More Severe Radiographic Osteoarthritis Is Associated With Increased Improvement in Patients' Health State Following a Total Knee Arthroplasty.

BACKGROUND: To assess whether preoperative radiological severity of osteoarthritis (OA) is related to the level of improvement in patients' health state measured 1 year after total knee arthroplasty (TKA). METHODS: Radiographic severity of OA was graded using the Kellgren-Lawrence (KL) classification. Two independent observers were blinded to patients' outcome scores. Health-related quality of life was measured using EQ-5D-3L preoperatively and at 12-month follow-up. The 5 dimensions of the EQ-5D were converted into a health state index score. The association between KL grade and improvement in health state score was analyzed using multiple linear regression. RESULTS: Among 156 consecutive patients (68% females, mean age 69 years) who underwent primary TKA, 3 knees (2%) were classified as KL grade 2, 115 as KL grade 3 (74%), and 38 as KL grade 4 (24%). Follow-up rate was 77%. There was substantial intra-rater and inter-rater agreement (Cohen's kappa = 0.80 and 0.79). Most patients (64%) had clinically significant improvement in their health state score 1 year after TKA. However, after adjusting for relevant covariates, patients with severe OA (KL grade 4) were found to have significantly more improvement in their health state score than patients with mild or moderate OA (KL grade 2 or 3, respectively). Separate analysis of the 5 EQ-5D dimensions showed that the KL group differences were most evident in the "usual activities" and "pain/discomfort" dimensions. CONCLUSION: Patients with severe OA have significantly more improvement in their usual activities and pain/discomfort 1 year after TKA than patients with less severe OA.

Immune Checkpoint Inhibitors in Older Adults.

Cancer is primarily a disease of older adults. The treatment of advanced stage tumors usually involves the use of systemic agents that may be associated with significant risk of toxicity, especially in older patients. Immune checkpoint inhibitors are newcomers to the oncology world with improved efficacy and better safety profiles when compared to traditional cytotoxic drugs. This makes them an attractive treatment option. While there are no elderly specific trials, this review attempts to look at the current available data from a geriatric oncology perspective. We reviewed data from phase III studies that led to newly approved indications of checkpoint inhibitors in non-small cell lung cancer, melanoma, and renal cell cancer. Data were reviewed with respect to response, survival, and toxicity according to three groups: <65 years, 65-75 years, and >75 years. Current literature does not allow one to draw definitive conclusions regarding the role of immune checkpoint inhibitors in older adults. However, they may offer a potentially less toxic but equally efficacious treatment option for the senior adult oncology patient.

No difference in patient-reported outcomes with cruciate-retaining, anterior-stabilized, and posterior-stabilized total knee arthroplasty designs.

Aims: This study compared patient-reported outcomes of three total knee arthroplasty (TKA) designs from one manufacturer: one cruciate-retaining (CR) design, and two cruciate-sacrificing designs, anterior-stabilized (AS) and posterior-stabilized (PS). Methods: Patients scheduled for primary TKA were included in a single-centre, prospective, three-armed, blinded randomized trial (n = 216; 72 per group). After intraoperative confirmation of posterior cruciate ligament (PCL) integrity, patients were randomly allocated to receive a CR, AS, or PS design from the same TKA system. Insertion of an AS or PS design required PCL resection. The primary outcome was the mean score of all five subscales of the Knee injury and Osteoarthritis Outcome Score (KOOS) at two-year follow-up. Secondary outcomes included all KOOS subscales, Oxford Knee Score, EuroQol five-dimension health questionnaire, EuroQol visual analogue scale, range of motion (ROM), and willingness to undergo the operation again. Patient satisfaction was also assessed. Results: Patients reported similar levels of pain, function, satisfaction, and general health regardless of the prosthetic design they received. Mean maximal flexion (129° (95% confidence interval (CI) 127° to 131°) was greater in the PS group than in the CR (120° (95% CI 121° to 124°)) and AS groups (122° (95% CI 120° to 124°)). Conclusion: Despite differences in design and constraint, CR, AS, and PS designs from a single TKA system resulted in no differences in patient-reported outcomes at two-year follow-up. PS patients had statistically better ROM, but the clinical significance of this finding is unclear.

