Comparison of cost and complications of primary total hip arthroplasty versus oncologic proximal femur replacement.

Aims and objective: Proximal femur replacement (PFR) is most commonly performed after a large resection of the proximal femur to remove tumor and is known to have high complication rates and worse function than a primary total hip replacement (THA). Many surgeons feel that current billing practices fail to adequately differentiate this procedure from a THA. This study aims to examine patients undergoing a primary THA or oncologic PFR and compare the relative economic impact and complication rates between cohorts. Materials & methods: Patient data was queried using a national database, identifying non-pediatric patients who underwent a primary THA or oncologic PFR. Exclusionary criteria were implemented, resulting in two cohorts, each with 380 patients matched in a 1:1 manner controlling for age, gender, and Charlson Comorbidity Index. Utilizing 2022 billing data, oncologic PFRs generated an average of 41.03 RVUs and primary THAs generated 19.60 RVUs. Total hospital cost was used to generate a cost:RVU ratio for each cohort. Key systemic and joint complication rates were additionally compared between cohorts. Results: The oncologic PFR cohort had significantly higher 90-day rates of anemia, deep vein thrombosis, and prosthetic dislocation compared to the primary THA cohort. The 90-day median hospital cost for oncologic PFR was $28,562.21 with a cost:RVU ratio of $696:1. The corresponding median hospital cost for primary THA was $9667.72, with a cost:RVU ratio of $493:1. Conclusion: Hospitals incur more cost per RVU for an oncologic PFR than a primary THA. Relative to primary THA, reimbursement for oncologic PFR is under-evaluated.

Quadriceps angle as an outcome measure for structural integrity following total knee arthroplasty in individuals with severe knee osteoarthritis.

Purpose: Total knee arthroplasty (TKA) is routinely performed for pain relief and to improve performance of the knee in individuals with severe knee osteoarthritis (OA). The quadriceps angle (Q-angle) is a key component of knee joint stability. However, there is a dearth of literature evaluating Q-angle as an outcome measure after TKA in individuals with severe knee OA. Objectives: The objective of the study was to assess the Q-angle as an outcome measure before and after TKA and to find the correlation of Q-angle with pain, quadriceps strength, and knee flexion range of motion (ROM) after TKA in individuals with severe knee OA. Methods: The Q-angles of 34 individuals (male: female = 17:17) were measured using standardized procedures. Pain, quadriceps strength, and knee flexion ROM were measured. The measurements were taken preoperatively (one day before surgery), and postoperatively at the sixth week and third month after TKA. Results: The mean Q-angle was 19.17° (SD = 1.92°) before TKA, 16.06° (SD = 1.87°) at the sixth week and 13.43° (SD = 1.77°) at the third month after TKA. Significant linear correlations were noted between the Q-angle and pain, quadriceps strength, and knee flexion ROM following TKA. Conclusion: The Q-angle was measured before and after TKA using a standardized clinical goniometric method. Understanding the Q-angle before and after TKA and its relationship with various clinical and functional variables is imperative in clinical practice for orthopedic surgeons and rehabilitation professionals.

A comparison of dislocation risk between dual mobility and traditional constructs used in proximal femoral replacement.

