Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ∼20% of the treated cases. Persistence of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious form decayed slowly with a half-life of ∼1 day, suggesting that its persistence could outlive the treatment course to re-ignite SARS-CoV-2 infection as the drug is eliminated. Notably, extending nirmatrelvir treatment beyond 8 days abolished viral rebound in vitro. Our findings point in a particular direction for future investigation of virus persistence and offer a specific treatment recommendation that should be tested clinically.

UNASSIGNED: We present a case of multiple tumefactive demyelinating lesions (TDLs) emerging 24 months after the second cycle of alemtuzumab treatment.
UNASSIGNED: A woman with relapsing-remitting multiple sclerosis (MS) discontinued fingolimod treatment due to gestational desire, which resulted in a severe disease exacerbation. Alemtuzumab was initiated, accompanied by regular clinical, radiological, and immunological monitoring.
UNASSIGNED: She relapsed prior to the second cycle, exhibiting 12 T1Gd+ lesions, and peripheral blood showed an increase in B-cells and a decrease in T-cells. At 24 months following the second cycle, she developed cognitive impairment and multiple T1Gd+ lesions, including TDLs, were evident on the brain MRI. We found not only an increase in B-cells but also in Th1 central memory cells. Th1/Th17 cells increased 3 months before the detection of TDLs.
UNASSIGNED: TDLs can appear 24 months after the second cycle of alemtuzumab treatment in MS. The increase in Th1/Th17 cells could be a candidate biomarker for TDLs in alemtuzumab-treated MS patients.

Predictors of rebound after correction of coronal plane deformities using temporary hemiepiphysiodesis (TH) are not well defined. The following research questions were tested: (1) Is the dynamic knee joint load useful to improve rebound prediction accuracy? (2) Does a large initial deformity play a critical role in rebound development? (3) Are BMI and a young age risk factors for rebound? Fifty children and adolescents with idiopathic knee valgus malalignment were included. A deviation of the mechanical femorotibial angle (MFA) of ≥ 3° into valgus between explantation and the one-year follow-up period was chosen to classify a rebound. A rebound was detected in 22 of the 50 patients (44%). Two predictors of rebound were identified: 1. reduced peak lateral knee joint contact force in the first half of the stance phase at the time of explantation (72.7% prediction); 2. minor initial deformity according to the MFA (70.5% prediction). The best prediction (75%) was obtained by including both parameters in the binary logistic regression method. A TH should not be advised in patients with a minor initial deformity of the leg axis. Dynamic knee joint loading using gait analysis and musculoskeletal modeling can be used to determine the optimum time to remove the plates.

Breathing and sleep state are tightly linked. The traditional approach to evaluation of breathing in rapid eye movement sleep has been to focus on apneas and hypopneas, and associated hypoxia or hypercapnia. However, rapid eye movement sleep breathing offers novel insights into sleep physiology and pathology, secondary to complex interactions of rapid eye movement state and cardiorespiratory biology. In this review, morphological analysis of clinical polysomnogram data to assess respiratory patterns and associations across a range of health and disease is presented. There are several relatively unique insights that may be evident by assessment of breathing during rapid eye movement sleep. These include the original discovery of rapid eye movement sleep and scoring of neonatal sleep, control of breathing in rapid eye movement sleep, rapid eye movement sleep homeostasis, sleep apnea endotyping and pharmacotherapy, rapid eye movement sleep stability, non-electroencephalogram sleep staging, influences on cataplexy, mimics of rapid eye movement behaviour disorder, a reflection of autonomic health, and insights into cardiac arrhythmogenesis. In summary, there is rich clinically actionable information beyond sleep apnea encoded in the respiratory patterns of rapid eye movement sleep.

