Endoscopic techniques for early diagnosis of cloacal pathologies and sex determination in blue spotted tree monitor (Varanus macraei) and Cuming's water monitor (Varanus cumingi).

This article attempts to present, for the first time, the usefulness and feasibility of using endoscopic techniques in the cloacal region of Varanus cumingi and Varanus macraei. This method can serve both diagnostic and therapeutic purposes, as well as offering an early approach to sex determination through the observation of the urodeum which in males ends in a blind end while in females it consists of two ostia which represent the outlets of the oviducts. In this context, commonly employed sex determination techniques, such as post-cloacal spur detection, have shown unreliability. The study involved the examination of ten specimens, approximately one year old, from a private breeding farm, following a complete clinical evaluation to confirm their general state of health. All subjects underwent sedation, which allowed the evaluation of anatomical structures, the health status of the cloaca and the determination of sex. This study and its findings may provide a critical basis for addressing population declines of these species, particularly for V. macraei, which has already been classified as 'endangered' by the IUCN.

Greater Postoperative Biceps Tendon Migration Following Biceps Tenodesis Correlates with Lower Patient Reported Outcomes Scores.

PURPOSE: To assess the relationship between tendon migration, as measured by radiostereometric analysis (RSA), and patient-reported outcome measures (PROMs) following biceps tenodesis (BT); to determine the likelihood of achieving clinically significant outcomes (CSOs) following BT; and to identify factors that impact CSO achievement. METHODS: Patients undergoing arthroscopic suprapectoral or open subpectoral BT at a single, high-volume academic medical center were prospectively enrolled. A tantalum bead sutured to the tenodesis construct was utilized as a radio-opaque marker. Biceps tendon migration was measured on calibrated radiographs at 12 weeks postoperatively. PROMs (Constant-Murley score [Constant], Single Assessment Numeric Evaluation [SANE], and Patient-Reported Outcomes Measurement Information Systemic-Upper Extremity [PROMIS-UE]) were collected preoperatively and at ≥2 years follow-up. RESULTS: Of 115 patients enrolled, 94 (82%) patients were included (median age=52 years and BMI=31.4 kg/m2). At a mean follow-up of 2.9 years, median Constant, SANE, and PROMIS-UE were 33 (interquartile range [IQR]=26-35), 90 (IQR=80-99), and 47 (IQR=42-58), respectively. Median tantalum bead migration was 6.5 mm (IQR 1.8-13.8). There was a significant correlation between migration and Constant (r2 = 0.222, beta= -0.554, 95% CI -1.027- [-0.081], P=0.022), SANE (r2 = 0.238, beta= -0.198, 95% CI -0.337 - [-0.058], P=0.006) and PROMIS-UE (r2 = 0.233, beta= -0.406, 95% CI -0.707 - [-0.104], P=0.009). In univariable analysis, higher BMI was associated with achievement of substantial clinical benefit (SCB, unadj-OR=1.078, 95%CI 1.007-1.161, P=0.038). Greater bead migration was negatively associated with achievement of minimal clinically important difference (MCID, unadj-OR=0.969, 95% CI 0.943-0.993, P=0.014) and patient acceptable symptomatic state (PASS, unadj-OR 0.965, 95% CI 0.937-0.989, P=0.008) on all 3 instruments. CONCLUSION: A 1 cm-increase in tenodesed biceps tendon migration was associated with a decrease in Constant, SANE, and PROMIS-UE of 6, 2, and 4 points, respectively, at a mean of 2.9 years after surgery. Most patients achieved clinically significant outcomes (CSOs) for these PROMs by latest follow-up, and greater biceps tendon construct migration was negatively associated with the likelihood of CSO achievement. LEVEL OF EVIDENCE: IV, retrospective case series.

Profiling severe asthma: Any relevance for age? An analysis from Severe Asthma Network Italy (SANI) cohort.