Background: Proximal femoral replacement (PFR) is a reconstruction technique after tumor resection or for revision of failed total hip arthroplasty (THA). However, despite acceptable long-term oncologic and functional outcomes, extensive soft tissue or bone loss increases the risk for prosthetic instability. Instability may depend on the construct chosen for reconstruction, with current options including bipolar, constrained, or dual mobility implants. Clinical studies comparing patient outcomes after PFR with these three different constructs are limited. Methods: This study retrospectively examined a single tertiary academic institution's experience with PFR over a fifteen-year period. The medical records of patients who underwent PFR for indications such as tumor and failed THA with bone loss were reviewed. Patients were stratified into cohorts based on use of bipolar, constrained, or dual mobility implants. Patient demographics, disease characteristics, perioperative data, and data on prosthetic dislocations were recorded. ANOVA and chi-square testing was performed for continuous and categorical variables, respectively. The threshold for statistical significance was set to p < 0.05. Results: 106 patients were identified who underwent PFR. 46 underwent PFR with bipolar prosthesis (follow-up: 20 ± 24.57 months), 42 with constrained liner (follow-up: 30.45 ± 35.32 months), and 18 with dual mobility (follow-up: 15.38 ± 15.67 months). Only BMI (p = 0.036) and smoking history (P = 0.002) differed between groups. Dislocations occurred in 4 (8.7 %) patients who underwent reconstruction with bipolar prosthesis, compared to 8 (19.0 %) with constrained liner, and 3 (16.7 %) patients with dual mobility. Mean time to dislocation was significantly longer in dual mobility patients (P = 0.009). There were no differences in instances of early dislocation between groups (P = 00.238). Conclusion: While study numbers are low, mean time to dislocation was significantly longer with dual mobility. Additional large-scale longitudinal studies are needed to fully elucidate the differences in outcomes amongst these three treatments.

Chiral Symmetry Breaking in Colloidal Metal Nanoparticle Solutions by Circularly Polarized Light.

Shape symmetry breaking in the formation of inorganic nanostructures is of significant current interest. It was typically achieved through the growth of colloidal nanoparticles with adsorbed chiral molecules. Photochemical processes induced through asymmetric plasmon excitation by circularly polarized light in surface immobilized nanostructures also led to symmetry breaking. Here, we show that chiral symmetry breaking can be achieved by randomly rotating gold@silver core-shell nanobars in colloidal solution using circularly polarized illumination, where orientational averaging does not eliminate the symmetry breaking of an asymmetric plasmon-induced galvanic replacement reaction. Different morphological effects that are produced by circularly vs linearly polarized light illumination demonstrate the intricate effect of light polarization on the localized plasmonic-induced photochemical response. The essential features of this symmetry breaking, such as illumination wavelength dependence, were reproduced by simulations of circularly polarized light-excited-plasmon-induced hot-electron generation as the source for asymmetric metal deposition. The symmetry breaking becomes smaller in more symmetric geometrical shapes, such as triangular nanoprisms and nanocubes, and down to zero in spherical ones. The degree of symmetry breaking rises when the nanobars are immobilized on a substrate and illuminated from a single direction.

Plant-based protein emulsions with soy protein isolate and gluten improve freeze-thaw stability and shelf life of pork meatballs.

This study investigated the effects of oil-in-water emulsions used as fat substitutes on the physicochemical properties of meatballs during frozen storage. Different formulations of fat replacers were prepared, including pork fat as the control (C), oil and water (OW), oil-in-water emulsion (E), emulsion with soy protein isolate (SE), emulsion with gluten (GE), and emulsion with soy protein isolate and gluten (SG). These fat substitutes were applied to a meatball paste. The samples were stored at -18 °C for 30 and 60 days, and their physicochemical properties were analyzed after thawing at 4 °C for 12 h. The SE formulation had the highest values for both water content and liquid holding capacity during frozen storage (P < 0.05). SE, GE, and SG showed significantly higher hardness, cohesiveness, springiness, gumminess, and chewiness than those of E during storage (P < 0.05). The vegetable protein addition treatments maintained a compact structure throughout storage. SE, GE, and SG prevented lipid and protein oxidation during frozen storage. These results demonstrated that SE, GE, and SG offer significant advantages in improving the freeze-thaw stability, liquid holding capacity, and oxidation stability of pork meatballs during long-term frozen storage. Therefore, our study suggest that plant-based protein emulsions can effectively replace animal fats while maintaining product quality, offering valuable implications for the meat processing industry.

Production of active human iduronate-2-sulfatase (IDS) enzyme in Nicotiana benthamiana.

