Category: Nevin Manimala

J Exp Orthop. 2022 Oct 22;9(1):107. doi: 10.1186/s40634-022-00543-2.

ABSTRACT

PURPOSE: The anterolateral ligament (ALL) has been defined as a key stabilizer of internal tibial rotation at 35° or more of knee flexion, with a minimal primary or secondary stabilizing role in the AP direction. This study aimed to demonstrate that anatomical reconstruction of the ALL confers rotational stability equal to that of the uninjured knee.

HYPOTHESIS: anteroposterior (AP) and rotatory laxity will significantly vary after ALL tenotomy and ALL reconstruction with the author’s previously described technique.

METHODS: After ultrasound (US) ALL identification, different kinematic measurements were performed with an image-less Computer-Assisted Navigation System with dedicated software for Laxity Analysis in 5 knee specimens. Anteroposterior (AP) translations and varus/valgus (VV) and Internal-External (IE) rotations were evaluated by two trained orthopedic surgeons before ALL section, after ALL section, and after ALL anatomical reconstruction with doubled ipsilateral autologous gracilis tendon.

RESULTS: ALL resection significantly increased laxity in IE rotations with knee 90° flexed (IE90) and AP translation with tibia internally rotated and the knee 30° flexed (APlat) (p < 0.05). ALL reconstruction significantly reduced laxity in IE90 and APlat (p < 0.05) and reduced VV rotations at 30° of flexion (VV30) (p < 0.05). There were no statistically significant elongation differences between native ALL and reconstructed ALL (graft) during laxity tests. The inter-operator repeatability of the tests was excellent for each measurement.

CONCLUSIONS: ALL acted as an important internal tibial rotation restrain at 90° and a significant (secondary) AP stabilizer at 30° of knee flexion. The presented ALL reconstruction technique significantly restored the increase of knee laxity produced by the ALL section.

SCIENTIFIC LEVEL: Case-Controlled Laboratory Study, Level III.

PMID:36271953 | DOI:10.1186/s40634-022-00543-2

Eur J Appl Physiol. 2022 Oct 22. doi: 10.1007/s00421-022-05072-5. Online ahead of print.

ABSTRACT

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations.

METHODS: Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO₃) or ACE inhibitor (ACE_i: enalapril) for 8 weeks and completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention.

RESULTS: Forty-eight participants (n_ACEi = 23, n_PLA = 25) completed the trial. Exercise training compliance was above 99%. After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased in m. vastus lateralis in both groups (all P < 0.05) without statistical differences between them (all time × treatment P > 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment P < 0.05) in PLA (51 [33;69] %) than in ACE_i (28 [13;43] %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m. deltoideus.

CONCLUSION: Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial oxidative capacity, glycolytic capacity and angiogenesis, with no overall effect of pharmacological ACE inhibition in healthy adults.

PMID:36271942 | DOI:10.1007/s00421-022-05072-5

Ann Hematol. 2022 Oct 22. doi: 10.1007/s00277-022-05003-6. Online ahead of print.

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) show suboptimal responses to the vaccines against SARS-CoV-2; it has been shown though that a booster dose of the BNT162b2 vaccine may lead to a significant increase in the seroconversion rates of immunocompromised patients. We conducted a prospective, non-interventional study to evaluate the immunogenicity of a third dose of the BNT162b2 vaccine in adult patients with CLL. Sera were tested before the first, after the second, and before and after the third dose for anti-SARS-CoV-2 receptor binding domain (RBD) spike protein IgG (anti-RBD). Thirty-nine patients with CLL were included in the study. The seroconversion rate increased from 28.2% before the third dose to 64.1% after the third dose and was higher in treatment-naïve patients (72.7% versus 47.1% in actively treated patients, p = 0.042). All but one patient achieving a seroconversion after the second dose retained after the third, while eight patients not achieving a seroconversion after the second dose (38.1%), did so after the third. Moreover, patients actively treated with venetoclax had a higher seroconversion rate than those treated with ibrutinib (87.5% versus 14.3%, p = 0.001). This study confirms the beneficial effect of a third dose of the BNT162b2 vaccine on the seroconversion rate in patients with CLL. Our results also strongly suggest that the use of venetoclax is correlated with higher immunogenicity/seroconversion rates than that of ibrutinib, a finding that has been reported by another study. A treatment strategy change during the pandemic favoring the use of venetoclax may be suggested based on our results, although these results should be validated in larger studies.

