Nevin Manimala

J Am Podiatr Med Assoc. 2022 Apr 27;112(2):20-244. doi: 10.7547/20-244.

ABSTRACT

BACKGROUND: Plantar fasciitis is a common cause of musculoskeletal discomfort. Minimally invasive interventions are preferred as second-line treatments following failure of conservative management. We report on a novel technique of ultrasound-guided percutaneous release of the medial third of the plantar fascia with the use of a fine cutting device for the treatment of persistent plantar fasciitis.

METHODS: This is a retrospective case series of all patients treated with the technique between 2013 and 2015. Patients had failed conservative management for a minimum of 6 months. The procedure was performed in an outpatient setting under local anesthesia. Under continuous ultrasound guidance, release of the medial third of the plantar fascia from the calcaneus was performed using an ophthalmic V-Lance knife through a medial stab wound entry point.

RESULTS: Fifteen patients (six men and nine women) with an average age of 54.7 years were included. The mean (standard deviation [SD]) visual analogue scale score for pain improved significantly, from 66.0 (SD, 18.8) preoperatively to each consecutive follow-up point: 29.3 (SD, 25.2) at 2 weeks, 30.0 (SD, 27.8) at 4 weeks, and 34.0 (SD, 26.1) at 12 weeks (P < .001). The mild increase in visual analogue scale score between 4 and 12 weeks was statistically significant (P = .018). Average duration of required analgesia was 5.5 days and average time required to return to usual activities was 5.7 days. Two patients suffered with refractory neuropathic pain over the lateral border of the foot without any obvious abnormality.

CONCLUSIONS: Ultrasound-guided percutaneous release with the use of a fine cutting device could be an alternative option for the treatment of persistent plantar fasciitis. The technique is not without complications, and a mild but statistically significant decline in pain levels from early to short term has been detected. Therefore, the long-term outcomes of this technique need to be investigated before we can advocate its routine use.

PMID:36115031 | DOI:10.7547/20-244

NMR Biomed. 2022 Sep 17:e4832. doi: 10.1002/nbm.4832. Online ahead of print.

ABSTRACT

INTRODUCTION: Monitoring renal allograft function after transplantation is key for early detection of allograft impairment, which in turn could contribute to preventing the loss of the allograft. Multiparametric renal MRI (mpMRI) is a promising non-invasive technique to assess and characterize renal physiopathology, however, few studies have employed mpMRI in renal allografts with stable function (maintained function over a long time period).

PURPOSE: To evaluate reproducibility of mpMRI in transplanted patients and to characterize normal values of the measured parameters. To estimate labeling efficiency of PCASL in the infrarenal aorta, using numerical simulations considering experimental measurements of aortic blood flow profiles.

METHODS: Subjects: Twenty transplanted patients with stable kidney function, maintained over one year. MRI protocol: Pseudo-Continuous Arterial Spin Labeling (PCASL), Intravoxel Incoherent Motion (IVIM) and T1 inversion recovery. Phase-contrast to measure aortic blood flow.

DATA ANALYSIS: renal blood flow (RBF), diffusion coefficient D, pseudo-diffusion coefficient D*, flowing fraction f and T1 maps were calculated and mean values were measured in the cortex and medulla. PCASL labeling efficiency was estimated from Bloch equations simulation.

STATISTICAL ANALYSIS: Reproducibility was assessed with the within-subject coefficient of variation, intra class correlation coefficient and Bland-Alman analysis. Correlations were evaluated using Pearson correlation coefficient. Significance level: P < 0.05.

RESULTS: Cortical reproducibility was very good for T1, D, RBF, moderate for f and low for D*, while medullary reproducibility was good for T1 and D. Significant correlations in the cortex between RBF and f (r=0.66), RBF and eGFR (r=0.64) and D* and eGFR (r=-0.57) were found.

CONCLUSION: Normal values of the measured parameters employing mpMRI protocol in transplanted kidney patients with stable function were characterized and the results showed good reproducibility of the techniques.

PMID:36115029 | DOI:10.1002/nbm.4832

Angew Chem Int Ed Engl. 2022 Sep 17. doi: 10.1002/anie.202205726. Online ahead of print.

ABSTRACT

α-Synuclein (α-syn) is an intrinsically disordered protein (IDP) that undergoes liquid-liquid phase separation (LLPS), fibrillation, and forms insoluble intracellular Lewy’s bodies in neurons, which are the hallmark of Parkinson’s Disease (PD). Neurotoxicity precedes the formation of aggregates and might be related to α-syn LLPS. The molecular mechanisms underlying the early stages of LLPS are still elusive. To obtain structural insights into α-syn upon LLPS, we take advantage of cross-linking/mass spectrometry (XL-MS) and introduce an innovative approach, termed COMPASS (COMPetitive PAiring StatisticS). In this work, we show that the conformational ensemble of α-syn shifts from a ‘hairpin-like’ structure towards more ‘elongated’ conformational states upon LLPS. We obtain insights into the critical initial stages of LLPS and establish a novel mass spectrometry-based approach that will aid to solve open questions in LLPS structural biology.