Background: Aging implies changes in terms of lung function, immune system, and respiratory and extra-respiratory comorbidities. Few studies have specifically addressed the relevance of age on severe asthma burden and control. We aimed to evaluate whether age acts as an independent determinant of asthma severity, in terms of clinical, functional, and inflammatory profile, and to explore potential cofactors that contribute to a more difficult disease control in different age groups. Methods: Patients from Severe Asthma Network Italy (SANI) registry were retrospectively divided in subgroups according to their age. Cutoffs for age were established according to quartiles in order to obtain a comparable number of patients for each group, and then rounded for the sake of simplicity. Results: Overall, 1805 severe asthma patients were analyzed. Lung function represented the most important age-related variable. On the opposite the level of asthma control was not differently distributed among age ranges. In young people the presence of atopy-related comorbidities (allergic rhinitis, atopic dermatitis) predominated, whilst systemic-metabolic and degenerative comorbidities such as diabetes, cardiovascular diseases, anxious-depressive syndrome, and osteoporosis prevailed in elderly. Bronchiectasis and sleep disturbances were significantly associated with age. Conclusions: Despite that it cannot be considered a treatable trait, our study suggests that age should be evaluated within a personalized approach to severe asthma patients, in order to provide a better clinical profiling and a more tailored treatment strategy.

Hydroxyurea mobile directly observed therapy versus standard monitoring in patients with sickle cell anemia: a phase 2 randomized trial.

BACKGROUND: Sickle cell anemia (SCA) prevalence remains high in sub-Saharan Africa. Long-term treatment with hydroxyurea (HU) increases survival, however, poor adherence to treatment could limit effectiveness. Whilst HU treatment adherence is currently high, this might decrease over time. METHODS: We conducted a single-center, randomized, open-label, parallel group phase 2 controlled clinical trial to determine whether mobile Directly Observed Therapy (m-DOT) increases HU treatment adherence (NCT02844673). Eligible participants were adults with homozygous SCA. People on a chronic blood transfusion program, with hemoglobin (Hb) A levels greater than 20% of the total Hb, total Hb less than 4 g/dL, pregnant or HIV positive were excluded. After a 3-month pre-treatment period participants were randomized to either m-DOT or standard monitoring arm. All participants received smart mobile phones and were treated with HU (15 mg/kg) daily for three months. In the m-DOT arm, drug intake was video recorded on cell phone by the participant and the video sent to the study team. The primary objective was to evaluate the effect of m-DOT on adherence to HU treatment by medication possession ratio (MPR). RESULTS: Of the 86 participants randomized, 76 completed the trial (26.13 ± 6.97 years, 63.5 % female). Adherence was high (MPR > 95 %) in both groups, 29 (80.6 %) in m-DOT versus 37 (94.9 %) in the standard monitoring arm (P = 0.079). No HU treatment was withheld from participants due to safety concerns. CONCLUSIONS: m-DOT did not increase adherence to HU treatment. We recommend that further testing in larger trials with a longer follow up period be undertaken.

Sickle cell anemia (SCA) is an inherited blood disorder in which there is an abnormal protein inside red blood cells. This results in red blood cells becoming sickle shaped and more easily destroyed in the body. Long-term treatment with hydroxyurea can reduce the frequency of illness and hospitalization. However, often people do not manage to take their medication regularly when treatment is long-term. We therefore investigated whether people with SCA in sub-Saharan Africa are more likely to take hydroxyurea when they are remotely monitored than when they are not. Remote monitoring did not improve adherence. However, our study is small and was undertaken over a short time period when hydroxyurea had only recently become available to people with SCA. We propose further studies, to see if remote monitoring increases medication adherence in people with SCA in other scenarios.

Total Knee Arthroplasty in Patients with Cerebral Palsy: A Large Database Analysis.