PMID:36271935 | DOI:10.1007/s00277-022-05003-6

Eur Arch Psychiatry Clin Neurosci. 2022 Oct 22. doi: 10.1007/s00406-022-01464-y. Online ahead of print.

ABSTRACT

Enhanced behavioral interventions are gaining increasing interest as innovative treatment strategies for major depressive disorder (MDD). In this study protocol, we propose to examine the synergistic effects of a self-administered home-treatment, encompassing transcranial direct current stimulation (tDCS) along with a video game based training of attentional control. The study is designed as a two-arm, double-blind, randomized and placebo-controlled multi-center trial (ClinicalTrials.gov: NCT04953208). At three study sites (Israel, Latvia, and Germany), 114 patients with a primary diagnosis of MDD undergo 6 weeks of intervention (30 × 30 min sessions). Patients assigned to the intervention group receive active tDCS (anode F3 and cathode F4; 2 mA intensity) and an action-like video game, while those assigned to the control group receive sham tDCS along with a control video game. An electrode-positioning algorithm is used to standardize tDCS electrode positioning. Participants perform their designated treatment at the clinical center (sessions 1-5) and continue treatment at home under remote supervision (sessions 6-30). The endpoints are feasibility (primary) and safety, treatment efficacy (secondary, i.e., change of Montgomery-Åsberg Depression Rating Scale (MADRS) scores at week six from baseline, clinical response and remission, measures of social, occupational, and psychological functioning, quality of life, and cognitive control (tertiary). Demonstrating the feasibility, safety, and efficacy of this novel combined intervention could expand the range of available treatments for MDD to neuromodulation enhanced interventions providing cost-effective, easily accessible, and low-risk treatment options.ClinicalTrials.gov: NCT04953208.

PMID:36271928 | DOI:10.1007/s00406-022-01464-y

Mil Med. 2022 Oct 22:usac320. doi: 10.1093/milmed/usac320. Online ahead of print.

ABSTRACT

INTRODUCTION: Transgender individuals have served openly in the U.S. Military since 2016. Official policies for transgender servicemembers continue to evolve, including approaches to physical fitness testing of transgender servicemembers. There is a paucity of scientific data regarding the effects of gender affirming hormone therapy (GAHT) on athletic performance for the past 24 months of treatment. Identification of expected trends in performance during and after gender transition is essential to allow for the development of appropriate military policy regarding when to assess servicemembers’ fitness by standards of their affirmed gender.

MATERIALS AND METHODS: We identified Department of the Air Force transgender patients using the Transgender Health Medical Evaluation Unit database and recorded dates of GAHT initiation through a retrospective chart review. We recorded performance values for the Air Force physical fitness test components 1 year before and up to 4 years after GAHT initiation. Performance measures were maximum sit-ups in 1 minute, push-ups in 1 minute, and 1.5-mile run time. Pre- and post-GAHT scores were compared using one-sample T-test to mean scores of Air Force-wide cisgender averages to assess for significant difference between affirmed transgender and cisgender airmen. We then performed the two one-sided test (TOST) procedure for equivalence with upper and lower bounds set at 1 SD from the means for cisgender airmen. Finally, using Z-scores, average transgender group scores were assigned a percentile rank with their respect to affirmed gender throughout the transition process.

RESULTS: Following initiation of GAHT, transgender males demonstrated statistically significant worse performance than cisgender males in all events until 3 years of GAHT. Their average scores would have attained a comfortable passing score within 1 year of GAHT. Transgender females’ performance showed statistically significantly better performance than cisgender females until 2 years of GAHT in run times and 4 years in sit-up scores and remained superior in push-ups at the study’s 4-year endpoint. TOST confirmed equivalence at all points where statistical difference was not demonstrated. Servicemembers approximate their pre-GAHT assigned gender percentile ranking in their affirmed gender in a manner consistent with hypothesis and TOST testing in the push-up event for both transgender males and females and in the 1.5-mile run event for transgender males.

CONCLUSIONS: In a sample of Air Force adult transgender patients, athletic performance measures demonstrate variable rates of change depending on the patients’ affirmed gender and differ by physical fitness test component. Based on this study, transgender females should begin to be assessed by the female standard no later than 2 years after starting GAHT, while transgender males could be assessed by their affirmed standard no earlier than 3 years after initiating GAHT.

PMID:36271916 | DOI:10.1093/milmed/usac320

Gynecol Endocrinol. 2022 Oct 22:1-6. doi: 10.1080/09513590.2022.2126453. Online ahead of print.