Comparison of the in-vivo kinematics of three different knee prosthesis designs during a step-up movement.

BACKGROUND: There is no consensus on the importance of the kinematics of the prosthetic joint for the clinical outcome after total knee arthroplasty. A 3-armed randomized controlled trial was done to determine and compare the in vivo kinematics of a posterior cruciate-retaining and two posterior cruciate-sacrificing (Anterior-Stabilized and Posterior-Stabilized) prosthetic designs from the same total knee arthroplasty system. Since the anterior-stabilized and posterior-stabilized designs are posterior cruciate ligament-sacrificing designs, we hypothesized they would have similar contact-point kinematics. Further, we hypothesized that the cruciate-retaining design would have contact-point kinematics different from the anterior-stabilized and the posterior-stabilized designs, but comparable to a native knee. METHODS: Thirty-nine patients with a well-functioning total knee arthroplasty one year postoperatively underwent kinematic analysis of a weight-bearing step-up movement under fluoroscopic recording. Model-based radiostereometric analysis was used to determine anteroposterior contact-point translations and rotations through the movement path to assess knee kinematics. FINDINGS: The cruciate-retaining and anterior-stabilized groups' medial and lateral contact-points displayed similar paradoxical posterior translations during step-up in the magnitude of 7 and 2 mm, respectively. In contrast, the posterior-stabilized group's contact-points translated anteriorly by 4 and 10 mm throughout the movement and were significantly more posterior than the cruciate-retaining and the anterior-stabilized groups from >100° to 40° of flexion. The femur rotated internally with all designs. INTERPRETATION: The cruciate-retaining and anterior-stabilized designs displayed similar contact-point translation patterns during a step-up movement. Only the posterior-stabilized design showed a pattern comparable to native knees. Conversion from a cruciate-retaining to an anterior-stabilized design because of posterior cruciate ligament insufficiency will not change knee kinematics.

Low incidence of enterocolitis and colonic mucosal inflammation in Norwegian patients with Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HD) may be associated with inflammation in the colon. Further, the etiology of Hirschsprung-associated enterocolitis (HEC) is unclear. To learn more about these features, we examined our cohort of HD patients during a period of 6 years for inflammation in their colonic mucosa as well as for signs of HEC. MATERIALS AND METHODS: Rectal suction biopsies and operative full thickness aganglionic and ganglionic colonic specimens from 36 patients were examined. Signs of inflammation were recorded in hematoxylin/eosin/saffron (HES)-stained sections and with fluorescence conjugated polyclonal antibodies to IgA and IgG applied on serial sections. The suction biopsies were also evaluated for the presence of mucus inspissation and crypt dilatation. Clinical signs of HEC were recorded from medical files of the same 36 patients. RESULTS: HES-staining revealed that seven patients had inflammation in the suction biopsies; these patients were significantly older than the patients without inflammation. Slight mucus inspissation was identified in suction biopsies of five out of 33 patients, but crypt abscesses or ulcerations were not found in any specimens. Virtually all very young patients (<3 months) had slight crypt dilatation. We identified inflammation in resected colonic segments from 17 out of 36 patients. Thirteen of these 17 had a diverting colostomy, and only one out of 14 patients with colostomy had no inflammation. Inflammatory changes were similar in ganglionic and aganglionic bowel. By immunofluorescence (IF) staining, inflammation was found in resected colonic segments from five patients. Four of these had a colostomy. HEC was diagnosed in three patients, and inflammation detected in resected specimens from only one of these three. CONCLUSIONS: We have not been able to identify particular characteristics in the colonic or rectal mucosa that are linked to development of HEC. Inflammation in the resected specimen was mainly found in patients with a diverting colostomy, and then in both ganglionic and aganglionic colon.