Cerebral palsy (CP) is a neurodevelopmental condition that can result in altered gait biomechanics, joint dysfunction, and imbalance. The complications associated with total knee arthroplasty (TKA) in patients with CP have not yet been well described. Therefore, our analysis sought to compare the 90-day and 2-year complications following TKA in patients with and without CP. The PearlDiver Mariner database was utilized to identify patients with CP undergoing primary TKA between 2010 and 2020. This cohort was matched 1:4 to a control cohort without neurodegenerative disorders based on age, sex, Elixhauser Comorbidity Index (ECI), tobacco use, obesity, and diabetes. A total of 3,257 patients (657 CP patients 2,600 controls) were included in our final analysis. A multivariable logistic regression analysis was utilized to determine the risk of CP on medical and surgical complications at 90 days and all-cause revision rates at 2 years. Patients with CP had an increased risk of acute kidney injury (odds ratio [OR]: 1.66; 95% confidence interval [CI]: 1.07-2.5; p = 0.019), pneumonia (OR: 5.63; 95% CI: 3.69-8.67; p < 0.001), urinary tract infection (OR: 5.01; 95% CI: 3.85-6.52; p < 0.001), and transfusion (OR: 2.21; 95% CI: 1.50-3.23; p < 0.001). CP patients additionally had a higher incidence of emergency department (ED) visits (OR: 5.24; 95% CI: 3.76-7.32; p < 0.001) and readmissions (OR: 5.24; 95% CI: 2.57-4.96; p < 0.001). There were no differences in rates of periprosthetic joint infection (PJI; OR: 1.23; 95% CI: 0.69-2.10; p = 0.463), surgical site infection (SSI; OR: 0.51; 95% CI: 0.12-1.46; p = 0.463), and reoperation (OR: 1.35; 95% CI: 0.71-2.43; p = 0.339) at 90 days postoperatively. The all-cause revision rates at 2 years were comparable (OR: 1.02; 95% CI: 0.67-1.51; p = 0.927). In this database review, we found that CP patients have a higher risk of medical complications in the acute postoperative period following TKA. The 90-day surgical complication and 2-year revision rates in CP patients were comparable to matched controls.

Hyperbolic Shear Metasurfaces.

Polar dielectrics with low crystal symmetry and sharp phonon resonances can support hyperbolic shear polaritons, which are highly confined surface modes with frequency-dependent optical axes and asymmetric dissipation features. So far, these modes have been observed only in bulk natural materials at midinfrared frequencies, with properties limited by available crystal geometries and phonon resonance strength. Here, we introduce hyperbolic shear metasurfaces, which are ultrathin engineered surfaces supporting hyperbolic surface modes with symmetry-tailored axial dispersion and loss redistribution that can maximally enhance light-matter interactions. By engineering effective shear phenomena in these engineered surfaces, we demonstrate geometry-controlled, ultraconfined, low-loss hyperbolic surface waves with broadband Purcell enhancements applicable across a broad range of the electromagnetic spectrum.

Is Hospital-Based Outpatient Revision Total Knee Arthroplasty Safe? An Analysis of 2,171 Outpatient Aseptic Revision Procedures.

BACKGROUND: Outpatient primary total knee arthroplasty (TKA) has been well-established as a safe and effective procedure; however, the safety of outpatient revision TKA remains unclear. Therefore, this study utilized a large database to compare outcomes between outpatient and inpatient revision TKA. METHODS: An all-payor database was queried to identify patients undergoing revision TKA from 2010 to 2022. Patients who had diagnosis codes related to periprosthetic joint infection (PJI) were excluded. Outpatient surgery was defined as a length of stay < 24 hours. Cohorts were matched by age, sex, Elixhauser Comorbidity Index, comorbidities (diabetes, obesity, tobacco use), components revised (1-versus 2-component), and revision etiology. Medical complications at 90 days and surgical complications at 1 and 2 years postoperatively were evaluated through multivariate logistic regression. A total of 4,342 aseptic revision TKAs were included. RESULTS: No differences in patient characteristics, procedure type, or revision etiologies were seen between groups. The outpatient cohort had a lower risk of PJI (odds ratio (OR): 0.547, 95% confidence interval (CI): 0.337 to 0.869; P = .012), wound dehiscence (OR: 0.393, 95% CI: 0.225 to 0.658; P < .001), transfusion (OR: 0.241, 95% CI: 0.055 to 0.750; P = .027), reoperation (OR: 0.508, 95% CI: 0.305 to 0.822; P = .007), and any complication (OR: 0.696, 95% CI: 0.584 to 0.829; P < .001) at 90 days postoperatively. At 1 year and 2 years postoperatively, outpatient revision TKA patients had a lower incidence of revision for PJI (OR: 0.332, 95% CI: 0.131 to 0.743; P = .011 and OR: 0.446, 95% CI; 0.217 to 0.859; P = .020, respectively) and all-cause revision (OR: 0.518, 95% CI: 0.377 to 0.706; P < .001 and OR: 0.548, 95% CI: 0.422 to 0.712; P < .001, respectively). CONCLUSIONS: Our findings suggest that revision TKA can be safely performed on an outpatient basis in appropriately selected patients who do not have an increased risk of adverse events relative to inpatient revision TKA. However, we could not ascertain case complexity in either cohort, and despite controlling for several potential confounders, other less tangible differences could exist between groups.