PMID:36115020 | DOI:10.1002/anie.202205726

Endocrine. 2022 Sep 17. doi: 10.1007/s12020-022-03184-8. Online ahead of print.

ABSTRACT

OBJECTIVES: The sensitivities of the pituitary to thyroxine feedback, and the thyroid to thyrotropin stimulation determine the free thyroxine /thyrotropin feedback loop and can be described mathematically by two curves. It is not well understood how the two curves combine in a healthy population with normal thyroid function to express the individual balance points that are observed. This study was directed at this issue testing the possibilities of random combination and directed linkage between the two curves.

METHODS: We reverse-engineered two sets of population data, on the assumption of independent combinations of thyroid and pituitary sensitivities, to obtain estimates of the curve describing thyroid sensitivity. Sensitivity studies were performed.

RESULTS: No analysis resulted in a physiologically feasible estimate of the curve describing thyroid sensitivity. There was evidence of linkage of the two curves in terms of their combination throughout the normal range. Thyroid response curves reflecting a low free thyroxine response to thyrotropin tended to be combined in individuals with thyrotropin curves reflecting a high thyrotropin response to free thyroxine, and vice versa.

CONCLUSIONS: Thyroid and pituitary sensitivities are linked, being combined in individuals in a non-random directed pattern. Direct mutual interaction may contribute to this linkage. This linkage precludes the derivation of the curves describing these sensitivities from population data of the free thyroxine and thyrotropin relationship and complicates their derivation by physiological experimentation. This linkage and probable interaction may also bestow evolutionary advantage by minimising inter-individual variation in free thyroxine levels and by augmenting homeostasis.

PMID:36115005 | DOI:10.1007/s12020-022-03184-8

Qual Life Res. 2022 Sep 17. doi: 10.1007/s11136-022-03252-6. Online ahead of print.

ABSTRACT

PURPOSE: A joint modeling approach is recommended for analysis of longitudinal health-related quality of life (HRQoL) data in the presence of potentially informative dropouts. However, the linear mixed model modeling the longitudinal HRQoL outcome in a joint model often assumes a linear trajectory over time, an oversimplification that can lead to incorrect results. Our aim was to demonstrate that a more flexible model gives more reliable and complete results without complicating their interpretation.

METHODS: Five dimensions of HRQoL in patients with esophageal cancer from the randomized clinical trial PRODIGE 5/ACCORD 17 were analyzed. Joint models assuming linear or spline-based HRQoL trajectories were applied and compared in terms of interpretation of results, graphical representation, and goodness of fit.

RESULTS: Spline-based models allowed arm-by-time interaction effects to be highlighted and led to a more precise and consistent representation of the HRQoL over time; this was supported by the martingale residuals and the Akaike information criterion.

CONCLUSION: Linear relationships between continuous outcomes (such as HRQoL scores) and time are usually the default choice. However, the functional form turns out to be important by affecting both the validity of the model and the statistical significance.

TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, number NCT00861094.

PMID:36115002 | DOI:10.1007/s11136-022-03252-6

Int J Clin Pharm. 2022 Sep 17. doi: 10.1007/s11096-022-01447-y. Online ahead of print.

ABSTRACT

BACKGROUND: Of all hospital admissions in older patients, 10-30% seem to be medication-related. However, medication-related admissions are often unidentified in clinical practice. To increase the identification of medication-related hospital admissions in older patients a triggerlist is published in the Dutch guideline for polypharmacy.

AIM: To assess whether the triggerlist has value as selection criterion to identify patients at high risk of medication-related hospital admissions.

METHOD: This retrospective cohort study was carried out in 100 older (≥ 60 years) patients with polypharmacy and having two triggers from the triggerlist. The admissions were assessed as either possibly or unlikely medication-related according to the Assessment Tool for identifying Hospital Admissions Related to Medications.

RESULTS: Of all the admissions 48% were classified as possibly medication-related. Patients with a possible medication-related hospital admission were more likely to have an impaired renal function (p = 0.015), but no differences with regard to age, sex, comorbidity or number of medicines were found.

CONCLUSION: The high prevalence of medication-related hospital admissions, suggests the triggerlist may have added value as selection criterion in a cohort of older patients with polypharmacy and can be used to improve the identification of a population at high risk of medication-related hospital admissions.

PMID:36115001 | DOI:10.1007/s11096-022-01447-y

Neurol Sci. 2022 Sep 17. doi: 10.1007/s10072-022-06386-0. Online ahead of print.

ABSTRACT

BACKGROUND: Age-related declines in cognitive function may begin in midlife.

PURPOSE: To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment.

METHODS: Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors.

RESULTS: Participants (N = 2421) were a mean age of 49 years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1_{Tertile(T)3 vs T1-2} hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RR_T3 vs _T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 10³/μL) were associated with 5-year cognitive decline.

CONCLUSIONS: Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious.

