Changes in neuroinflammatory biomarkers correlate with disease severity and neuroimaging alterations in patients with COVID-19 neurological complications.

COVID-19 induces acute and persistent neurological symptoms in mild and severe cases. Proposed concomitant mechanisms include direct viral infection and strain, coagulopathy, hypoxia, and neuroinflammation. However, underlying molecular alterations associated with multiple neurological outcomes in both mild and severe cases are majorly unexplored. To illuminate possible mechanisms leading to COVID-19 neurological disease, we retrospectively investigated in detail a cohort of 35 COVID-19 mild and severe hospitalized patients presenting neurological alterations subject to clinically indicated cerebrospinal fluid (CSF) sampling. Clinical and neurological investigation, brain imaging, viral sequencing, and cerebrospinal CSF analyses were carried out. We found that COVID-19 patients presented heterogeneous neurological symptoms dissociated from lung burden. Nasal swab viral sequencing revealed a dominant strain at the time of the study, and we could not detect traces of SARS-CoV-2's spike protein in patients' CSF by multiple reaction monitoring analysis. Patients presented ubiquitous systemic hyper-inflammation and broad alterations in CSF proteomics related to inflammation, innate immunity, and hemostasis, irrespective of COVID-19 severity or neuroimaging alterations. Elevated CSF interleukin-6 (IL6) correlated with disease severity (sex-, age-, and comorbidity-adjusted mean Severe 24.5 pg/ml, 95% confidence interval (CI) 9.62-62.23 vs. Mild 3.91 pg/mL CI 1.5-10.3 patients, p = 0.019). CSF tumor necrosis factor-alpha (TNFα) and IL6 levels were higher in patients presenting pronounced neuroimaging alterations compared to those who did not (sex-, age-, and comorbidity-adjusted mean TNFα Pronounced 3.4, CI 2.4-4.4 vs. Non-Pronounced 2.0, CI 1.4-2.5, p = 0.022; IL6 Pronounced 33.11, CI 8.89-123.31 vs Non-Pronounced 6.22, CI 2.9-13.34, p = 0.046). Collectively, our findings put neuroinflammation as a possible driver of COVID-19 acute neurological disease in mild and severe cases.

Synthesis and cytotoxic evaluation of heterocyclic compounds by vinylic substitution of ketene dithioacetals.

N-heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N-heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity. In silico predictions indicate that the two most active derivatives exhibit physicochemical properties within the range of drug-like compounds and showed potential to interact with HDAC8 and ERK1 cancer-related targets.

Low Plasma Lipids Are Associated with Relapsing and Lethal Visceral Leishmaniasis in HIV-Infected Patients.

Visceral leishmaniasis (VL) results from protozoa Leishmania infantum and L. donovani infection. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both groups of patients in the first episode and with relapsing VL. Still, the strongest blood cell indicator associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and twenty-three with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low low-density lipoprotein. After CD4+ decreases, lymphocyte CD8+ reduction is the final stage of immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia and fat exhaustion provoked by the co-occurrence of both diseases, which can finally lead to death.

Long-term Comparative Evaluation of Weight Loss and Complications of Banded and Non-banded Roux-en-Y Gastric Bypass.

PURPOSE: The use of a nonadjustable silicone band around the gastric pouch of Roux-en-Y gastric bypass (RYGB) to reduce the recurrence of obesity is still being debated in the literature. The primary objective of this study was to evaluate banded and non-banded RYGB regarding % total weight loss (%TWL) and complications up to 10 years postoperatively and regarding the removal rate of the silicone band. MATERIAL AND METHODS: A retrospective study of the medical records of all patients submitted to banded and non-banded RYGB between 2000 and 2020 was conducted. Clinical data (age, gender, weight, body mass index-BMI, comorbidities, %TWL, and the prevalence of vomiting) and laboratory data (hemoglobin, serum iron, albumin, and vitamin B12) were obtained preoperatively and at 6 months, 1, 2, 3, 5, 7, and 10 years for both groups and at 12, 15, and 20 years after banded RYGB. RESULTS: In total, 858 patients underwent RYGB: 409 underwent banded RYGB and 449 underwent non-banded RYGB. In the preoperative period, banded RYGB patients were heavier and had higher rates of hypertension and dyslipidemia. The %TWL was higher in the banded RYGB group up to 7 years. The prevalence of vomiting is much higher in this group, which also had lower laboratory test values. Of the banded RYGB patients, 9.53% had to have the silicone ring removed after presenting complications. CONCLUSION: Banded RYGB promotes significantly higher rates of TWL at the expense of a higher frequency of food intolerance and vomiting.