Early Prosthetic Hip Dislocation: Does the Timing of the Dislocation Matter?

BACKGROUND: Early dislocation following total hip arthroplasty (THA) is a common reason for revision. The purpose of this study was to determine if the acuity of the dislocation episode affects the risk of revision surgery. METHODS: A retrospective review of a national, all-payer administrative database comprised of claims from 2010 to 2020 was used to identify patients who had a prosthetic hip dislocation at various postoperative time intervals (0 to 7, 7 to 30, 30 to 60, and 60 to 90 days). Of the 45,352 primary unilateral THA patients who had sufficient follow-up, there were 2,878 dislocations within 90 days. Dislocators were matched 1:1 based on age, sex, and a comorbidity index with a control group (no dislocation). Demographics, surgical indications, comorbidities, ten-year revision rates, and complications were compared among cohorts. Multivariable logistic regression analysis was performed to identify risk factors for revision THA following early dislocation. RESULTS: Among matched cohorts, dislocation at any time interval was associated with significantly increased odds of subsequent 10-years revision (OR [odds ratio] = 25.60 to 33.4, P < .001). Acute dislocators within 7 days did not have an increased risk of all cause revisions at 10 years relative to other early dislocators. Revision for indication of instability decreased with time to first dislocation (<7 days: 85.7% versus 60 to 90 days: 53.9%). Primary diagnoses of posttraumatic arthritis (OR = 2.53 [1.84 to 3.49], P < .001), hip fracture (OR = 3.8 [2.53 to 5.72], P < .001), and osteonecrosis (OR = 1.75 [1.12 to 2.73], P = .010) were most commonly associated with revision surgery after an early dislocation. CONCLUSIONS: Dislocation within 90 days of THA is associated with increased odds of subsequent revision. Early dislocation within 7 days of surgery has similar all cause revision-free survivorship, but an increased risk of a subsequent revision for instability when compared to patients who dislocated within 7 to 90 days.

Utero-cervical angle to predict the risk of spontaneous preterm birth: a review of literature.

BACKGROUND: The aim of this paper was to evaluate the predictive role of the uterocervical angle (UCA) in spontaneous preterm birth (sPTB). METHODS: A systematic review of the literature was performed including all studies reporting the association between UCA and sPTB. Searches were performed with the use of a combination of keywords: "cervical length," "uterocervical angle," and "preterm birth" from inception of each database to March 2022. The statistical evaluations were carried out using the Comprehensive Meta-Analysis version 3 (Biostat Inc. USA). RESULTS: Sixteen studies all conducted on the second trimester UCA as well as its association with sPTB were included in this study. In all studies the measurements of cervical length (CL) and UCA were performer in the second trimester, except in one that in the third trimester. In most studies the CL is greater than 30 mm and the UCA is greater than 110 °. In seven studies women with symptoms were considered while in 8 studies the women were asymptomatic. CONCLUSIONS: It is too early for it to reach a firm conclusion on UCA utilization in clinical settings. A higher UCA measurement (greater than 150°) is an important risk factor for deliveries before 37 weeks' gestation. It provides a higher diagnostic performance in high risk patients than the CL measurement. However, the most relevant ultrasound parameter for the prediction of delivery within the next few data in women with preterm delivery remains the cervical length. There is a need to consider both markers and create protocols so that the values obtained with UCA and those with CL can make a real contribution to decisions to be made rather than using only CL.

Late Manipulation under Anesthesia after Total Knee Arthroplasty: Improved Range of Motion and a Low Complication Rate.

