Biomechanical considerations for an easily-restricted robot-assisted kinematic alignment: a surgical technique note.

BACKGROUND: In total knee arthroplasty, the normal kinematics of the knee may not be restored solely based on preoperative gait, fluoroscopic-based, and dynamic radiostereometric analyses. SURGICAL TECHNIQUE CASE PRESENTATION: This note introduced a 69-year-old male patient who sustained post-traumatic osteoarthritis of his right knee. He underwent robot-assisted total knee arthroplasty based on anatomical reproduction of knee stability during the swing phase of gait. The kinematic alignment was simply achieved within an easy-to-identified range after preoperative radiographic assessment, intraoperative landmarking and pre-validated osteotomy, and intraoperative range of motion testing. CONCLUSIONS: This novel technique allows personalized and imageless total knee arthroplasty. It provides a preliminary path in reproducing the anatomy alignment, natural collateral ligament laxity, and accurate component placement within safe-to-identified alignment boundaries.

Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAB-ergic activity and cortical plasticity in long COVID-19 syndrome.

OBJECTIVE: Transcranial magnetic stimulation (TMS) studies showed that patients with cognitive dysfunction and fatigue after COVID-19 exhibit impaired cortical GABAB-ergic activity, as revealed by reduced long-interval intracortical inhibition (LICI). Aim of this study was to test the effects of co-ultramicronized palmitoylethanolamide/luteolin (PEA-LUT), an endocannabinoid-like mediator able to enhance GABA-ergic transmission and to reduce neuroinflammation, on LICI. METHODS: Thirty-nine patients (26 females, mean age 49.9 ± 11.4 years, mean time from infection 296.7 ± 112.3 days) suffering from persistent cognitive difficulties and fatigue after mild COVID-19 were randomly assigned to receive either PEA-LUT 700 mg + 70 mg or PLACEBO, administered orally bid for eight weeks. The day before (PRE) and at the end of the treatment (POST), they underwent TMS protocols to assess LICI. We further evaluate short-latency afferent inhibition (SAI) and long-term potentiation (LTP)-like cortical plasticity. RESULTS: Patients treated with PEA-LUT but not with PLACEBO showed a significant increase of LICI and LTP-like cortical plasticity. SAI remained unaffected. CONCLUSIONS: Eight weeks of treatment with PEA-LUT restore GABAB activity and cortical plasticity in long Covid patients. SIGNIFICANCE: This study confirms altered physiology of the motor cortex in long COVID-19 syndrome and indicates PEA-LUT as a candidate for the treatment of this post-viral condition.

Medially congruent total knee arthroplasty in valgus knee deformities yields satisfactory outcomes: a multicenter, international study.

PURPOSE: Postoperative instability represents one of the most common complications following primary total knee arthroplasty (TKA). To prevent this outcome, valgus deformities have been historically treated using more constrained implants. The purpose of this study was to evaluate the outcome of treating a moderate valgus deformity by combining a surgical technique used to release the postero-lateral soft tissue envelope with the use of a medially congruent (MC) TKA design without using classical, semi-constrained inserts. METHODS: Seventy-nine MC TKAs were performed by three surgeons at three institutions between 2016 and 2018 as part of a multicenter, international study. Inclusion criteria were: radiographic late-stage osteoarthritic knees with Ranawat's type 1 or 2 classification of valgus deformity and integrity of the medial capsular-ligament complex (less than 10 mm of medial opening during valgus stress test at 10° of knee flexion). Exclusion criteria were: BMI > 40; neuromuscular, metabolic, or immunologic disorders; or the inability to complete outcome measures or radiographic assessment. RESULTS: Seventy-seven patients (79 knees), 59 males and 18 females, were evaluated at 2-year minimum follow-up according to the Knee Society Score (KSS) and Forgotten Joint Score (FJS). Mean age at surgery was 70 years (range 48-91). The mean range of motion (ROM) improved from 110° (range 85°-130°) preoperatively to 121° (range 105°-135°) (p < 0.001) at the time of the last follow-up. Preoperative knee extension significantly improved from 3° (range - 15° to 20°) to 1° (range - 5° to 5°) of flexion at the last follow-up in all the patients. KSS and KSS Functional scores were 89 (range 65-100) and 82 points (range 55-100), respectively. The FJS obtained at the last follow-up was 72 (range 49-88). Two patients (2.5%) had major postoperative complications (one periprosthetic joint infection; one postoperative patellar fracture) requiring surgical interventions. CONCLUSIONS: In different surgeon's hands, the use of a modern medially congruent TKA design yielded good clinical outcomes at 2 years in a consecutive series of TKA in valgus arthritic knees. Postoperative instability was not recorded in this series and this finding was related to the high conformity design of the MC polyethylene insert, which significantly differs from classical posterior-stabilized (PS) designs. LEVEL OF EVIDENCE: IV.

Altered motor cortex physiology and dysexecutive syndrome in patients with fatigue and cognitive difficulties after mild COVID-19.