Characterization of the gut bacterial and viral microbiota in latent autoimmune diabetes in adults.

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by autoantibodies against insulin producing pancreatic beta cells and initial lack of need for insulin treatment. The aim of the present study was to investigate if individuals with LADA have an altered gut microbiota relative to non-diabetic control subjects, individuals with type 1 diabetes (T1D), and individuals with type 2 diabetes (T2D). Bacterial community profiling was performed with primers targeting the variable region 4 of the 16S rRNA gene and sequenced. Amplicon sequence variants (ASVs) were generated with DADA2 and annotated to the SILVA database. The gut virome was sequenced, using a viral particle enrichment and metagenomics approach, assembled, and quantified to describe the composition of the viral community. Comparison of the bacterial alpha- and beta-diversity measures revealed that the gut bacteriome of individuals with LADA resembled that of individuals with T2D. Yet, specific genera were found to differ in abundance in individuals with LADA compared with T1D and T2D, indicating that LADA has unique taxonomical features. The virome composition reflected the stability of the most dominant order Caudovirales and the families Siphoviridae, Podoviridae, and Inoviridae, and the dominant family Microviridae. Further studies are needed to confirm these findings.

Photosynthesis and other factors affecting the establishment and maintenance of cnidarian-dinoflagellate symbiosis.

Coral growth depends on the partnership between the animal hosts and their intracellular, photosynthetic dinoflagellate symbionts. In this study, we used the sea anemone Aiptasia, a laboratory model for coral biology, to investigate the poorly understood mechanisms that mediate symbiosis establishment and maintenance. We found that initial colonization of both adult polyps and larvae by a compatible algal strain was more effective when the algae were able to photosynthesize and that the long-term maintenance of the symbiosis also depended on photosynthesis. In the dark, algal cells were taken up into host gastrodermal cells and not rapidly expelled, but they seemed unable to reproduce and thus were gradually lost. When we used confocal microscopy to examine the interaction of larvae with two algal strains that cannot establish stable symbioses with Aiptasia, it appeared that both pre- and post-phagocytosis mechanisms were involved. With one strain, algae entered the gastric cavity but appeared to be completely excluded from the gastrodermal cells. With the other strain, small numbers of algae entered the gastrodermal cells but appeared unable to proliferate there and were slowly lost upon further incubation. We also asked if the exclusion of either incompatible strain could result simply from their cells' being too large for the host cells to accommodate. However, the size distributions of the compatible and incompatible strains overlapped extensively. Moreover, examination of macerates confirmed earlier reports that individual gastrodermal cells could expand to accommodate multiple algal cells. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.

The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS.

BACKGROUND: Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. METHODS: From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients' complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. RESULTS: CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = -0.71, P = 0.015). CONCLUSIONS: This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages.

Systematic Review of Post-Traumatic Parkinsonism, an Emerging Parkinsonian Disorder Among Survivors of Traumatic Brain Injury.

This systematic review focuses on an increasing subset of traumatic brain injury (TBI) survivors who develop post-traumatic parkinsonism (PTP), characterized by slowness of movement (bradykinesia), rigidity (stiffness), postural instability, and resting tremors caused by obstruction or damage to deep brain structures of the basal ganglia. PTP is rare, and one hypothesis to explain PTP rarity is that TBIs severe enough to affect deep brain structures are often lethal; however, with increasing survivability of TBIs, these numbers are expected to increase. The goal of this review is to raise awareness of an expected global increase of a subgroup of TBI patients who are treatment responsive and report therapeutic results aiding providers in diagnosing, educating, and treating PTP patients. Literature over the past 100 years was considered, and 44,663 peer-reviewed articles were identified. Inclusion criteria required a clinical indication of parkinsonian signs and TBI. Twenty-six case reports were ultimately included from which 36 individual patient data points were extracted for this review. Between 1980 and 2010, there has been an increase in reporting of PTP decade after decade. Forty-seven percent of PTP cases have 1-6 months of latency to symptom onset, and 83% of cases were male. PTP can occur with or without presence of brain lesions, and the most common type of injuries that cause PTP are motor vehicle accidents followed by falls. PTP patients are responsive to surgery or medication treatments. Further detail on PTP symptomology, treatment responsiveness, and injury types is provided.

Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans.

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders. We generated gestational epigenetic age estimates (DNAmGA) based on Knight and Bohlin epigenetic clocks. We also investigated the association between DNAmGA and UCB serum brain-derived neurotrophic factor (BDNF) levels. Considering the large-scale DNAm data availability and existing evidence regarding PCE as a risk for health problems later in life, we generated ES for tobacco smoking, psychosis, autism, diabetes, and obesity. A gene ontology (GO) analysis on the CpGs included in the ES with group differences was performed. PCE was associated with lower DNAmGA in newborns, and this effect remained significant when controlling for potential confounders, such as blood cell type composition predicted by DNAm and obstetric data. DNAmGA was negatively correlated with BDNF levels in the serum of UCB. Higher tobacco smoking, psychosis, and diabetes ES were found in the PCE group. The GO analysis revealed GABAergic synapses as a potential pathway altered by PCE. Our findings of decelerated DNAmGA and ES for adverse phenotypes associated with PCE, suggest that the effects of gestational cocaine exposure on the epigenetic landscape of human newborns are detectable at birth.

Reperfusion therapy for acute ischemic stroke: where are we in 2023? / Terapia de reperfusão para o acidente vascular isquêmico agudo: onde estamos em 2023?

Abstract Over the last three decades, stroke care has undergone significant transformations mainly driven by the introduction of reperfusion therapy and the organization of systems of care. Patients receiving treatment through a well-structured stroke service have a much higher chance of favorable outcomes, thereby decreasing both disability and mortality. In this article, we reviewed the scientific evidence for stroke reperfusion therapy, including thrombolysis and thrombectomy, and its implementation in the public health system in Brazil.

Resumo Nas últimas três décadas, o tratamento do AVC sofreu transformações significativas, impulsionadas principalmente pela introdução das terapias de reperfusão e pela organização dos serviços de AVC. Os pacientes que recebem tratamento em um serviço de AVC bem estruturado têm uma probabilidade muito maior de resultados favoráveis, diminuindo assim a incapacidade funcional e a mortalidade. Neste artigo, revisamos as evidências científicas para as terapias de reperfusão do AVC, incluindo trombólise e trombectomia e sua implementação no sistema público de saúde no Brasil.

Cochlear radiation dose and hearing loss in patients with vestibular schwannoma undergoing radiosurgery: systematic review

Abstract Objectives: To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery. Methods: A systematic review of the literature was performed without language or publication year restrictions in the MEDLINE/PubMed, EMBASE, Web of Science, LILACS/VHL and Cochrane Library databases. Studies that met the following criteria were included: 1) population: adults of both sexes who underwent radiosurgery for vestibular schwannoma treatment; 2) exposure: cochlear radiation; 3) outcome: hearing loss; 4) type of study: cohort. Two independent reviewers conducted the entire review process. The registration number in PROSPERO was CRD42020206128. Results: From the 333 articles identified in the searches, seven were included after applying the eligibility criteria. There was no standardization as to how to measure exposure or outcome in the included studies, and most studies did not present sufficient data to enable meta-analysis. Conclusion: It was not possible to determine a cut-off point for high cochlear dose that could be considered a risk factor for hearing loss.

Mitochondrial health index correlates with plasma circulating cell-free mitochondrial DNA in bipolar disorder.