The purpose of this study was to evaluate outcomes of late manipulation under anesthesia (MUA) for stiffness performed from ≥12 weeks to more than a year after primary total knee arthroplasty (TKA). A total of 152 patients receiving MUA ≥12 weeks after primary TKA from 2014 to 2021 were reviewed. The primary outcome measured was change in range of motion (ROM). We tracked intraoperative complications and the need for repeat MUA or open procedure for continued stiffness after initial MUA. Three subgroups were analyzed: Group 1 included 58 knees between 12 weeks and 6 months after TKA, Group 2 included 44 knees between 6 and 12 months after TKA, and Group 3 included 50 knees ≥12 months after TKA. Analysis included descriptive statistics and univariate analysis, with α <0.05. Groups 1 to 3 all significantly increased their overall ROM by 20.9, 19.2, and 22.0 degrees, respectively. All groups significantly increased their flexion and extension from preoperatively. Group 1 had one intraoperative supracondylar femur fracture (1.7%) requiring open reduction and internal fixation, and five patients required repeat MUA or open procedure (8.6%). Group 2 had no intraoperative fractures, and five patients required repeat MUA or open procedure (11.4%). Group 3 had one intraoperative tibial tubercle avulsion fracture managed conservatively (2.0%) and one repeat MUA (2.0%). Late MUA resulted in significantly improved ROM in all groups. ROM improved more as the time from index TKA increased, although statistically insignificant. Repeat MUA or open procedure rate decreased with MUA ≥12 months from TKA, although statistically insignificant. The overall intraoperative fracture risk was 1.3%.

Suppression of anthracnose disease by orsellinaldehyde isolated from the mushroom Coprinus comatus.

AIMS: Anthracnose caused by Colletotrichum species is one of the most devastating diseases of fruits and crops. We isolated and identified an antifungal compound from the mushroom Coprinus comatus and investigated its inhibitory potential against anthracnose disease-causing fungi with the goal of discovering natural products that can suppress anthracnose-caused plant disease. METHODS AND RESULTS: The culture filtrate of C. comatus was subjected to a bioassay-guided isolation of antifungal compounds. The active compound was identified as orsellinaldehyde (2,4-dihydroxy-6-methylbenzaldehyde) based on mass spectroscopy and nuclear magnetic resonance analyses. Orsellinaldehyde displayed broad-spectrum inhibitory activity against different plant pathogenic fungi. Among the tested Colletotrichum species, it exhibited the lowest IC50 values on conidial germination and germ tube elongation of Colletotrichum orbiculare. The compound also showed remarkable inhibitory activity against Colletotrichum gloeosporiodes. The staining of Colletotrichum conidia with fluorescein diacetate and propidium iodide demonstrated that the compound is fungicidal. The postharvest in-vivo detached fruit assay indicated that orsellinaldehyde suppressed anthracnose lesion symptoms on mango and cucumber fruits caused by C. gloeosporioides and C. orbiculare, respectively. CONCLUSIONS: Orsellinaldehyde was identified as a potent antifungal compound from the culture filtrate of C. comatus. The inhibitory and fungicidal activities of orsellinaldehyde against different Colletotrichum species indicate its potential as a fungicide for protecting various fruits against anthracnose disease-causing fungi.

Hemoglobin scavenger receptor CD163 as a potential biomarker of hemolysis-induced hepatobiliary injury in sickle cell disease.

Sickle cell disease (SCD)-associated chronic hemolysis promotes oxidative stress, inflammation, and thrombosis leading to organ damage, including liver damage. Hemoglobin scavenger receptor CD163 plays a protective role in SCD by scavenging both hemoglobin-haptoglobin complexes and cell-free hemoglobin. A limited number of studies in the past have shown a positive correlation of CD163 expression with poor disease outcomes in patients with SCD. However, the role and regulation of CD163 in SCD-related hepatobiliary injury have not been fully elucidated yet. Here we show that chronic liver injury in SCD patients is associated with elevated levels of hepatic membrane-bound CD163. Hemolysis and increase in hepatic heme, hemoglobin, and iron levels elevate CD163 expression in the SCD mouse liver. Mechanistically we show that heme oxygenase-1 (HO-1) positively regulates membrane-bound CD163 expression independent of nuclear factor erythroid 2-related factor 2 (NRF2) signaling in SCD liver. We further demonstrate that the interaction between CD163 and HO-1 is not dependent on CD163-hemoglobin binding. These findings indicate that CD163 is a potential biomarker of SCD-associated hepatobiliary injury. Understanding the role of HO-1 in membrane-bound CD163 regulation may help identify novel therapeutic targets for hemolysis-induced chronic liver injury.