PMID:36114981 | DOI:10.1007/s10072-022-06386-0

Matern Child Health J. 2022 Sep 17. doi: 10.1007/s10995-022-03492-5. Online ahead of print.

ABSTRACT

BACKGROUND: The relationship between housing instability and reproductive healthcare is understudied. We examined the association between housing insecurity and access and utilization of general healthcare, contraceptive healthcare, and abortion care.

METHODS: Using data from a population-representative survey of adult reproductive-age Ohio women (N = 2,529), we assessed housing insecurity (not paying rent/mortgage on time in the past year). We examined associations between housing insecurity and the following outcomes: (1) not being able to access general healthcare in the past year; (2) experiencing delays or difficulties in accessing contraceptive healthcare in the past year; and (3) ever having an abortion. We used unadjusted and adjusted logistic regression models. We selected confounders a priori and included age, socioeconomic status, and healthcare status.

RESULTS: Overall, 10.6% of Ohio women of adult reproductive age experienced housing insecurity. Approximately 27.5% of respondents were not able to access general healthcare and 10.4% experienced delays or difficulties in accessing contraceptive care. Compared to housing-secure respondents, housing-insecure women were less able to access general healthcare (adjusted odds ratio [aOR]:2.16; 95% confidence interval [CI]:1.45-3.23) and more likely to experience delays or difficulties when accessing contraceptive care (aOR:1.74; 95% CI:1.00-3.04). Insecure housing was not statistically associated with ever having an abortion (aOR:1.76; 95% CI:0.93-3.34).

CONCLUSIONS: In this study, recent housing insecurity was associated with poorer access to general and contraceptive healthcare. Studies utilizing multidimensional measures of housing insecurity and other material insecurity measures are needed to further explore the relationship between material insecurity and access to general and contraceptive care.

PMID:36114977 | DOI:10.1007/s10995-022-03492-5

Breast Cancer Res Treat. 2022 Sep 17. doi: 10.1007/s10549-022-06744-8. Online ahead of print.

ABSTRACT

PURPOSE: The impact of elevated body mass index (BMI) on overall survival (OS) in patients receiving modern anthracycline-taxane chemotherapy for early breast cancer (EBC) has not yet been well established. The purpose of our study was to examine overall survival (OS) by BMI category in women with EBC receiving either doxorubicin (A), cyclophosphamide (C) + paclitaxel (P) or fluorouracil (F), epirubicin (E), cyclophosphamide (C) + docetaxel (D).

METHODS: This was a retrospective cohort study in patients ≥ 18 years with resected stage I-III BC diagnosed between 2007 and 2017 in Ontario, identified through linkage of administrative databases. Patients were classified according to baseline BMI into underweight (< 18.5 kg/m²), normal (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), and obese (≥ 30 kg/m²) World Health Organization (WHO) categories. The primary outcome was OS. Univariable and multivariable analyses were used to examine the association between clinico-pathologic characteristics and OS among BMI categories.

RESULTS: Our cohort included 11,601 women, of whom 3890 (33.5%) were normal weight, 3696 (31.9%) overweight, and 3847 (33.1%) obese. Median OS was 7.9 years. There were no statistically significant differences in OS according to BMI (p = 0.66) in the overall study cohort or among the BMI categories after adjusting for age, nodal status, stage, grade, ER and HER2 status for either AC-P or FEC-D- treated patients (p = 0.45 and p = 0.97, respectively).

CONCLUSIONS: Our large population-based retrospective cohort analysis of EBC patients receiving adjuvant anthracycline-taxane chemotherapy found no significant impact of BMI on OS. Further investigation is warranted to confirm these findings in prospective patient cohorts.

PMID:36114940 | DOI:10.1007/s10549-022-06744-8

Breast Cancer Res Treat. 2022 Sep 17. doi: 10.1007/s10549-022-06689-y. Online ahead of print.

ABSTRACT

PURPOSE: To present an overview of the management of male patients with Ductal Carcinoma In Situ of the breast (male DCIS).

METHODS: We retrospectively studied all male patients with a diagnosis of pure DCIS from January 1999 to December 2018: 20 patients were identified in our cancer referral center. We collected data regarding clinical presentation, age of onset, radiological features, receptor status of the neoplasm, histological type, and the follow-up of those patients.

RESULTS: The median age was 62 years (range 21-80). All patients underwent surgery, in 15/20 (75%) cases a mastectomy was carried out. Two patients (10%) underwent endocrine treatment and 1/20 (5%) underwent radiotherapy. The receptor status for 15/20 patients was documented: 13/15 patients were ER+/Pr+. In 3 cases the Ki 67% was positive (i.e., > 20%). All cases were negative for Her2. The median follow-up time was 9.0 years (IQR 4.0-13.7). Only one patient had an ipsilateral recurrence with the finding of an infiltrating carcinoma in the same breast after 14 years. The 5-year disease-free survival was 92.9%.

CONCLUSION: Pure DCIS in men is an extremely rare disease: proper diagnosis and management allow an excellent prognosis.

PMID:36114939 | DOI:10.1007/s10549-022-06689-y