Decompression and collagen wrapping of a fibrolipomatous hamartoma of the median nerve: a new approach for a rare and difficult problem.

Fibrolipomatous hamartoma is a rare benign slow growing fibrofatty tumor of peripheral nerves of unknown etiology. Clinical presentation may mimic carpal tunnel syndrome when involving the median nerve. We present a case of FLH of the median nerve in a 59-year-old female treated with decompression and collagen nerve wrapping.

Case Presentation: Functional Assessment of a CASR Variant Identified in a Patient with Hypercalcaemia Confirms Familial Hypocalciuric Hypercalcaemia in the Patient and a Sister Previously Misdiagnosed with Primary Hyperparathyroidism.

Background: Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcaemia (FHH) are common causes of hypercalcaemia. Patients are mostly asymptomatic in the case of FHH and often so in the case of PHPT. In addition, biochemical parameters show considerable overlap, making differential diagnosis difficult. Genetic screening for inactivating variants in the calcium-sensing receptor (CASR) gene that are causative of FHH assists with the diagnosis since such variants are not generally associated with PHPT. However, novel CASR variants must undergo functional assessment before they can be definitively assigned a causative role in FHH. Case Presentations. We describe a 73-year-old female (patient A) who presented with mild parathyroid hormone (PTH)-dependent hypercalcaemia and a history of osteoporosis. Family history revealed that her sister (patient B) had presented a decade earlier with symptoms of PHPT including a history of mild hypercalcaemia and multiple renal calculi, prompting parathyroid surgery. However, a subtotal parathyroidectomy did not resolve her hypercalcaemia long term. On this basis, genetic screening was performed on patient A. This identified a heterozygous variant in the CASR, NM_000388.4:c.T101C: p.Leu34Pro (L34P). Functional analysis showed that the L34P variant was unable to produce mature, dimerized receptor and did not respond to Ca++ ions. Adopting American College of Medical Genetics-based guidelines, the variant was classified as 'Pathogenic (II)'. Patient B was subsequently found to carry the L34P variant heterozygously, confirming a diagnosis of FHH, not PHPT. Conclusion: This study shows the importance of examining patient's family history in providing clues to the diagnosis in isolated cases of hypercalcaemia. In this case, history of a sister's unsuccessful parathyroidectomy prompted genetic screening in a patient who might otherwise have undergone inappropriate parathyroid surgery. Screening detected an inactivating CASR variant, firming up a diagnosis of FHH. These studies reaffirm the requirement for functionally assessing novel CASR variants prior to assigning causality to FHH.

Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Insulinoma Presenting With Postprandial Hypoglycemia in a Pregnant Woman With MEN-1.

Insulinomas are rare insulin-secreting tumors of pancreatic origin that cause hypoglycemia and can be associated with multiple endocrine neoplasia type 1 (MEN1). While rare, they are the most common cause of hypoglycemia related to endogenous hyperinsulinism. A 28-year-old woman with known MEN1 presented with postprandial hypoglycemia in the second trimester of pregnancy. Prior to her presentation she was known to have several pancreatic neuroendocrine tumors that had been stable on serial imaging, but no history of hypoglycemia. She was managed with dietary intervention during pregnancy and gave birth to a healthy baby at 37 weeks' gestation. After pregnancy, hypoglycemia initially resolved, but then recurred at 8 months post partum. Magnetic resonance imaging showed several pancreatic neoplasms with the largest lesion measuring 29 mm in the pancreatic tail, unchanged from previous imaging. After localization with a selective arterial calcium stimulation test, the patient underwent successful distal pancreatectomy with resolution of symptoms. This case is unusual in that her initial presentation was during pregnancy, she had predominantly postprandial rather than fasting hypoglycemia, and her symptoms remitted for several months after delivery. Key learning points are to have a low index of suspicion for an insulinoma when there is a history of MEN1 and the need for a pragmatic approach to diagnosis and treatment during pregnancy.