Many strategies have been developed to produce high levels of biologically active recombinant proteins in plants for biopharmaceutical purposes. However, the production of an active form of human iduronate-2-sulfatase (hIDS) for the treatment of Hunter syndrome by enzyme replacement therapy (ERT) is challenging due to the requirement for cotranslational modification by a formylglycine-producing enzyme encoded by sulfatase modifying factor 1 (hSUMF1) at the Cys84 residue, which converts it to C(alpha)-formylglycine. In this study, we have shown that hIDS can be highly expressed in N. benthamiana by using different constructs. Among them, BiP-GB1-L-dCBD1-2L-8xHis-L-6xHis-3L-EK-hIDS-HDEL (GB1-CBD1-hIDS) showed a high expression level when transiently co-expressed with the turnip crinkle virus gene silencing suppressor P38 and GB1-fused human calreticulin (GB1-CRT1) as a folding enhancer. The hSUMF1 was co-expressed with hIDS for cotranslational modification. The full-length recombinant proteins were purified using Ni2+-NTA affinity resin followed by enterokinase treatment to obtain tag-free hIDS. The N-terminal fragment was removed using microcrystalline cellulose (MCC) beads. The purified active form of hIDS can successfully cleave the sulfate group from an artificial substrate, 4-nitrocatechol sulfate, at a similar level to commercial hIDS expressed in animal cells. These results suggest that plants could be a promising platform for the production of recombinant hIDS.

Clinical and Radiographic Outcomes of Cervical Disc Replacement Versus Posterior Endoscopic Cervical Decompression: A Matched-Pair Comparison Analysis.

OBJECTIVE: To compare clinical and radiographic outcomes between 2 motion preservation surgeries, cervical disc replacement (CDR) and posterior endoscopic cervical decompression (PECD), for unilateral cervical radiculopathy. METHODS: Between February 2018 and December 2020, 60 patients with unilateral cervical radiculopathy who underwent either CDR or PECD were retrospectively recruited as matched pairs. Clinical outcomes included visual analogue scale (VAS) scores for neck and arm pain, Neck Disability Index (NDI), and satisfaction rates. The radiographic outcome was index level motion. Intraoperative data, complications, and hospital stay were collected. Preoperative and postoperative outcomes were compared. RESULTS: Patients undergoing CDR or PECD were included, with 30 cases in each group. Matched pairs were compared in terms of demographic data and preoperative measurements. CDR was associated with shorter operative times, whereas PECD resulted in less intraoperative blood loss. The total complication rate was 5%. NDI and VAS for neck and arm were significantly improved in both groups, with no significant differences between the 2 groups. Satisfaction rates of good and excellent exceeded 87% in both groups. CDR was superior to PECD in the restoration of disc height. Early postoperative follow-up showed no significant difference in terms of index level motion. PECD demonstrated significantly shorter hospital stays and quicker return-to-work times (p<0.05). CONCLUSION: PECD achieved equivalent clinical and radiologic outcomes compared with CDR when the certain criteria for surgery were met. Both techniques demonstrated the potential to maintain index level motion. Additionally, PECD resulted in less blood loss, shorter hospital stays, and faster return-to-work times. Conversely, CDR offered shorter operative times and better restoration of disc height.

Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosis.

Enzyme replacement therapy (ERT) using velmanase alfa previously showed promising efficacy and safety outcomes for up to 4 years of therapy in patients with alpha-mannosidosis. This pooled analysis from two multicenter, open-label phase IIIb extension trials rhLAMAN-07 (N = 13; NCT01908712) and rhLAMAN-09 (N = 8; NCT01908725) evaluated the long-term effects of velmanase alfa. Sixteen patients who previously completed phase I-III rhLAMAN-02/-03/-04/-05/-08 trials and five ERT-naïve patients were enrolled. Patients received 1 mg/kg velmanase alfa once weekly. Endpoints included changes from treatment baseline (before initial dose of velmanase alfa in any trial) in serum oligosaccharides, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function (forced vital capacity [FVC], % predicted), serum immunoglobulin G (IgG) levels, and adverse events. The overall cohort comprised 21 patients, divided by age at treatment baseline into pediatric (n = 14) and adult subgroups (n = 7). Distance walked according to 6MWT increased or stabilized in pediatric patients, while in adults either stabilization or slight decline was observed. Similarly, pediatric patients performed better in the 3MSCT. Changes in FVC, % predicted, were comparable in both subgroups up to ~6 years of observation, diverging thereafter. Overall, sustained serum oligosaccharide clearance and serum IgG level increase was observed upon treatment initiation and persisted until last common observation. Velmanase alfa treatment was generally well tolerated, with the majority of reported adverse events being of mild-to-moderate intensity. With follow-up of up to 12 years, long-term efficacy and safety outcomes indicate continued benefits of velmanase alfa in patients with alpha-mannosidosis.

