaging, and the radiomic models of External2 and External5 were constructed. The ROC curves were used to evaluate the performance of different models. Differences between the AUCs were evaluated using DeLong’s method.

RESULTS: The radiomic scores of IAC were statistically higher than those of MIA/AIS in both the External2 and External5 models. The AUCs of the External2 and External5 models were 0.882, 0.778 in the training cohort and 0.888, 0.804 in the validation cohort, respectively. The AUC of the External2 model was not statistically different from the External5 model both in the training cohort (p = 0.116) and validation cohort (p = 0.423).

CONCLUSIONS: The radiomic features extracted from the peritumoral region of 2 mm and 5 mm at thin-section CT showed good predictive values to differentiate the IAC from AIS/MIA. The radiomic features from the peritumoral region of 5 mm provide no additional benefit in distinguishing IAC from MIA/AIS than that of the 2 mm region.

KEY POINTS: • The radiomic models from various peritumoral lung parenchyma were developed and validated to predict invasiveness of adenocarcinoma. • The peritumoral parenchyma of lung adenocarcinoma may contain useful information. • Radiomics from peritumoral lung parenchyma of 5 mm provides no added efficiency of the prediction for invasiveness of lung adenocarcinoma.

PMID:34037830 | DOI:10.1007/s00330-021-07948-0

J Trop Pediatr. 2021 May 17;67(2):fmab044. doi: 10.1093/tropej/fmab044.

ABSTRACT

BACKGROUND: Structural congenital heart defects (CHD) take a huge toll of congenital defects in children in India. Limited information is available regarding modifiable risk factors for its causation. This study was planned with an aim to determine the prevalence of congenital rubella infection in Indian infants with structural CHD’s.

METHODOLOGY: This cross-sectional, observational study was conducted at a tertiary care hospital in Northern India over 1 year period (1 July 2016 to 30 June 2017). Infants <6 months with structural CHD were enrolled after taking informed consent from their mothers. Blood samples were collected from mother-child binomials and tested for rubella IgM and IgG antibodies.

RESULTS: A total of 80 infants (M : F = 56 : 24), having mean age 69.4 (±56.5) days; were enrolled. In these infants, prevalence of congenital rubella infection (either infant’s IgM rubella positive or infant’s IgG rubella titers higher than mother’s) was 8.75% (7/80). A total of 12.5% of studied mothers were seronegative for rubella IgG antibodies. Statistically significant association was found between the occurrence of congenital rubella and cataract (p = 0.0039), splenomegaly (p = 0.007) and microcephaly (p = 0.0084) in infants having structural CHD.

CONCLUSIONS: Congenital rubella syndrome still remains an important modifiable cause for structural CHD in India. Sincere efforts for rubella elimination via further strengthening current vaccination strategy would help in decreasing burden of structural CHD in India.

PMID:34037788 | DOI:10.1093/tropej/fmab044

Transl Behav Med. 2021 May 26:ibab028. doi: 10.1093/tbm/ibab028. Online ahead of print.

ABSTRACT

Physical activity (PA) and exercise are safe and beneficial for children and adolescents affected by cancer. Yet, this population is not active enough to receive benefits. PA guideline and recommendation statements can support individual behavior and practice change. The purpose of this project was to develop the international Pediatric Oncology Exercise Guidelines (iPOEG), comprised of guideline and recommendation statements, to promote PA among children and adolescents affected by cancer. Guideline development procedures, stakeholder engagement strategies, and the Delphi technique were used. Four online surveys were distributed to the iPOEG network (n = 9 core team members, n = 122 expert consensus committee members). Surveys included closed- and open-ended items informed by a literature synthesis and an in-person meeting. Responses were analyzed using descriptive statistics and content analysis. Consensus was defined as ≥ 80% agreement. Response rates to online surveys ranged from 82% to 91%. The iPOEG network agreed on four guideline and five recommendation statements, which highlight that movement is important for all children and adolescents affected by cancer. These statements are generic in nature as more research is still required to provide specific guidance on the frequency, intensity, time, and type of PA for this population. Nevertheless, the iPOEG statements represent available evidence and expert opinion, collectively suggesting that it is time for children and adolescents affected by cancer to move more.