Three Cases of Non-islet Cell Tumor Hypoglycemia Highlighting Efficacy of Glucocorticoid Treatment.

Non-islet cell tumor hypoglycemia (NICTH) is a rarely encountered cause of hypoglycemia. It is most often caused by tumor secretion of precursor insulin-like growth factor-2 (IGF-2) which, in high concentrations, binds to insulin receptors exerting insulin-like metabolic effects. It is often associated with mesenchymal and hepatic tumors. We describe 3 cases of NICTH: a 60-year-old man with an unresectable pelvic sarcoma and two women ages 43 and 57 with metastatic hemangiopericytoma. Biochemical assessment identified hypoglycemia associated with suppressed insulin, c-peptide, and beta-hydroxybutyrate levels. Each patient was treated with oral glucocorticoids, which effectively prevented recurrence of hypoglycemia and this effect was sustained long-term. These cases highlight a rarely encountered but important cause of hypoglycemia and demonstrate the long-term efficacy of glucocorticoid treatment in preventing hypoglycemia in cases of NICTH related to surgically unresectable tumors.

The optimal healthy ranges of thyroid function defined by the risk of cardiovascular disease and mortality: systematic review and individual participant data meta-analysis.

BACKGROUND: Reference intervals of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are statistically defined by the 2·5-97·5th percentiles, without accounting for potential risk of clinical outcomes. We aimed to define the optimal healthy ranges of TSH and FT4 based on the risk of cardiovascular disease and mortality. METHODS: This systematic review and individual participant data (IPD) meta-analysis identified eligible prospective cohorts through the Thyroid Studies Collaboration, supplemented with a systematic search via Embase, MEDLINE (Ovid), Web of science, the Cochrane Central Register of Controlled Trials, and Google Scholar from Jan 1, 2011, to Feb 12, 2017 with an updated search to Oct 13, 2022 (cohorts found in the second search were not included in the IPD). We included cohorts that collected TSH or FT4, and cardiovascular outcomes or mortality for adults (aged ≥18 years). We excluded cohorts that included solely pregnant women, individuals with overt thyroid diseases, and individuals with cardiovascular disease. We contacted the study investigators of eligible cohorts to provide IPD on demographics, TSH, FT4, thyroid peroxidase antibodies, history of cardiovascular disease and risk factors, medication use, cardiovascular disease events, cardiovascular disease mortality, and all-cause mortality. The primary outcome was a composite outcome including cardiovascular disease events (coronary heart disease, stroke, and heart failure) and all-cause mortality. Secondary outcomes were the separate assessment of cardiovascular disease events, all-cause mortality, and cardiovascular disease mortality. We performed one-step (cohort-stratified Cox models) and two-step (random-effects models) meta-analyses adjusting for age, sex, smoking, systolic blood pressure, diabetes, and total cholesterol. The study was registered with PROSPERO, CRD42017057576. FINDINGS: We identified 3935 studies, of which 53 cohorts fulfilled the inclusion criteria and 26 cohorts agreed to participate. We included IPD on 134 346 participants with a median age of 59 years (range 18-106) at baseline. There was a J-shaped association of FT4 with the composite outcome and secondary outcomes, with the 20th (median 13·5 pmol/L [IQR 11·2-13·9]) to 40th percentiles (median 14·8 pmol/L [12·3-15·0]) conveying the lowest risk. Compared with the 20-40th percentiles, the age-adjusted and sex-adjusted hazard ratio (HR) for FT4 in the 80-100th percentiles was 1·20 (95% CI 1·11-1·31) for the composite outcome, 1·34 (1·20-1·49) for all-cause mortality, 1·57 (1·31-1·89) for cardiovascular disease mortality, and 1·22 (1·11-1·33) for cardiovascular disease events. In individuals aged 70 years and older, the 10-year absolute risk of composite outcome increased over 5% for women with FT4 greater than the 85th percentile (median 17·6 pmol/L [IQR 15·0-18·3]), and men with FT4 greater than the 75th percentile (16·7 pmol/L [14·0-17·4]). Non-linear associations were identified for TSH, with the 60th (median 1·90 mIU/L [IQR 1·68-2·25]) to 80th percentiles (2·90 mIU/L [2·41-3·32]) associated with the lowest risk of cardiovascular disease and mortality. Compared with the 60-80th percentiles, the age-adjusted and sex-adjusted HR of TSH in the 0-20th percentiles was 1·07 (95% CI 1·02-1·12) for the composite outcome, 1·09 (1·05-1·14) for all-cause mortality, and 1·07 (0·99-1·16) for cardiovascular disease mortality. INTERPRETATION: There was a J-shaped association of FT4 with cardiovascular disease and mortality. Low concentrations of TSH were associated with a higher risk of all-cause mortality and cardiovascular disease mortality. The 20-40th percentiles of FT4 and the 60-80th percentiles of TSH could represent the optimal healthy ranges of thyroid function based on the risk of cardiovascular disease and mortality, with more than 5% increase of 10-year composite risk identified for FT4 greater than the 85th percentile in women and men older than 70 years. We propose a feasible approach to establish the optimal healthy ranges of thyroid function, allowing for better identification of individuals with a higher risk of thyroid-related outcomes. FUNDING: None.