A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies.

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

Outcomes of Left Atrioventricular Valve Operation following Atrioventricular Septal Defect Repair.

OBJECTIVES: Left atrioventricular valve (LAVV) operation following repair of atrioventricular septal defects (AVSD) can be challenging. We sought to describe characteristics and outcomes of patients requiring LAVV operation. METHODS: Retrospective review of AVSDs requiring LAVV operation between 2000-2020. Patients who experienced adverse events (AEs; defined as the need for a LAVV reoperation (repair or replacement) or death) were compared to patients without AEs. Freedom from adverse events was displayed using the Kaplan-Meier method. Reoperation and death were characterized in terms of cumulative incidence function, estimated using competing risk models. RESULTS: Of 843 patients with AVSD repaired, 59 (7.3%) required a LAVV operation and 7 (9%) valve replacement. A simple repair (cleft closure and/or annuloplasty) occurred in 26 (48.1%) and complex repair using multiple techniques in 28 (51.8%) cases. Eleven patients (20%) required further LAVV reoperation; 3 replacement of mechanical valve, 6 new valve replacement (2 Melody, 4 Mechanical) and 2 re-repair. The cumulative incidence of freedom from AE was 84.1% (75.0%, 94.2%), 78.3% (68.2%, 90.0%), 73.4% (62.2%, 86.7%), 69.7% (57.5%, 84.7%) at 1, 5, 10 and 15 years respectively. Cox univariable regression showed smaller weight (p=0.027) and early need for LAVV operation (p=0.02) were associated with AEs while cleft closure (p = 0.003) was protective against AEs. The estimated cumulative incidence of reoperation was higher in complex repairs (17.3% (7.8%, 38.7%) vs 0.5% (NA, NA) at 1 year. Greys p = 0.02). In a comparison of eras (2000-2009, 2010- 2020) there was no difference in AE (Greys p = 0.96). CONCLUSIONS: Adverse outcomes following LAVV reoperation remain common. Smaller infants, those requiring earlier reoperation and complex type repairs are at highest risk. Future studies should focus on which high risk LAVVs are more suited to early LAVV replacement.

Artificial Intelligence Improves Prediction of Major Adverse Cardiovascular Events in Patients Undergoing Transcatheter Aortic Valve Replacement Planning CT.

RATIONALE AND OBJECTIVES: Coronary CT angiography (CCTA) is mandatory before transcatheter aortic valve replacement (TAVR). Our objective was to evaluate the efficacy of artificial intelligence (AI)-powered software in automatically analyzing cardiac parameters from pre-procedural CCTA to predict major adverse cardiovascular events (MACE) in TAVR patients. MATERIALS AND METHODS: Patients undergoing pre-TAVR CCTA were retrospectively included. AI software automatically extracted 34 morphologic and volumetric cardiac parameters characterizing the ventricles, atria, myocardium, and epicardial adipose tissue. Clinical information and outcomes were recorded from institutional database. Cox regression analysis identified predictors of MACE, including non-fatal myocardial infarction, heart failure hospitalization, unstable angina, and cardiac death. Model performance was evaluated with Harrell's C-index, and nested models were compared using the likelihood ratio test. Manual analysis of 170 patients assessed agreement with automated measurements. RESULTS: Among the 648 enrolled patients (77 ± 9.3 years, 58.9% men), 116 (17.9%) experienced MACE within a median follow-up of 24 months (interquartile range 10-40). After adjusting for clinical parameters, only left ventricle long axis shortening (LV-LAS) was an independent predictor of MACE (hazard ratio [HR], 1.05 [95% confidence interval, 1.05-1.11]; p = 0.04), with significantly improved C-index (0.620 vs. 0.633; p < 0.001). When adjusted for the Society of Thoracic Surgeons Predicted Risk of Mortality score, LV-LAS was also predictive of MACE (HR, 1.08 [95%CI, 1.03-1.13]; p = 0.002), while improving model performance (C-index: 0.557 vs. 0.598; p < 0.001). All parameters showed good or excellent agreement with manual measurements. CONCLUSION: Automated AI-based comprehensive cardiac assessment enables pre-TAVR MACE prediction, with LV-LAS outperforming all other parameters.