UNASSIGNED: Nirmatrelvir/ritonavir (NM/r) is a safe and effective oral antiviral therapeutic used for treatment of mild-to-moderate COVID-19. Case reports described a clinical rebound syndrome whereby individuals experience a relapse of symptoms shortly after completing successful treatment. There is a lack of information on frequency of COVID-19 rebound after NM/r in routine clinical care, contributing factors, and clinical outcomes.
UNASSIGNED: We reviewed electronic medical records to verify COVID-19 diagnosis, symptoms, and treatment with NM/r from January-June 2022. We defined COVID-19 clinical rebound as clear improvement in symptoms followed by recurrence or worsening of symptoms within 30 days of a five-day course of NM/r.
UNASSIGNED: We studied 268 adults with median age 57 (IQR 47, 68), 80% White race, 85% non-Hispanic ethnicity, 55% female, 80% vaccinated and boosted against SARS-CoV-2, and 68% with any co-morbidity. Sixteen (6.0%) of studied patients were determined to have COVID-19 clinical rebound. The median time from starting NM/r to rebound was 11 days (IQR 9, 13). Notable demographic and clinical factors with higher proportion (not statistically significant) among COVID-19 rebound patients were female sex (75% rebound vs 54.5% no rebound), Black race (12.5% rebound vs 4.9% no rebound), presence of at least one co-morbidity (81.3% rebound vs 67.5% no rebound), and lack of prior SARS-CoV-2 infection (100% rebound vs 92.9% no rebound). Only one patient (6.25%) was hospitalized after COVID-19 rebound.
UNASSIGNED: COVID-19 clinical rebound after treatment with NM/r is mild with favorable outcomes and more common than previously reported from real-world clinical care studies.

BACKGROUND: Denosumab (Dmab) is widely used for the treatment of post-menopausal osteoporosis. Its discontinuation is sometimes accompanied by multiple vertebral fractures. Romosozumab (Rmab) has not been tested for its ability to prevent the rebound phenomenon.
METHODS: We present the case of a 68-year-old female patient with post-menopausal osteoporosis under treatment with Rmab who presented with multiple vertebral fractures after denosumab discontinuation. The addition of Rmab did not prevent new-onset rebound-associated vertebral fractures. The patient discontinued Rmab and Dmab was re-initiated. After six months, no new vertebral fractures occurred, bone mineral density increased and bone turnover markers remained suppressed.
CONCLUSIONS: Our clinical case illustrates the ineffectiveness of Rmab to prevent the multiple vertebral fracture cascade attributable to discontinuation of Dmab. We believe that treatment with Rmab might not be enough to prevent this phenomenon. Treatment with Dmab or possibly combination treatment with Dmab and Rmab could be another treatment option.

The development of urbanization and the resulting expansion of residential and transport infrastructures pose new challenges related to ensuring comfort for city dwellers. The emission of transport vibrations and household noise reduces the quality of life in the city. To counteract this unfavorable phenomenon, vibration isolation is widely used to reduce the propagation of vibrations and noise. A proper selection of vibration isolation is necessary to ensure comfort. This selection can be made based on a deep understanding of the material parameters of the vibration isolation used. This mainly includes dynamic stiffness and damping. This article presents a comparison of the method for testing dynamic stiffness and damping using a single degree of freedom (SDOF) system and the method using image processing, which involves tracking the movement of a free-falling steel ball onto a sample of the tested material. Rubber granules, rubber granules with rubber fibers, and rebound polyurethanes were selected for testing. Strong correlations were found between the relative indentation and dynamic stiffness (at 10-60 MN/m3) and the relative rebound and damping (for 6-12%). Additionally, a very strong relationship was determined between the density and fraction of the critical damping factor/dynamic stiffness. The relative indentation and relative rebound measurement methods can be used as an alternative method to measure the dynamic stiffness and critical damping factor, respectively.

OBJECTIVE: Metabolic and bariatric surgery (MBS) is the gold standard in treating severe obesity. Previous research implies that different psychological and behavior-related factors might be critical for MBS\' sustained success. Yet adherence to dietary behavior recommendations and its impact on weight development is rarely examined. This study investigated the relationship between adherence to dietary behavior recommendations and the percentage of total weight loss (%TWL) after MBS.
METHODS: This study is a cohort study (acquisition in Germany). N = 485 patients after MBS, being in grade III of obesity (body mass index (BMI) ≥ 40 kg/m2) pre-MBS, were included. Participants answered a standardized assessment on the relevant constructs, including adherence to dietary behavior recommendations, depression symptoms, weight, diet, and MBS characteristics.
RESULTS: BMI pre-MBS, type of MBS, age, regularity of physical activity, and depression symptoms were identified as significant covariates of %TWL and adherence. Within 6 months after MBS, adherence seems to peak, F(5,352) = 12.35, p < .001. Adherence and time since MBS predict %TWL. A higher adherence (moderator) is related to a higher %TWL, R2 = 52.65%, F(13,344) = 31.54, p < .001.
CONCLUSIONS: After MBS, adherence to dietary behavior recommendations seems crucial for maximizing its success. Implications for the optimization of MBS\' success in aftercare management arise. In particular, behavior modification interventions should be routinely implemented.