Orthopaedic knee scooter-related injury: prevalence and patient safety perception in a prospective cohort with exploratory risk factor analysis.

BACKGROUND: There is a paucity of research investigating the harms associated with orthopaedic knee scooter (OKS) use and patient safety perceptions. This prospective study aimed to define the prevalence of OKS-related injuries, describe the patient perceptions of OKS safety, and identify potential risk factors. METHODS: This study was conducted at a single foot and ankle fellowship-trained surgeon's community-based clinic from 6/2020 to 4/2021 and enrolled 134 patients. Our primary outcome was an OKS-related event (injury or fall) and informed an a priori power analysis. Point estimate of association magnitude was calculated as an odds ratio (OR) for statistically and clinically significant associations. RESULTS: There were 118 (88%) patients eligible for analysis; fourteen enrolled patients did not use OKS, and two withdrew. The prevalence of patient falls was 37% (44/118), and the prevalence of patient injury was 15% (18/118). Four percent of patients would not recommend OKS and 8% would not use an OKS again. Sedentary lifestyle increased risk (OR = 4.67, 1.52-14.35 95 CI) for OKS-related injury. CONCLUSIONS: Despite a high prevalence of patient falls (37%), there is a low prevalence of injury (15%) and a favorable perception of OKS safety. Sedentary lifestyles may be a risk factor for OKS-related injury and should be considered in the development of a risk model.

Mitigating Spinal Cord Stimulator Lead Migration Complications in Minimally Invasive Spine Surgery: Technical Note.

Spinal Cord Stimulators (SCS) are a nonpharmacologic chronic pain management treatment modality that is well-validated and cost-effective within the surgeon's armamentarium. The reported complication rates are between 5.3% to 40%, most commonly secondary to mechanical hardware failure. The most common mechanical complication is lead migration, which necessitates second surgery. The purpose of this technical note is to describe a minimally invasive spine surgery (MISS) implantation technique we believe to be more resilient to lead migration. We present a stepwise technique for SCS implantation with a maxillofacial screw and washer failsafe.

Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis.