Shoulder Prosthetic Infection and Humerus Osteomyelitis From Cutibacterium Following Eden-Hybinette Procedure.

We describe the case of a patient who recently underwent a guided arthroscopic Eden-Hybinette procedure for the revision of a previous failed procedure of Latarjet and resurgence of shoulder instability. The subsequent development of painful infectious arthritis of the left shoulder complicated by osteomyelitis of the humerus, caused by Cutibacterium acnes, and accompanied by high fever was resolved only after the removal of synthetic screws and bone grafting and thanks to prolonged intravenous antibiotic treatment. The antibiotic regime was continued, both intramuscularly and orally, after discharge, allowing the full healing of the severe osteoarticular infection of the shoulder.

Outcomes after pancreaticoduodenectomy with or without preoperative hyperbaric oxygen therapy.

Background: Hyperbaric oxygen (HBO2) therapy is an alternative method against the deleterious effects of ischemic/reperfusion (I/R) injury and its inflammatory response. This study assessed the effect of preoperative HBO2 on patients undergoing pancreaticoduodenectomy. Study Design: Patients were randomized via a computer-generated algorithm. Patients in the HBO2 cohort received two sessions of HBO2 the evening before and the morning of surgery. Measurements of inflammatory mediators and self-assessed pain scales were determined pre-and postoperatively. In addition, perioperative variables and long-term survival were collected and analyzed. Data are presented as median (mean ± SD). Results: 33 patients were included; 17 received preoperative HBO2, and 16 did not. There were no intraoperative or postoperative statistical differences between patients with or without preoperative HBO2. Erythrocyte sedimentation rate (ESR), IL-6, and IL-10 increased slightly before returning to normal, while TGF-alpha decreased before increasing. However, there were no differences with or without HBO2. At postoperative day 30, the pain level measured with VAS score (Visual Analog Score) was lower after HBO2 (1 ± 1.3 vs. 3 ± 3.0, p=0.05). Eleven (76%) patients in the HBO2 cohort and 12 (75%) patients in the non- HBO2 had malignant pathology. The percentage of positive lymph nodes in the HBO2 was 7% compared to 14% in the non-HBO2 (p<0.001). Overall survival was inferior after HBO2 compared to the non- HBO2 (p=0.03). Conclusions: Preoperative HBO2 did not affect perioperative outcomes or significantly change the inflammatory mediators for patients undergoing robotic pancreaticoduodenectomy. Long-term survival was inferior after preoperative HBO2. Further randomized controlled studies are required to assess the full impact of this treatment on patients' prognosis.

Frailty as a comprehensive health measure beyond seizure control in patients with epilepsy: A cross-sectional study.

OBJECTIVE: Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features. METHODS: In this cross-sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient-reported outcomes were analyzed using general linear models and Spearman correlation. RESULTS: The median age at the time of study visit was 47 years (interquartile range = 33-60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33-item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4-inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory-10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls. SIGNIFICANCE: This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment-related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies.

Riociguat in patients with sickle cell disease and hypertension or proteinuria (STERIO-SCD): a randomised, double-blind, placebo controlled, phase 1-2 trial.