Although mitochondrial dysfunction is known to play an essential role in the pathophysiology of bipolar disorder (BD), there is a glaring gap in our understanding of how mitochondrial dysfunction can modulate clinical phenotypes. An emerging paradigm suggests mitochondria play an important non-energetic role in adaptation to stress, impacting cellular resilience and acting as a source of systemic allostatic load. Known as mitochondrial allostatic load, this (phenomenon) occurs when mitochondria are unable to recalibrate and maintain cell homeostasis. This study aimed to evaluate the composite mitochondrial health index (MHI) in BD subjects and non-psychiatry controls. We will also explore whether lower MIH will be related to higher cell-free mtDNA (ccf-mtDNA) levels and poor clinical outcomes. In this study, 14 BD-I patients and 16 age- and sex-matched non-psychiatry controls were enrolled. Peripheral blood mononuclear cells (PBMCs) were used to measure the enzymatic activities of citrate synthase and complexes I, II, and IV and mtDNA copy number. Ccf-mtDNA was evaluated by qPCR in plasma. Mitochondrial quality control (MQC) proteins were evaluated by western blotting. After adjusting for confounding variables, such as age, sex, body mass index (BMI), and smoking status, patients with BD presented lower MHI compared to non-psychiatry controls, as well as higher ccf-mtDNA levels that negatively correlated with MHI. Because the MQC network is essential to maintain mitochondrial health, MHI and ccf-mtDNA were also examined in relation to several MQC-related proteins, such as Fis-1, Opa-1, and LC3. Our results showed that MHI correlated negatively with Fis-1 and positively with Opa-1 and LC3. Accordingly, ccf-mtDNA had a positive correlation with Fis-1 and a negative correlation with Opa-1 and LC3. Furthermore, we found a noteworthy inverse correlation between illness severity and MHI, with lower MHI and higher ccf-mtDNA levels in subjects with a longer illness duration, worse functional status, and higher depressive symptoms. Our findings indicate that mitochondrial allostatic load contributes to BD, suggesting mitochondria represent a potential biological intersection point that could contribute to impaired cellular resilience and increased vulnerability to stress and mood episodes. Ultimately, by linking mitochondrial dysfunction to disease progression and poor outcomes, we might be able to build a predictive marker that explains how mitochondrial function and its regulation contribute to BD development and that may eventually serve as a treatment guide for both old and new therapeutic targets.

Cochlear radiation dose and hearing loss in patients with vestibular schwannoma undergoing radiosurgery: systematic review.

OBJECTIVES: To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery. METHODS: A systematic review of the literature was performed without language or publication year restrictions in the MEDLINE/PubMed, EMBASE, Web of Science, LILACS/VHL and Cochrane Library databases. Studies that met the following criteria were included: 1) population: adults of both sexes who underwent radiosurgery for vestibular schwannoma treatment; 2) exposure: cochlear radiation; 3) outcome: hearing loss; 4) type of study: cohort. Two independent reviewers conducted the entire review process. The registration number in PROSPERO was CRD42020206128. RESULTS: From the 333 articles identified in the searches, seven were included after applying the eligibility criteria. There was no standardization as to how to measure exposure or outcome in the included studies, and most studies did not present sufficient data to enable meta-analysis. CONCLUSION: It was not possible to determine a cut-off point for high cochlear dose that could be considered a risk factor for hearing loss.

Gender-Related Health Care Discrimination and Human Papillomavirus Vaccination Among Transgender and Nonbinary Young Adults in the United States.

Although transgender and nonbinary (TNB) people can acquire human papillomavirus (HPV), research examining HPV vaccination in these populations is scarce. TNB individuals experience high levels of gender-related health care discrimination, which may undermine HPV vaccine uptake. Using data from a national online survey (N=716), we found a negative association between gender-related health care discrimination and HPV vaccination among transgender women and nonbinary individuals who were assigned male at birth (AMAB; odds ratio [OR]=0.52; 95% confidence interval [CI]: 0.29-0.93). Addressing gender-related health care discrimination may facilitate HPV vaccination and help prevent HPV-related cancers among transgender women and nonbinary AMAB individuals.

Single-Response Electronic Tongue and Machine Learning Enable the Multidetermination of Extracellular Vesicle Biomarkers for Cancer Diagnostics Without Recognition Elements.