PMID:34037786 | DOI:10.1093/tbm/ibab028

Interact Cardiovasc Thorac Surg. 2021 May 25:ivab103. doi: 10.1093/icvts/ivab103. Online ahead of print.

ABSTRACT

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, ‘in patients undergoing coronary artery bypass grafting is semi-skeletonized harvesting superior to pedicled harvesting of the left internal mammary artery (LIMA) in terms of conduit length, flow, rate of sternal wound infections and post-operative bleeding?’. Altogether, 235 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. Three studies were cohort studies and 2 were randomized controlled trials. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. One randomized controlled trial showed superiority with semi-skeletonized harvesting in terms of conduit length (P < 0.001), flow (P = 0.004) and diastolic filling (P = 0.005). Three studies included data on surgical wound infections/mediastinitis, all of which reported n = 0. One randomized controlled trial and 3 cohort studies reported that semi-skeletonized harvesting reduced postoperative bleeding. No studies reported a statistically significant difference in operative time. This review suggests that semi-skeletonized harvesting could possibly be associated with favourable outcomes when compared to pedicled harvesting with respect to graft length and flow, and lower postoperative bleeding, without increasing operative time; although there is insufficient data to compare sternal wound infections or long-term outcomes. In conclusion, the limited evidence base prevents robust informed decision-making when comparing both techniques.

PMID:34037772 | DOI:10.1093/icvts/ivab103

JAMA Netw Open. 2021 May 3;4(5):e2111582. doi: 10.1001/jamanetworkopen.2021.11582.

ABSTRACT

IMPORTANCE: Arthroscopic meniscectomy is one of the most common orthopedic procedures. The optimal postoperative approach remains debated.

OBJECTIVE: To compare outcomes associated with home-based rehabilitation programs (HBP) vs standard inpatient and/or outpatient supervised physical therapy (IOP) following arthroscopic isolated meniscectomy (AM).

DATA SOURCES: A systematic literature search was conducted on PubMed, Web of Science, Cochrane Library, and Scopus databases on March 15, 2021. The included studies were published from 1982 to 2019.

STUDY SELECTION: Randomized clinical trials of patients treated with HBP vs IOP after AM were included.

DATA EXTRACTION AND SYNTHESIS: Data were independently screened and extracted by 2 authors according to the Preferred Reporting Items for Systematic Reviews (PRISMA) reporting guideline. The meta-analysis was performed using a random-effect model; when an I2 < 25% was observed, the fixed-effect model was used. The Hartung-Knapp correction was applied.

MAIN OUTCOMES AND MEASURES: The primary outcome was the Lysholm score (scale of 0-100 with higher scores indicating better knee function) and secondary outcomes were subjective International Knee Documentation Committee (IKDC) score, knee extension and flexion, thigh girth, horizontal and vertical hop test, and days to return to work, as indicated in the PROSPERO registration. Outcomes were measured in the short-term (ranging from 28 to 50 days) and the midterm (6 months).

RESULTS: In this meta-analysis of 8 RCTs including 434 patients, IOP was associated with a greater short-term improvement in Lysholm score compared with HBP, with a mean difference of -8.64 points (95% CI, -15.14 to -2.13 points; P = .02) between the 2 approached, but the sensitivity analysis showed no difference. Similarly, no statistically significant difference was detected at midterm for Lysholm score, with a mean difference between groups of -4.78 points (95% CI, -9.98 to 0.42 points; P = .07). HBP was associated with a greater short-term improvement in thigh girth, with a mean difference between groups of 1.38 cm (95% CI, 0.27 to 2.48 cm; P = .01), whereas IOP was associated with a better short-term vertical hop score, with a mean difference between groups of -3.25 cm (95% CI, -6.20 to -0.29 cm; P = .03). No differences were found for all the other secondary outcomes.