BACKGROUND: Although nitric oxide based therapeutics have been shown in preclinical models to reduce vaso-occlusive events and improve cardiovascular function, a clinical trial of a phosphodiesterase 5 inhibitor increased rates of admission to hospital for pain. We aimed to examine if riociguat, a direct stimulator of the nitric oxide receptor soluble guanylate cyclase, causes similar increases in vaso-occlusive events. METHODS: This was a phase 1-2, randomised, double blind, placebo-controlled trial. Eligible patients were 18 years or older, had confirmed sickle cell disease documented by haemoglobin electrophoresis or HPLC fractionation (haemoglobin SS, SC, Sß-thalassemia, SD, or SO-Arab), and stage 1 hypertension or proteinuria. Participants were randomly assigned 1:1 to receive either riociguat or matching placebo via a web-based system to maintain allocation concealment. Both treatments were administered orally starting at 1·0 mg three times a day up to 2·5 mg three times a day (highest tolerated dose) for 12 weeks. Dose escalation by 0·5 mg was considered every 2 weeks if systolic blood pressure was greater than 95 mm Hg and the participant had no signs of hypotension; otherwise, the last dose was maintained. The primary outcome was the proportion of participants who had at least one adjudicated treatment-emergent serious adverse event. The analysis was performed by the intention-to-treat. This trial is registered with ClinicalTrials.gov (NCT02633397) and was completed. FINDINGS: Between April 11, 2017, and Dec 31, 2021, 165 participants were screened and consented to be enrolled into the study. Of these, 130 participants were randomly assigned to either riociguat (n=66) or placebo (n=64). The proportion of participants with at least one treatment-emergent serious adverse event was 22·7% (n=15) in the riociguat group and 31·3% (n=20) in the placebo group (difference -8·5% [90% CI -21·4 to 4·5]; p=0·19). A similar pattern emerged in other key safety outcomes, sickle cell related vaso-occlusive events (16·7 [n=11] vs 21·9% [n=14]; difference -5·2% [-17·2 to 6·5]; p=0·42), mean pain severity (3·18 vs 3·32; adjusted mean difference -0·14 [-0·70 to 0·42]; p=0·69), and pain interference (3·15 vs 3·12; 0·04 [-0·62 to 0·69]; p=0·93) at 12 weeks were similar between groups. Regarding the key clinical efficacy endpoints, participants taking riociguat had a blood pressure of -8·20 mm Hg (-10·48 to -5·91) compared with -1·24 (-3·58 to 1·10) in those taking placebo (-6·96 mm Hg (90% CI -10·22 to -3·69; p<0·001). INTERPRETATION: Riociguat was safe and had a significant haemodynamic effect on systemic blood pressure. The results of this study provide measures of effect and variability that will inform power calculations for future trials. FUNDING: Bayer Pharmaceuticals.

Three Differing Methods of Treating Intraoperative Nondisplaced Calcar Fractures Demonstrate Similar Radiographic Stem Subsidence.

BACKGROUND: Several management strategies have been described to treat intraoperative calcar fractures during total hip arthroplasty (THA), including retaining the primary implant and utilizing cerclage cables (CCs) or switching the implant to one that bypasses the fracture and achieves diaphyseal fixation. However, the radiographic and clinical outcomes of these differing strategies have never been described and compared. METHODS: We retrospectively identified 50 patients who sustained an intraoperative calcar fracture out of 9,129 primary total hip arthroplasties (0.55%) performed by one of three surgeons between 2008 and 2022. Each of the three surgeons consistently employed a distinct strategy for the management of these fractures: retention of the primary metaphyseal-engaging implant and placement of CCs; exchange to a modular, tapered-fluted stem (MTF); or exchange to a fully-coated, diaphyseal-engaging stem (FC). Stem subsidence was then evaluated on standing anteroposterior pelvis radiographs at three months and one year postoperatively. Postoperative medical and surgical complication rates were evaluated. RESULTS: A total of fifteen patients were treated with CC, 15 with MTF, and 20 with FC. At three-month follow-up, mean stem subsidence was 0.43 ± 0.08 mm, 1.47 ± 0.36 mm, and 0.68 ± 0.39 mm for CC, MTF, and FC cohorts, respectively (P = .323). At one-year, mean stem subsidence was 0.70 ± 0.08 mm, 1.74 ± 0.69 mm, and 1.88 ± 0.90 mm for the CC, MTF, and FC cohorts, respectively (P = .485). Medical complications included 2 venous thromboembolic events (4%) within 90 days of surgery. There were 6 reoperations (12%); 3 (6%) for acute periprosthetic joint infection (all within the FC cohort); 2 (4%) for postoperative periprosthetic fractures (one fracture distal to the stem in the FC cohort and one fracture at the level of the stem in the MTF cohort), and 1 (2%) closed reduction for instability (within the CC cohort). CONCLUSIONS: The three described methods of managing intraoperative nondisplaced calcar fractures demonstrated little radiographic stem subsidence; however, the risk of reoperation was much higher than expected.

Body Mass Index Does Not Drive the Risk for Early Postoperative Instability After Total Hip Arthroplasty: A Matched Cohort Analysis.