Short and long-term outcomes of arterial and caval replacement during postchemotherapy retroperitoneal lymph node dissection in metastatic testicular cancer.

BACKGROUND AND OBJECTIVE: For patients with metastatic testicular cancer undergoing retroperitoneal lymph node dissection (RPLND), the burden of metastatic disease can require consideration for resection and replacement of major vessels despite chemotherapy. We aimed to clarify the outcomes for patients undergoing these major vascular procedures in a modern era. METHODS: Between 2000 and 2020, 2,054 patients with metastatic testicular cancer underwent a PC-RPLND; of those men, 41 also underwent an aortic, iliac, and/or inferior vena cava (IVC) resection. For men who required a vascular resection, clinicopathologic and operative details were collected. Kaplan-Meier curves were generated to estimate overall survival. RESULTS: The median preoperative mass size was 9cm in the retroperitoneum. Viable malignancy or teratoma was present in 85% of resected specimens. Following PC-RPLND and vascular resection, 22 (54%) patients recurred. The median (IQR) time to relapse was 4.6 (2.5-8.0) months. 18 (44%) patients died of disease. The overall complication rate was 56%. Ten (24%) patients had Clavien-Dindo III/IV complications, with 2 postoperative mortalities. The median overall survival was 14.9 months. Among the 41 patients, 18 patients had re-operative PC-RPLND and vascular resection; the re-operative PC-RPLND patients had significantly worse survival compared to initial attempt at PC-RPLND (9.3 vs. 162 months, P = 0.03). CONCLUSIONS: The overall survival rate for patients undergoing PC-RPLND with resection of the aorta, IVC, and/or iliac artery is 45% at 2 years. For patients with limited treatment options, these complex surgeries may offer survival benefit with an acceptable morbidity profile.

Edoxaban pharmacokinetics during in vitro continuous renal replacement therapy.

BACKGROUND: To evaluate the clearance of edoxaban during modeled in vitro continuous renal replacement therapy (CRRT), assess protein binding and circuit adsorption, and provide initial dosing recommendations. METHODS: Edoxaban was added to the CRRT circuit and serial pre-filter bovine blood samples were collected along with post-filter blood and effluent samples. All experiments were performed in duplicate using continuous veno-venous hemofiltration (CVVH) and hemodialysis (CVVHD) modes, with varying filter types, flow rates, and point of CVVH replacement fluid dilution. Concentrations of edoxaban and urea were quantified via liquid chromatography-tandem mass spectrometry. Plasma pharmacokinetic parameters for edoxaban were estimated via noncompartmental analysis. Two and three-way analysis of variance (ANOVA) models were built to assess the effects of mode, filter type, flow rate, and point of dilution on CLCRRT. Linear regression was utilized to provide dosing estimations across CRRT effluent flow rates from 0.5 to 5 L/h. Optimal edoxaban doses were suggested using CLCRRT and population non-renal clearance (CLNR) to estimate total clearance and match the systemic AUC associated with efficacy in the treatment of venous thromboembolism. RESULTS: Edoxaban clearance from the CRRT circuit occurred primarily via hemofilter adsorption to the HF1400 and M150 filters at 74% and 65%, respectively, while mean percent protein binding was 41%. Multivariate analyses confirmed the lack of influence of CRRT mode, filter type, and point of dilution on the CLCRRT of edoxaban allowing dosing recommendations to be made based on effluent flow rate. Edoxaban doses of 30-45 mg once daily were estimated to achieve target the AUC threshold for flow rates from 0.5 to 5 L/h. CONCLUSION: For CRRT flow rates most employed in clinical practice, an edoxaban dose of 45 mg once daily is predicted to achieve target systemic exposure thresholds for venous thromboembolism treatment. The safety and efficacy of this proposed dosing warrants further investigation in clinical studies.