UNASSIGNED: Viral SARS-CoV-2 rebound (viral RNA rebound) is challenging to characterize in large cohorts due to the logistics of collecting frequent and regular diagnostic test results. Pharmacy-based testing data provide an opportunity to study the phenomenon in a large population, also enabling subgroup analyses. The current real-world evidence approach complements approaches focused on smaller, prospective study designs.
UNASSIGNED: We linked real-time reverse transcription quantitative polymerase chain reaction test data from national pharmacy-based testing to health care claims data via tokenization to calculate the cumulative incidence of viral RNA rebound within 28 days following positive test results in nirmatrelvir/ritonavir (NMV-r)-treated and untreated individuals during the Omicron era (December 2021-November 2022) and prior to the Omicron era (October 2020-November 2021).
UNASSIGNED: Among 30 646 patients, the rate of viral RNA rebound was 3.5% (95% CI, 2.0%-5.7%) in NMV-r-treated infections as compared with 1.5% (95% CI, 1.3%-1.7%) in untreated infections during the Omicron era and 1.9% (95% CI, 1.7%-2.1%) prior to the Omicron era. Viral RNA rebound in patients who were vaccinated (n = 8151), high risk (n = 4411), or older (≥65 years, n = 4411) occurred at comparable rates to the overall cohort (range, 1.1%-4.8%). Viral rebounds to high RNA levels in NMV-r-treated infections occurred in 8% of viral rebounds as compared with 5% to 11% in untreated infections. Rates of hospitalization were comparable between patients with NMV-r-treated infections with viral RNA rebound (0%) and untreated patients with viral RNA rebound (0%-1.2%).
UNASSIGNED: Our findings suggest viral RNA rebound is rare (< 5%), with rates that were consistent with those from the EPIC-HR trial (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients). Most occurrences of viral RNA rebound were associated with low viral RNA levels, and viral RNA rebound progression to severe disease was not observed.

In severe osteoporosis, the optimal approach for sequential treatment between denosumab and romosozumab is unclear. We utilised a novel overlapping strategy in three patients with very-high fracture risk despite long-term denosumab which led to greater bone density improvements than previously reported with standard approaches. Larger confirmatory prospective studies are needed.
OBJECTIVE: In patients with severe osteoporosis, the optimal approach for sequential treatment between denosumab and romosozumab has not been established. The ideal strategy would maximise gains in bone mineral density (BMD) with romosozumab and effectively mitigate the risk of rebound increased bone turnover when sequencing from denosumab. Limited studies exploring the sequence from denosumab to romosozumab report only modest-to-no improvement in BMD and inadequate suppression of rebound bone turnover.
METHODS: We describe three patients with severe osteoporosis and multiple fragility fractures despite long-term denosumab. A novel overlapping sequential treatment approach was utilised to maximise therapeutic benefit given these patients had a very high fracture risk. Romosozumab was commenced 3 months after the last denosumab dose. Instead of waiting until completion of romosozumab, denosumab was recommenced 6 months after commencing romosozumab in response to rising bone turnover markers.
RESULTS: Patients experienced a ~ 5-22% increase in lumbar spine BMD, and one patient had an 8% increase in total hip BMD after 12 months romosozumab. Serum bone turnover markers demonstrated an anabolic effect of romosozumab occurred despite overlapping treatment with denosumab. Recommencement of denosumab suppressed an increase in bone resorption in all cases. No new vertebral fractures occurred during this treatment.
CONCLUSIONS: A novel overlapping sequential treatment approach between denosumab and romosozumab produced greater improvements in lumbar spine and hip BMD than previously reported with standard approaches. Larger prospective controlled studies are needed to confirm these findings and establish the optimal use of romosozumab in patients pre-treated with denosumab to maximise BMD gains and minimise fracture risk.