BACKGROUND: Instability remains the leading cause of revision following total hip arthroplasty (THA). The objective of the present investigation was to determine whether an elevated body mass index (BMI) is associated with an increased risk of instability after primary THA. METHODS: An administrative claims database was queried for patients undergoing elective, primary THA for osteoarthritis between 2010 and 2022. Patients who underwent THA for a femoral neck fracture were excluded. Patients who had an elevated BMI were grouped into the following cohorts: 25 to 29.9 (n = 2,313), 30 to 34.9 (n = 2,230), 35 to 39.9 (n = 1,852), 40 to 44.9 (n = 1,450), 45 to 49.9 (n = 752), and 50 to 59.9 (n = 334). Patients were matched 1:1 based on age, sex, and Elixhauser Comorbidity Index, as well as a history of spinal fusion, neurodegenerative disorders, and alcohol abuse, to controls with a normal BMI (20 to 24.9). A multivariate logistic regression controlling for age, sex, Elixhauser Comorbidity Index, and additional risk factors for dislocation was used to evaluate dislocation rates at 30 days, 90 days, 6 months, 1 year, and 2 years. Rates of revision for instability were similarly compared at 1 year and 2 years postoperatively. RESULTS: No significant differences in dislocation rate were observed between control patients and each of the evaluated BMI classes at all evaluated postoperative intervals (all P values > .05). Similarly, the risk of revision for instability was comparable between the normal weight cohort and each evaluated BMI class at 1 year and 2 years postoperatively (all P values > .05). CONCLUSIONS: Controlling for comorbidities and known risk factors for instability, the present analysis demonstrated no difference in rates of dislocation or revision for instability between normal-weight patients and those in higher BMI classes.

Warm autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurring after COVID19 infection and administration of Casirivimab + Imdevimab (COVID19 monoclonal antibody).

Warm Autoimmune Hemolytic Anemia (WAHA) is the most common form of autoimmune hemolysis and there is a growing body of evidence of an association between SARS-CoV-2 infection, WAHA and a hyperinflammatory state, including hemophagocytic lymphohistiocytosis/macrophage activation syndrome. However, there is no literature to date of WAHA or hyperinflammatory state following administration of anti-SARS-CoV-2 monoclonal antibody treatment. This report documents a case of a patient with history of WAHA who developed brisk hemolysis and a hyperinflammatory state consistent with hemophagocytic lymphohistiocytosis/macrophage activation syndrome after COVID-19 infection and treatment with an anti-SARS-CoV-2 monoclonal antibody. He was successfully treated with multimodal treatment involving steroids, intravenous immunoglobulins, rituximab, anakinra, and vincristine with resolution of the hemolysis.

Risk of Subsequent Fusion After Isolated Decompression of Lumbar Facet Cysts.

INTRODUCTION: Lumbar facet cysts represent a potential source of nerve root compression in elderly patients. Isolated decompression without fusion has proven to be a reasonable treatment option in properly indicated patients. However, the risk of lumbar fusion after isolated decompression and facet cyst excision has yet to be elucidated. METHODS: The PearlDiver database was reviewed for patients undergoing isolated laminectomy for lumbar facet cyst from January 2015 to December 2018 using Current Procedural Terminology coding. Patients undergoing concomitant fusion or additional decompression, as well as those diagnosed with preexisting spondylolisthesis or without a minimum of 5-year follow-up, were excluded. Rates of subsequent lumbar fusion and potential risk factors for subsequent fusion were identified. Statistical analysis included descriptive statistics, chi square test, and multivariate logistic regression. Results were considered significant at P < 0.05. RESULTS: In total, 10,707 patients were ultimately included for analysis. At 5-year follow-up, 727 (6.79%) of patients underwent subsequent lumbar fusion after initial isolated decompression. Of these, 301 (2.81% of total patients, 41.4% of fusion patients) underwent fusion within the first year after decompression. Multivariate analysis identified chronic kidney disease, hypertension, and osteoarthritis as risk factors for requiring subsequent lumbar fusion at 5 years following the index decompression procedure ( P < 0.033; all). CONCLUSION: Patients undergoing isolated decompression for lumbar facet cysts undergo subsequent lumbar fusion at a 5-year rate of 6.79%. Risk factors for subsequent decompression include chronic kidney disease, hypertension, and osteoarthritis. This study will assist spine surgeons in appropriately counseling patients on expected postoperative course and potential risks of isolated decompression.