Platforms based on impedimetric electronic tongue (nonselective sensor) and machine learning are promising to bring disease screening biosensors into mainstream use toward straightforward, fast, and accurate analyses at the point-of-care, thus contributing to rationalize and decentralize laboratory tests with social and economic impacts being achieved. By combining a low-cost and scalable electronic tongue with machine learning, in this chapter, we describe the simultaneous determination of two extracellular vesicle (EV) biomarkers, i.e., the concentrations of EV and carried proteins, in mice blood with Ehrlich tumor from a single impedance spectrum without using biorecognizing elements. This tumor shows primary features of mammary tumor cells. Pencil HB core electrodes are integrated into polydimethylsiloxane (PDMS) microfluidic chip. The platform shows the highest throughput in comparison with the methods addressed in the literature to determine EV biomarkers.

Unsaturated or saturated dietary fat-mediated steatosis impairs hepatic regeneration following partial hepatectomy in mice.

BACKGROUND: Partial hepatectomy is a preferred treatment option for many patients with hepatocellular carcinoma however, pre-existing pathological abnormalities originating from hepatic steatosis can alter the decision to perform surgery or postoperative outcomes as a consequence of the impact steatosis has on liver regeneration. AIM: The aim of this study was to investigate the role of a saturated or unsaturated high fat diet-mediated steatosis on liver regeneration following partial hepatectomy. METHODS: Mice were fed a low-fat control diet (CD, 13% fat), lard-based unsaturated (LD, 60% fat) or milk-based saturated high fat diet (MD, 60% fat) for 16 weeks at which time partial hepatectomy (approx. 70% resection) was performed. At days-2 and 7 post hepatectomy, one hour prior to euthanization, mice were injected with 5-bromo-2'-deoxyuridine in order to monitor hepatic regeneration. Serum was collected and assessed for levels of ALT and AST. Resected and regenerated liver tissue were examined for inflammation-indicative markers employing RT-PCR, Western blots, and histological methods. RESULTS: Mice fed LD or MD exhibited higher NAFLD scores, increased expression of inflammatory cytokines, neutrophil infiltration, macrophage accumulation, increased apoptosis, and elevated levels of serum ALT and AST activities, a decrease in the number of BrdU-incorporated-hepatocytes in the regenerated livers compared to the mice fed CD. Mice fed MD showed significantly lower percent of BrdU-incorporated hepatocytes and a higher trend of inflammation compared to the mice fed LD. CONCLUSION: A diet rich in saturated or unsaturated fat results in NASH with decreased hepatic regeneration however unsaturated fat diet cause lower inflammation and higher regeneration than the saturated fat diet following partial hepatectomy in mice.

Red Meat Intake, Indole-3-Acetate, and Dorea longicatena Together Affect Insulin Resistance after Gastric Bypass.

Roux-en-Y Gastric bypass (RYGB) promotes improvement in type 2 diabetes (T2D) shortly after surgery, with metabolic mechanisms yet to be elucidated. This study aimed to investigate the relationship between food intake, tryptophan metabolism, and gut microbiota on the glycemic control of obese T2D women after RYGB surgery. Twenty T2D women who underwent RYGB were evaluated before and three months after surgery. Food intake data were obtained by a seven-day food record and a food frequency questionnaire. Tryptophan metabolites were determined by untargeted metabolomic analysis, and the gut microbiota was determined by 16S rRNA sequencing. The glycemic outcomes were fasting blood glucose, HbA1C, HOMA-IR, and HOMA-beta. Linear regression models were applied to assess the associations between the changes in food intake, tryptophan metabolism, and gut microbiota on glycemic control after RYGB. All variables changed after RYGB (p < 0.05), except for tryptophan intake. Jointly, the variation in red meat intake, plasma indole-3-acetate, and Dorea longicatena was associated with postoperative HOMA-IR {R2 0.80, R2 adj 0.74; p < 0.01}. Red meat intake decreased three months after bariatric surgery while indole-3-acetate and Dorea longicatena increased in the same period. These combined variables were associated with better insulin resistance in T2D women after RYGB.

Association between the epigenetic lifespan predictor GrimAge and history of suicide attempt in bipolar disorder.