Transcatheter aortic valve replacement in a bicuspid aortic valve with membranous interventricular septum aneurysm communicating with aortic root: a case report.

Background: Membranous interventricular septum aneurysm (MISA) is a rare abnormality occurring in 0.3% of patients with congenital heart disease, which thereby increases anatomical complexity. Case summary: Transcatheter aortic valve replacement (TAVR) procedure was planned for a 71-year-old female patient from East Asia with a type 1 bicuspid aortic valve diagnosed with severe aortic stenosis by transthoracic echocardiography (TTE). Pre-procedural multidetector computed tomography (MDCT) clearly revealed an extremely horizontal aorta and a MISA originating from the sub-annulus with the upper edge extending 7.2 mm above the annulus. A probable communicating flow between the left ventricle and the aorta was confirmed by reviewing the TTE images. Moreover, there was a calcified raphe between the left- and right-coronary cusps. A downsized balloon-expandable valve (a 23 mm Sapien 3 valve with an additional 2 mL dilation) was therefore chosen and deployed with a 100/0 aortic/ventricular ratio position. The TTE post-implantation indicated a trace perivalvular leakage. The cardiac MDCT performed post-procedure, at the 6-month, and 12-month follow-ups demonstrated complete sealing and significant healing of the aneurysm. Discussion: Transcatheter aortic valve replacement utilizing a balloon-expandable valve was successfully performed for a case with membranous interventricular septum aneurysm extending above the annulus. Comprehensive imaging analysis before the procedure is crucial for TAVR with challenging anatomical conditions.

Population Pharmacokinetics of Tigecycline for Critically Ill Patients Undergoing Continuous Renal Replacement Therapy.

Background: Tigecycline is considered one of the last resorts for treating infections caused by multidrug-resistant bacteria. Continuous renal replacement therapy (CRRT) is widely used in critically ill patients, especially those with acute kidney injury or severe infections. However, pharmacokinetic data for tigecycline in patients receiving CRRT are limited. Methods: This was a single-center prospective clinical study with intensive sampling that included critically ill patients who received tigecycline and CRRT. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis, visual predictive checks, and numerical predictive checks. Pharmacokinetic/pharmacodynamic target attainment and cumulative fraction of response analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT. Results: In total, 21 patients with 167 concentrations were included. A two-compartment model adequately described the tigecycline concentration-time points, but no covariates were found to adequately explain the viability in the pharmacokinetic parameters of tigecycline. The typical values of CL, Q, V1 and V2 were 4.42 L/h, 34.8 L/h, 30.9 L and 98.7 L, respectively. For most infections, the standard regimen of 50 mg/12 h was deemed appropriate, expect for skin and soft skin tissue infections and community-acquired pneumonia caused by Acinetobacter baumannii and Klebsiella pneumoniae, which required a dosage regimen of 100 mg/12 h or higher. Conclusion: A tigecycline PPK model describing critically ill patients undergoing CRRT was successfully developed. The optimized dosage regimens for various infections are recommended.

Total Femoral Replacement in Periprosthetic Femur Fracture: A Case Report.

Total femur replacement (TFR) is one of the most extensive endoprosthetic reconstruction procedures. The most common indication for the use of total femoral replacement is limb salvage in malignant bone tumors of the femur. This procedure is rarely performed outside the paradigm of oncological limb reconstruction. With the increased incidence of total hip and total knee replacements, complications of these procedures are also on the rise. Cases of complicated revision arthroplasties with severe bone loss, infection, and comminuted periprosthetic fractures may not have adequate residual bone stock for satisfactory fixation of megaprosthesis. With limited reconstruction options, most of these cases are offered lower limb amputation. TFR can be used as a limb salvage option in place of amputation in such cases. There have been a few case reports of TFR for non-oncological indications in the literature. We present a case of periprosthetic comminuted distal femur fracture with a loose megaprosthesis following a road traffic accident (RTA), which was managed with TFR. At four years of follow-up, the patient showed good radiological as well as clinical outcomes.