CONCLUSIONS AND RELEVANCE: No intervention was found to be superior in terms of physical and functional outcomes as well as work-related and patient-reported outcomes, both at short-term and midterm follow-up. Overall, these results suggest that HBP may be an effective management approach after AM in the general population.

PMID:34037730 | DOI:10.1001/jamanetworkopen.2021.11582

Am J Hypertens. 2021 May 26:hpab083. doi: 10.1093/ajh/hpab083. Online ahead of print.

ABSTRACT

BACKGROUND: Aim of our study was to compare adherence to antihypertensive drug therapy between newly treated patients in whom monotherapy or a two-drug single-pill combination (SPC) was initially dispensed.

METHODS: The 63,448 residents of Lombardy Region (Italy), aged 40-80 years, who were newly treated with antihypertensive drugs during 2016, were identified and followed for 1 year after the first prescription. The outcome of interest was adherence to drug therapy that was measured according to the “proportion of days covered” (PDC) criterion, i.e. the ratio between the number of days in which the drug was available and the days of follow-up. Patients who had a PDC>75% and <25% were defined as highly and poorly adherent to drug therapy, respectively. Log-binomial regression models were fitted to compare the propensity to treatment adherence between the initial therapeutic strategies, after adjusting for baseline demographic and clinical covariates.

RESULTS: About 46% and 17% of patients showed high and poor adherence, respectively. Compared to patients under initial monotherapy (85%), those who were initially treated with a SPC (15%) had higher propensity to be highly adherent and a lower propensity to be poorly adherent to antihypertensive treatment (Risk Ratio: 1.18, 95% confidence interval 1.16-1.21; 0.42, 0.39-0.45, respectively). This was the case regardless the sex, the age, the patient clinical status, and with almost any type of SPC.

CONCLUSIONS: In a real-life setting, patients who were initially prescribed a two-drug SPC exhibited more frequently a good adherence to antihypertensive treatment than those starting with a single drug.

PMID:34037713 | DOI:10.1093/ajh/hpab083

JAMA Dermatol. 2021 May 26. doi: 10.1001/jamadermatol.2021.1677. Online ahead of print.

ABSTRACT

IMPORTANCE: Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by occlusion of hair follicles as a primary pathogenic factor. There are scarce data regarding the prevalence of HS.

OBJECTIVE: To estimate overall HS prevalence.

DATA SOURCES: This review and meta-regression analysis was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The academic search included PubMed, Cochrane registry, ClinicalTrials.gov, and evidence by NHS UK and Trip databases from inception through May 2020. To analyze HS prevalence, only cross-sectional studies or baseline assessments of longitudinal cohorts using census-based surveys or probabilistic and nonprobabilistic epidemiologic methods were considered. The search terms were (prevalence OR incidence OR epidemiology) AND (hidradenitis suppurativa OR acne inversa OR Verneuil’s disease). No language restriction was applied.

STUDY SELECTION: Original investigations that reported HS prevalence were included. After exclusion criteria were applied, 17 studies qualified for qualitative analysis, but only 16 studies were quantitatively assessed.

DATA EXTRACTION AND MEASURES: Two reviewers extracted data by age, diagnostic criteria, presence of any comorbidity, sample sizes, continent/location, sex, and other characteristics. Assessment of bias risk used the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence.

MAIN OUTCOMES AND MEASURES: Hidradenitis suppurativa prevalence (with 95% CI) among the overall population and among subgroups. Between-study heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).

RESULTS: In 16 quantitatively assessed studies included, prevalence estimates were reported only from Western European and Scandinavian countries, the US, and Australia. Meta-analysis with random effects, after adjusting for publication bias in the prevalence estimates, revealed a 0.40% prevalence (95% CI, 0.26%-0.63%) for HS. Studies based on clinical samples revealed a higher pooled prevalence of HS (1.7%) than population-based studies (0.3%).

CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-regression analysis may help facilitate policy formulation, channeling funding and guiding principles for better disease diagnosis using universal valid tools and management.

PMID:34037678 | DOI:10.1001/jamadermatol.2021.1677