BACKGROUND AND PURPOSE: Fatigue and cognitive difficulties are reported as the most frequently persistent symptoms in patients after mild SARS-CoV-2 infection. An extensive neurophysiological and neuropsychological assessment of such patients was performed focusing on motor cortex physiology and executive cognitive functions. METHODS: Sixty-seven patients complaining of fatigue and/or cognitive difficulties after resolution of mild SARS-CoV-2 infection were enrolled together with 22 healthy controls (HCs). Persistent clinical symptoms were investigated by means of a 16-item questionnaire. Fatigue, exertion, cognitive difficulties, mood and 'well-being' were evaluated through self-administered tools. Utilizing transcranial magnetic stimulation of the primary motor cortex (M1) resting motor threshold, motor evoked potential amplitude, cortical silent period duration, short-interval intracortical inhibition, intracortical facilitation, long-interval intracortical inhibition and short-latency afferent inhibition were evaluated. Global cognition and executive functions were assessed with screening tests. Attention was measured with computerized tasks. RESULTS: Post COVID-19 patients reported a mean of 4.9 persistent symptoms, high levels of fatigue, exertion, cognitive difficulties, low levels of well-being and reduced mental well-being. Compared to HCs, patients presented higher resting motor thresholds, lower motor evoked potential amplitudes and longer cortical silent periods, concurring with reduced M1 excitability. Long-interval intracortical inhibition and short-latency afferent inhibition were also impaired, indicating altered GABAB -ergic and cholinergic neurotransmission. Short-interval intracortical inhibition and intracortical facilitation were not affected. Patients also showed poorer global cognition and executive functions compared to HCs and a clear impairment in sustained and executive attention. CONCLUSIONS: Patients with fatigue and cognitive difficulties following mild COVID-19 present altered excitability and neurotransmission within M1 and deficits in executive functions and attention.

Neuropsychological and neurophysiological correlates of fatigue in post-acute patients with neurological manifestations of COVID-19: Insights into a challenging symptom.

More than half of patients who recover from COVID-19 experience fatigue. We studied fatigue using neuropsychological and neurophysiological investigations in post-COVID-19 patients and healthy subjects. Neuropsychological assessment included: Fatigue Severity Scale (FSS), Fatigue Rating Scale, Beck Depression Inventory, Apathy Evaluation Scale, cognitive tests, and computerized tasks. Neurophysiological examination was assessed before (PRE) and 2 min after (POST) a 1-min fatiguing isometric pinching task and included: maximum compound muscle action potential (CMAP) amplitude in first dorsal interosseous muscle (FDI) following ulnar nerve stimulation, resting motor threshold, motor evoked potential (MEP) amplitude and silent period (SP) duration in right FDI following transcranial magnetic stimulation of the left motor cortex. Maximum pinch strength was measured. Perceived exertion was assessed with the Borg-Category-Ratio scale. Patients manifested fatigue, apathy, executive deficits, impaired cognitive control, and reduction in global cognition. Perceived exertion was higher in patients. CMAP and MEP were smaller in patients both PRE and POST. CMAP did not change in either group from PRE to POST, while MEP amplitudes declined in controls POST. SP duration did not differ between groups PRE, increased in controls but decreased in patients POST. Patients' change of SP duration from PRE to POST was negatively correlated to FSS. Abnormal SP shortening and lack of MEP depression concur with a reduction in post-exhaustion corticomotor inhibition, suggesting a possible GABAB-ergic dysfunction. This impairment might be related to the neuropsychological alterations. COVID-19-associated inflammation might lead to GABAergic impairment, possibly representing the basis of fatigue and explaining apathy and executive deficits.

Malariological baseline survey and in vitro antimalarial drug resistance in Gulu district, Northern Uganda.

A comprehensive, representative malaria survey has been carried out in a population of internally displaced persons (IDP) in the district of Gulu, Northern Uganda. It included 74 households and 390 persons, and covered socio-economic and environmental information, individual physical data, malaria and the drug sensitivity of Plasmodium falciparum. The prevalence of infections with Plasmodium falciparum was 54.4% at a geometric mean asexual parasitaemia of 229/microl blood, typical for hyperendemic conditions. P. falciparum turned out to be highly resistant to chloroquine and amodiaquine. It showed also reduced sensitivity against lumefantrine and artemisinin, obviously the result of the liberal use of the lumefantrine-artemether combination without evidence-based indication.

Clinical and parasitological response of Plasmodium falciparum to chloroquine and sulfadoxine/pyrimethamine in rural Uganda.

Following the WHO protocol for in-vivo tests in areas with intense transmission of uncomplicated falciparum malaria, a randomized comparison of the invivo efficacy of chloroquine alone, sulfadoxine/pyrimethamine alone, and their combined administration was carried out in the third quarter of 2001 in Kaberamaido District, northeastern Uganda. Malaria in the study area is hyper-endemic, with a high prevalence of Plasmodium falciparum. The patients were infants and young children with a median age of 15 months. Of the 117 originally enrolled patients, 104 had a complete follow-up with presentation at all scheduled examinations. In the chloroquine group (n = 42), 55% were classified as adequate clinical response, 26% as early treatment failure, and 19% as late clinical failure. In the sulfadoxine/pyrimethamine group (n = 30), the respective figures were 83%, 13% and 3%, and in the group with combined treatment (n = 32), 88%, 6% and 6%. In terms of clinical cure rate, speed of clinical relief and parasite clearance the combined treatment proved to be the most effective of the three drug regimens. In the patients with adequate clinical response, a significant post-therapeutic increase of the haematocrit was observed, which was particularly marked in patients who had also cleared their parasitaemia. Increase of the efficacy of chloroquine with age indicates the early development of semi-immunity in the study area, with conserved efficacy of chloroquine in semi-immune persons.