Primary ovarian insufficiency: update on clinical and genetic findings.

Primary ovarian insufficiency (POI) is a disorder of insufficient ovarian follicle function before the age of 40 years with an estimated prevalence of 3.7% worldwide. Its relevance is emerging due to the increasing number of women desiring conception late or beyond the third decade of their lives. POI clinical presentation is extremely heterogeneous with a possible exordium as primary amenorrhea due to ovarian dysgenesis or with a secondary amenorrhea due to different congenital or acquired abnormalities. POI significantly impacts non only on the fertility prospect of the affected women but also on their general, psychological, sexual quality of life, and, furthermore, on their long-term bone, cardiovascular, and cognitive health. In several cases the underlying cause of POI remains unknown and, thus, these forms are still classified as idiopathic. However, we now know the age of menopause is an inheritable trait and POI has a strong genetic background. This is confirmed by the existence of several candidate genes, experimental and natural models. The most common genetic contributors to POI are the X chromosome-linked defects. Moreover, the variable expressivity of POI defect suggests it can be considered as a multifactorial or oligogenic defect. Here, we present an updated review on clinical findings and on the principal X-linked and autosomal genes involved in syndromic and non-syndromic forms of POI. We also provide current information on the management of the premature hypoestrogenic state as well as on fertility preservation in subjects at risk of POI.

Solitary Fibrous Tumor Requiring Abdominal Aortic Vessel Replacement.

Solitary fibrous tumors (SFTs) are mesenchymal tumors, and retroperitoneal occurrence is rare. It has been identified in a variety of soft tissues and organs, such as the pleura, peritoneum, and meninges. In this case, the tumor was in contact with the abdominal aorta, and the invasion was difficult to judge preoperatively. Intraoperatively, it was revealed that the tumor could not be completely removed without aortic replacement. Although SFTs have a generally good prognosis, certain factors, such as tumor incomplete resection, have been reported to increase the risk of recurrence and metastasis. We were able to completely remove the tumor by performing a combined resection of the aorta. The specimens were microscopically disorganized proliferation of spindle-shaped cells. Immunostaining was positive for cluster of differentiation 34 (CD34) and signal transducer and activator of transcription 6 (STAT6). The tumor cells infiltrating into aortic adventitia were observed. This is a valuable case in which artificial blood vessel replacement was able to reduce the risk of recurrence and metastasis due to tumor remnants. We report a rare case of SFT resected with artificial blood vessel replacement.

A Case Report on Advanced Hip Tuberculosis: Outcomes of Combined Surgical and Rehabilitative Intervention.

Although rare, musculoskeletal involvement of tuberculosis (TB) sustains this disease as a global health problem. Hip TB presents some unique challenges to its diagnosis and cure because of its specific anatomical and biomechanical properties. Herein, we would like to highlight an integrated approach in the surgical intervention and rehabilitation towards the management of an advanced symptom-bearing 25-year-old female hip TB patient. She had taken treatment for tuberculosis, but even then, her right hip was painful, and movements were severely restricted. Imaging revealed severe destruction of the hip joint; a bone biopsy confirmed tuberculous osteomyelitis of the hip joint. Total hip replacement (THR) revealed the severe destruction of the hip joint by imaging and was found positive by bone biopsy for tuberculous osteomyelitis. The rehabilitation after the surgery consisted of measures for pain control, mobility training exercises, muscle strengthening, and balance training exercises. After six weeks of THR, the patient showed considerable improvement in pain level, flexibility, muscle strength, and functional status during assessments. What is highlighted is the complexity that lies in the management of TB of the hip, which requires the multidisciplinary approach that the case above calls for. In the future, more sophisticated diagnostics and newer therapies should be patient-reported and outcome-oriented. Larger multicenter studies directed to the various populations would be beneficial in this direction. The small size of the study, its single-center dimension, and the short follow-up limited broader applicability and long-term insights.