ABSTRACT

Background: The role of motile sperm count in intrauterine insemination (IUI) success rate is controversial. This retrospective cohort study performed among unselected infertile couples undergoing IUI was to explore the association between the total progressive motile sperm count (TPMSC) and the live birth rate (LBR) following IUI.Methods: The total cohort of 5363 cycles, 2666 infertile couples between January 2015 and December 2018 and finally 5171 cycles, 2647 couples were included for analysis in Sun Yat-sen memorial hospital of Sun Yat-sen University. The primary outcome was LBR per cycle. And the secondary outcome measure was clinical pregnancy rate (CPR) per cycle.Results: From the receiver operating characteristic (ROC) analysis of female age predicting live birth, female age cutoff was defined as 28 years. With a female age of ≤28 years, the CPRs were 11.5%, 14.9%, 16.1%, and 15.8% in quartile groups of pre-wash TPMSC, respectively. For the LBRs the values were 9.4%, 12.9%, 14.4%, and 11.3%, and there were also no significant differences in quartile groups of pre-wash TPMSC with ≤24 million (M), [24M-50M], [50M-97M], >97M. No statistically significant differences in the CPRs (p = .051) and LBRs (p = .088) were also observed in the quartiles groups of post-wash TPMSC. With a female age of >28 years, the CPR in couples with post-wash TPMSC ≤22.32 M was significantly lower than with post-wash TPMSC >81.0 M (p = .007). There was an obvious trend in which CPRs and LBRs increased with the post-wash TPMSC during the <81 M interval in women >28 years.Conclusions: The optimal female age cutoff for live birth was 28 years in IUI cycles. Pre-wash and post-wash TPMSC were not significantly associated with CPR and LBR per cycle. When female age >28 years, there was a better outcome with post-wash TPMSC >22.32 million.

PMID:36271782 | DOI:10.1080/09513590.2022.2126453

Clin Endocrinol (Oxf). 2022 Oct 22. doi: 10.1111/cen.14839. Online ahead of print.

ABSTRACT

CONTEXT: Aromatase inhibitor (AI) therapy provides oncological benefits in postmenopausal women with oestrogen-receptor positive breast cancer. However, AI treatment has been associated with increased cardiovascular risk. In non-breast cancer populations, experimentally-induced low oestrogen states and natural transition to menopause have been associated with increases in visceral adipose tissue (VAT), a known surrogate marker for cardiometabolic risk.

OBJECTIVE: Given that AI treatment blocks oestradiol production we hypothesised that AI treatment would increase VAT.

METHODS: We conducted a prospective 12-month cohort study of 52 postmenopausal women newly initiating AI treatment (median age 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (median age 63.5 years). VAT area and other body composition parameters were measured at baseline, 6- and 12-months using Dual X-ray Absorptiometry. Other risk markers of cardiometabolic health were also assessed.

RESULTS: In women initiating AI treatment, there was no statistically significant difference in VAT area after 12-months when compared to controls, mean adjusted difference -5.00 cm2 (-16.9, 6.91), p=0.55. Moreover, changes in total fat mass, lean mass, subcutaneous adipose tissue area, hepatic steatosis and measures in endothelial function were also not statistically different between groups after 12-months. Findings were similar after adjustments for activity levels and COVID-19 lockdown duration.

CONCLUSIONS: These data provide reassurance that over the initial 12-months of AI therapy, AI treatment is not associated with metabolically adverse changes in body composition, hepatic steatosis or vascular reactivity. The impact of extended AI therapy on cardiometabolic health requires further study. This article is protected by copyright. All rights reserved.

PMID:36271726 | DOI:10.1111/cen.14839

Pharmacotherapy. 2022 Oct 22. doi: 10.1002/phar.2738. Online ahead of print.

ABSTRACT

STUDY OBJECTIVE: The aim of this study was to evaluate the effect on bleeding risk when fluconazole is administered concomitantly with direct oral anticoagulants (DOACs).

DESIGN: This was a retrospective cohort study including hospitalized adult patients prescribed a DOAC with or without fluconazole.

SETTING: The Ohio State University Wexner Medical Center, a tertiary care academic medical center with more than 1800 beds.

PATIENTS: Hospitalized patients ages 18 to 89 years who received apixaban or rivaroxaban with or without fluconazole from October 1, 2016 to September 30, 2021 were included. The minimum duration of DOAC or DOAC with fluconazole therapy was 48 hours. Patients were excluded if they received fluconazole <400 mg daily or a DOAC at doses outside those recommended for atrial fibrillation or venous thromboembolism treatment or prophylaxis. Patients were matched based on DOAC received.