[Transanal resection of colon for Hirschsprung's disease]. / Transanal colonreseksjon for Hirschsprungs sykdom.

BACKGROUND: Traditional surgical management of Hirschsprung's disease consists of a three-stage approach including proximal colostomy, definitive pull-through resection at one year of age and closure of the stoma shortly after the pull-through. At our institution, patients with this disorder have been operated with a one-stage transanal technique without laparotomy and colostomy since 2001. The early results of this procedure are presented in the article. PATIENTS AND METHODS: Complications and postoperative bowel function have been recorded after the introduction of the one-stage transanal technique. RESULTS: Transanal pull-through was intended in 20 children. Laparotomy (5 patients) and laparoscopy (1 patient) were done in 6 of the children due to technical reasons. Median weight at operation was five kg (3.5-25 kg), and a median of 25 cm of bowel (9-36 cm) were resected transanally. There were no perioperative complications. Postoperative complications included stricture (3 patients), perianal excoriations (2 patients) and severe constipation (1 patient). Short term follow up shows similar bowel habits as after laparotomy procedures. INTERPRETATION: Early results show that primary transanal pull-through in Hirschsprung's disease patients with aganglionosis to descending colon is safe. It is beneficial to avoid a colostomy and probably laparotomy.

Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer.

Prostate cancer is the second leading cause of cancer death in men in the US and Europe. The treatment of advanced-stage prostate cancer has been androgen deprivation. Medical castration leads to decreased production of testosterone and dihydrotestosterone by the testes, but adrenal glands and even prostate cancer tissue continue to produce androgens, which eventually leads to continued prostate cancer growth despite castrate level of androgens. This stage is known as castrate-resistant prostate cancer (CRPC), which continues to be a challenge to treat. Addition of androgen antagonists to hormonal deprivation has been successful in lowering the prostate-specific antigen levels further, but has not actually translated into life-prolonging options. The results of several contemporary studies have continued to demonstrate activation of the androgen receptor as being the key factor in the continued growth of prostate cancer. Blockade of androgen production by nongonadal sources has led to clinical benefit in this setting. One such agent is abiraterone acetate, which significantly reduces androgen production by blocking the enzyme, cytochrome P450 17 alpha-hydroxylase (CYP17). This has provided physicians with another treatment option for patients with CRPC. The landscape for prostate cancer treatment has changed with the approval of cabazitaxel, sipuleucel-T and abiraterone. Here we provide an overview of abiraterone acetate, its mechanism of action, and its potential place for therapy in CRPC.

Endosonographic evaluation of anal sphincters in healthy children.

PURPOSE: To describe the endosonographic anatomy of anal sphincters in healthy children and to evaluate the reproducibility of sphincter thickness measurements. METHODS: Forty-five healthy children with median age of 3.6 years (range, 1.0-14.5 years) were studied while under general anesthesia for minor surgery. Anal endosonography was performed with a 7- to 10-MHz rotating transducer with a diameter of 19 mm. The internal anal sphincter (IAS) and the external anal sphincter (EAS) were assessed by 2 independent observers. RESULTS: IAS and EAS were identified in all children. The mean thickness of IAS and EAS were 1.3 mm and 5.3 mm, respectively. Identification of the inner and outer border of IAS was difficult, especially in children younger than 3 years. The thickness of EAS was easier to assess, and the interrater reliability for EAS thickness measurements was excellent. EAS thickness was positively correlated with the children's age. Reflectivity varied within the EAS with frequent hyporeflective areas. CONCLUSIONS: Anal endosonography provided visualization of the IAS and EAS in children. Assessment of exact IAS thickness was difficult, especially in the youngest children. Mean EAS thickness was 5.3 mm, increasing with age. Hyporeflective areas of the intact EAS should not be misinterpreted as sphincter defects.