BACKGROUND: Adequate maternal thyroid function is important for an uncomplicated pregnancy. Although multiple observational studies have evaluated the association between thyroid dysfunction and hypertensive disorders of pregnancy, the methods and definitions of abnormalities in thyroid function tests were heterogeneous, and the results were conflicting. We aimed to examine the association between abnormalities in thyroid function tests and risk of gestational hypertension and pre-eclampsia. METHODS: In this systematic review and meta-analysis of individual-participant data, we searched MEDLINE (Ovid), Embase, Scopus, and the Cochrane Database of Systematic Reviews from date of inception to Dec 27, 2019, for prospective cohort studies with data on maternal concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid peroxidase (TPO) antibodies, individually or in combination, as well as on gestational hypertension, pre-eclampsia, or both. We issued open invitations to study authors to participate in the Consortium on Thyroid and Pregnancy and to share the individual-participant data. We excluded participants who had pre-existing thyroid disease or multifetal pregnancy, or were taking medications that affect thyroid function. The primary outcomes were documented gestational hypertension and pre-eclampsia. Individual-participant data were analysed using logistic mixed-effects regression models adjusting for maternal age, BMI, smoking, parity, ethnicity, and gestational age at blood sampling. The study protocol was registered with PROSPERO, CRD42019128585. FINDINGS: We identified 1539 published studies, of which 33 cohorts met the inclusion criteria and 19 cohorts were included after the authors agreed to participate. Our study population comprised 46 528 pregnant women, of whom 39 826 (85·6%) women had sufficient data (TSH and FT4 concentrations and TPO antibody status) to be classified according to their thyroid function status. Of these women, 1275 (3·2%) had subclinical hypothyroidism, 933 (2·3%) had isolated hypothyroxinaemia, 619 (1·6%) had subclinical hyperthyroidism, and 337 (0·8%) had overt hyperthyroidism. Compared with euthyroidism, subclinical hypothyroidism was associated with a higher risk of pre-eclampsia (2·1% vs 3·6%; OR 1·53 [95% CI 1·09-2·15]). Subclinical hyperthyroidism, isolated hypothyroxinaemia, or TPO antibody positivity were not associated with gestational hypertension or pre-eclampsia. In continuous analyses, both a higher and a lower TSH concentration were associated with a higher risk of pre-eclampsia (p=0·0001). FT4 concentrations were not associated with the outcomes measured. INTERPRETATION: Compared with euthyroidism, subclinical hypothyroidism during pregnancy was associated with a higher risk of pre-eclampsia. There was a U-shaped association of TSH with pre-eclampsia. These results quantify the risks of gestational hypertension or pre-eclampsia in women with thyroid function test abnormalities, adding to the total body of evidence on the risk of adverse maternal and fetal outcomes of thyroid dysfunction during pregnancy. These findings have potential implications for defining the optimal treatment target in women treated with levothyroxine during pregnancy, which needs to be assessed in future interventional studies. FUNDING: Arkansas Biosciences Institute and Netherlands Organization for Scientific Research.

Clinical outcomes in the surgical management of ankle fractures: A systematic review and meta-analysis of fibular intramedullary nail fixation vs. open reduction and internal fixation in randomized controlled trials.

BACKGROUND: What level I evidence exists to support the use of FNF for surgical management of ankle fractures in high risk patients? The purpose of this study was to compare clinical outcomes following fibular intramedullary nail fixation (FNF) and open reduction and internal fixation (ORIF) of ankle fractures. METHODS: A systematic review of the current literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Certainty of evidence reported according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Our primary hypothesis was that patients undergoing FNF procedures to manage an ankle fracture would have significantly higher patient reported outcome scores (PROs) than patients undergoing ORIF. Primary study outcome measures were validated PROs. Secondary outcome measures included complication rate, secondary surgery rate, and bony union. RESULTS: The primary outcome analysis revealed no evidence of a significant effect difference on Olerud and Molander Ankle Score (OMAS) PRO and no evidence of statistical heterogeneity. Secondary outcome analysis revealed a significant 0.30 (0.12-0.74 95CI) relative risk reduction for complications in FNF (P = 0.008). No evidence of an effect difference for bony union. The GRADE certainty of the evidence was rated as low for bone union. No evidence of reporting bias was appreciated. Sensitivity analyses did not significantly alter effect estimates. CONCLUSION: This systematic review and meta-analysis restricted to evidence derived from RCTs revealed that the quality of evidence is reasonably strong and likely sufficient to conclude: (1) there is likely no clinically important difference between FNF and ORIF up to 12 months post-operatively, as defined by OMS (moderate certainty); (2) surgeons may reasonably expect reduced complications in 14 out of every 100 patients treated with FNF (moderate certainty); (3) there is likely no difference in bony union (low certainty). Future studies should investigate more patient-centered outcomes and if short-term findings are durable over time if these findings apply to lower risk populations. LEVEL OF EVIDENCE: Systematic review and meta-analysis of level I evidence.