INTERVENTION: Patients who received a DOAC with fluconazole were compared to those receiving a DOAC alone. The primary outcome was a composite of major, clinically relevant nonmajor, and minor bleeding events at 30 days.

MEASUREMENTS AND MAIN RESULTS: There were 216 patients included, 108 in the DOAC with fluconazole group and 108 in the DOAC alone group. More patients in the DOAC with fluconazole group experienced bleeding at 30 days compared to the DOAC alone group [35/108 (32%) vs. 21/108 (19%), respectively; p=0.03]; however, after adjusting for proven confounding variables (hemoglobin and concomitant carvedilol) this was found not to be statistically significant [adjusted odds ratio 1.71, 95% confidence interval 0.85 to 3.40].

CONCLUSIONS: Patients receiving a DOAC with fluconazole were not at significantly increased risk for bleeding at 30 days compared to those receiving a DOAC alone after controlling for confounding variables. As an increasing number of patients are prescribed DOACs, the results of this study may inform clinical decision-making on the safety of concomitant DOAC and fluconazole use.

PMID:36271717 | DOI:10.1002/phar.2738

Eat Disord. 2022 Oct 22:1-16. doi: 10.1080/10640266.2022.2135738. Online ahead of print.

ABSTRACT

Treatment outcomes in eating disorders (EDs) are still an open field for clinicians and researchers. Besides difficulties in egosyntonic-linked treatment engagements, dropout is one of the most crucial elements that cause a reduction in the treatment efficacy. Thus, the aim of this study is to evaluate factors that could contribute to high dropout rates and non-participation in follow-up evaluation in patients with ED. This study used a large sample of patients from a specialized ED ward and day hospital (DH). A sample of 428 individuals was recruited for this study. Psychological and demographic data were collected at the time of hospitalization and discharge from the facilities. These data were used to explore a possible link between dropout and follow-up non-participation. Specially, the random forest was used to rank demographic and psychological features in importance and evaluate the top results with regression analyses for statistical significance. A dropout rate of 12.14% during inpatient and DH treatment was found. Anger-hostility and general psychopathology were found to be predictors of dropout during treatment, while the duration of the hospitalization predicted non-participation at the six-month follow-up. Specific psychological features should be considered before and during treatments for patients with EDs to reduce dropout rates. The duration of the hospitalization should also be evaluated as a relevant healthcare element that could affect engagement and, accordingly, outcome.

PMID:36271711 | DOI:10.1080/10640266.2022.2135738

Asia Pac J Clin Oncol. 2022 Oct 21. doi: 10.1111/ajco.13878. Online ahead of print.

ABSTRACT

AIM: To evaluate the change in signal intensity (SI) and volume (V) from multiparametric magnetic resonance imaging (MRI) for assessing the response of locally advanced rectal cancer (LARC) to chemoradiotherapy (CRT).

MATERIALS AND METHODS: Eight-two LARC patients who underwent pre- and post-CRT T2-weighted (T2W), apparent diffusion coefficient (ADC), and contrast-enhanced T1-weighted (ceT1W) MRI were retrospectively analyzed. The change of volume (%△V) and relative SI ratio (%△SIR) from each sequence were determined. All LARCs were confirmed pathologically and classified as tumor regression grade (TRG) -0, 1, 2,or 3. Descriptive statistics and receiver operating characteristic (ROC) analysis, with calculation of area under the curve (AUC), were used to compare the diagnostic performances.

RESULTS: Sixteen patients had TRG-0, 15 had TRG-1, 35 had TRG-2, and 16 had TRG-3. Except for ADC-%△SIR, the remaining %△V and %△SIR values on MR sequences had significant differences among the four groups. The %△V and %△SIR (alone or together) did not distinguish TRG-1 from TRG-2, nor TRG-2 from TRG-3; however, differences between other TRGs were identified by %△V and %△SIR. The combined use of ADC-%△V and T2W-%△SIR provided the best diagnostic performance in distinguishing of TRG-0 from TRG-2 (AUC: 0.954) and from TRG-3 (AUC: 1.000).

CONCLUSIONS: Preoperative MRI of LARC patients after CRT has high diagnostic value for determination TRG, and may therefore improve the selection of patients most suitable for surgery.

PMID:36271652 | DOI:10.1111/ajco.13878