Bipolar disorder (BD) has been previously associated with premature mortality and aging, including acceleration of epigenetic aging. Suicide attempts (SA) are greatly elevated in BD and are associated with decreased lifespan, biological aging, and poorer clinical outcomes. We investigated the relationship between GrimAge, an epigenetic clock trained on time-to-death and associated with mortality and lifespan, and SA in two independent cohorts of BD individuals (discovery cohort - controls (n = 50), BD individuals with (n = 77, BD/SA) and without (n = 67, BD/non-SA) lifetime history of SA; replication cohort - BD/SA (n = 48) and BD/non-SA (n = 47)). An acceleration index for the GrimAge clock (GrimAgeAccel) was computed from blood DNA methylation (DNAm) and compared between groups with multiple general linear models. Differences in epigenetic aging from the discovery cohort were validated in the independent replication cohort. In the discovery cohort, controls, BD/non-SA, and BD/SA significantly differed on GrimAgeAccel (F = 5.424, p = 0.005), with the highest GrimAgeAccel in BD/SA (p = 0.004, BD/SA vs. controls). Within the BD individuals, BD/non-SA and BD/SA differed on GrimAgeAccel in both cohorts (p = 0.008) after covariate adjustment. Finally, DNAm-based surrogates revealed possible involvement of plasminogen activator inhibitor 1, leptin, and smoking pack-years in driving accelerated epigenetic aging. These findings pair with existing evidence that not only BD, but also SA, may be associated with an accelerated biological aging and provide putative biological mechanisms for morbidity and premature mortality in this population.

Limb alignment changes with knee flexion: A study based on CAS data.

BACKGROUND: Recent evidence has questioned the value of standing limb alignment for predicting the adduction moment and forces exerted on healthy and prosthetic knees. The purpose of this study was to assess the lower limb alignment of OA knee patients at various knee flexion angles. The main hypothesis was that lower limb alignment measured throughout knee flexion does not significantly differ between patients displaying different extension alignment (neutral, varus or valgus). METHODS: 206 arthritic knee patients undergoing computer-assisted total (CAS) knee prosthesis were included. Frontal limb alignment was assessed in a systematic manner by CAS at three knee positions: extension, 90 degrees of flexion and maximal flexion. The HKA angle at each knee position and the change in HKA angle between two knee positions (delta value) were reported and compared. RESULTS: A large proportion of OA patients had significant variation in their lower limb alignment (32% with Δ HKA > 5°). The extended limb deformity tended to reduce with knee flexion: mean of 5° and 6° deformity reduction for varus and valgus patients, 40% and 66% of varus and valgus patients progressed to neutral alignment with 90° knee flexion. Forty percent of neutral extended lower limb did not maintain their neutral alignment but rather progressed to either varus or valgus at 90° knee flexion. CONCLUSIONS: Limb alignment in extension is a poor predictor of limb alignment in flexion in OA patients. Only considering the traditional frontal alignment of an extended lower limb for planning knee arthroplasty or osteotomy is likely insufficient.

Influence of Pre-Milling of Cr3C2-25 NiCr Spray Powder on the Fatigue Life of HVOF-Sprayed Coating on ASTM A516 Steel Substrate.

The aim of the present investigation is to evaluate the influence of the powder size of Cr3C2-25NiCr spraying powder on the fatigue behavior of HVOF-sprayed coating on the ASTM A516 steel substrate. Conventional commercial Cr3C2-25NiCr spraying powder was previously treated through high-energy milling. The crystallite sizes of milled powders were measured by X-ray diffraction and transmission electronic microscopy. Three different powder formats of the same Cr3C2-25NiCr composite were subjected to HVOF spraying to produce (i) a Milled-Coating (from high-energy milled spray powder), (ii) an Original-Coating (from conventional commercial spray powder), and (iii) a 50%-50% mixture of both (Milled + Original-Coating). The same spraying conditions were adopted for all the assessed cases. The sprayed coatings were investigated through the Knoop hardness test and SEM-EDS analysis. In addition, 3-point bending fatigue tests were conducted at different stress levels up to 107 cycles. The coating morphology and roughness effects on fatigue behavior were analyzed. The Cr3C2-25NiCr milled coating presented a lower fatigue life above the fatigue limit and a higher fatigue limit than other coatings; this outcome could be attributed to its lower surface roughness and finer grain size microstructure.