Prospective Associations of Sugar-Sweetened Beverage Consumption During Adolescence with Body Composition and Bone Mass at Early Adulthood.

BACKGROUND: Adolescents have a higher consumption of sugar-sweetened beverages (SSBs) than other age groups, but little is known of the impact of SSB intake during adolescence on body composition and bone mass in early adulthood. OBJECTIVES: Associations of SSB intake from 14 to 20 y with fat, lean, and bone mass at 20 y of age were evaluated. METHODS: Study participants were 1137 offspring (562 females) from the Raine Study. Food intake, including SSB consumption in servings/d (1 serving = 250 mL), was estimated using FFQs at 14, 17, and 20 y of age. DXA scanning at 20 y measured whole body fat mass, lean mass, and bone mineral content (BMC). Using latent class growth analysis, 4 SSB intake trajectory classes were identified: consistently low (n = 540, intakes mostly <0.5 serving/d), increasing (n = 65), decreasing (n = 258), and consistently high (n = 274, intakes mostly >1.3 servings/d). RESULTS: Median total SSB intake was 0.8, 0.7, and 0.5 serving/d, and median carbonated SSB intake was 0.3, 0.3, and 0.4 serving/d at 14, 17, and 20 y, respectively. Mean ± SD BMI (in kg/m2) was 23.9 ± 4.2 at 20 y. After adjustment for covariates including sex, demographic, energy intake, and maternal factors, individuals with "consistently high" SSB consumption had significantly higher total body fat mass at 20 y than those with "consistently low" consumption (23.3 ± 0.6 compared with 21.2 ± 0.4 kg, P = 0.004), which remained significant after further adjustment for "Healthy" and "Western" dietary patterns (23.2 ± 0.6 compared with 21.2 ± 0.4 kg, P = 0.011). No significant associations were observed between SSB intake trajectory classes and lean body mass or BMC at 20 y. CONCLUSIONS: In this cohort, consistently higher consumption of SSBs in adolescence and early adulthood are associated with increased fat mass but not with bone mass at 20 y of age.

The SQSTM1/p62 UBA domain regulates Ajuba localisation, degradation and NF-κB signalling function.

The LIM-domain containing protein Ajuba and the scaffold protein SQSTM1/p62 regulate signalling of NF-κB, a transcription factor involved in osteoclast differentiation and survival. The ubiquitin-associated domain of SQSTM1/p62 is frequently mutated in patients with Paget's disease of bone. Here, we report that Ajuba activates NF-κB activity in HEK293 cells, and that co-expression with SQSTM1/p62 inhibits this activation in an UBA domain-dependent manner. SQSTM1/p62 regulates proteins by targeting them to the ubiquitin-proteasome system or the autophagy-lysosome pathway. We show that Ajuba is degraded by autophagy, however co-expression with SQSTM1/p62 (wild type or UBA-deficient) protects Ajuba levels both in cells undergoing autophagy and those exposed to proteasomal stress. Additionally, in unstressed cells co-expression of SQSTM1/p62 reduces the amount of Ajuba present in the nucleus. SQSTM1/p62 with an intact ubiquitin-associated domain forms holding complexes with Ajuba that are not destined for degradation yet inhibit signalling. Thus, in situations with altered levels and localization of SQSTM1/p62 expression, such as osteoclasts in Paget's disease of bone and various cancers, SQSTM1/p62 may compartmentalize Ajuba and thereby impact its cellular functions and disease pathogenesis. In Paget's, ubiquitin-associated domain mutations may lead to increased or prolonged Ajuba-induced NF-κB signalling leading to increased osteoclastogenesis. In cancer, Ajuba expression promotes cell survival. The increased levels of SQSTM1/p62 observed in cancer may enhance Ajuba-mediated cancer cell survival.

Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3.

OBJECTIVE: Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental vs genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance. METHODS: Heritability of thyroid-stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9-16.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7 522 526 SNPs as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (n = 1115) followed by meta-analysis to maximise power for discovery. RESULTS: Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7-74.9%) for TSH, 67.5% (59.8-75.3%) for fT4, 59.7% (54.4-65.0%) for fT3 and 48.8% (40.6-56.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of NCOA3 and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near NCOA3, and fT3 and rs12687280 near SERPINA7. Gene-based association analysis highlighted SERPINA7 for fT3 and NPAS3 for fT4. CONCLUSION: Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.

Prevalence and patterns of multimorbidity in Australian baby boomers: the Busselton healthy ageing study.

BACKGROUND AND OBJECTIVE: Chronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults. METHODS: Participants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. RESULTS: The individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0-13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) "Healthy" (70%) with average of 1.95 conditions; 2) "Respiratory and Atopy" (11%, 3.65 conditions); 3) "Non-cardiometabolic" (14%, 4.77 conditions), and 4) "Cardiometabolic" (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. CONCLUSION: Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.

A Single-Center 10-Year Retrospective Analysis of Cryoablation for the Management of Desmoid Tumors.

PURPOSE: To determine the efficacy and safety of cryoablation in patients with desmoid tumors (DTs) retrospectively over a 10-year period at a single institution. MATERIALS AND METHODS: Between February 25, 2010, and February 25, 2020, 25 patients (age, 12-80 years) with 26 lesions (mean preprocedural tumor volume was 237 cm3) were treated over 44 cryoablation procedures. Eleven patients were treated with first-line therapy. Fourteen patients had previous medical therapy, radiotherapy, and/or surgery. Subsequent clinical follow-up, imaging outcomes, and safety were analyzed for technical success, change in total lesion volume (TLV) and viable tumor volume (VTV), modified response evaluation criteria in solid tumors (mRECIST), progression-free survival (PFS) for tumor progression and symptom recurrence, symptom improvement, and procedure-related complications. Symptomatic improvement was defined as documentation of relief of pain (partial or complete) and/or functional impairment. RESULTS: All procedures were technically successful. At 7-12 months, median changes in TLV and VTV were -6.7% (P = .809) and -43.7% (P = .01), respectively. At 10-12 months, the mRECIST responses were complete response, 0%; partial response, 61.5% (8/13); stable disease, 30.8% (4/13); and progressive disease, 7.7% (1/13). The median PFS for tumor progression and symptom recurrence were not reached, with a median follow-up of 15.3 and 21.0 months, respectively. Symptomatic relief (partial or complete) was achieved in 96.9% (32/33) of patients. One major complication was noted (2.4%). CONCLUSIONS: In this retrospectively identified cohort, cryoablation was effective and safe for the local control of extra-abdominal DTs in short-term follow-up.

Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests.

INTRODUCTION: Discordant thyroid function tests are routinely encountered in clinical practice. Differential diagnoses include acute thyroxine (T4) ingestion, laboratory interference from heterophilic antibodies, thyroid hormone resistance, thyroid-stimulating hormone (TSH)-secreting pituitary adenomas, and T4 protein binding abnormalities. The impact of abnormal binding proteins may be less recognized since widespread use of free T4 (FT4) assays compared to older total T4 assays. CASE REPORT: A 69-year-old female was referred for assessment of discordant thyroid function tests. Biochemistry since July 2015 showed persistently elevated FT4 levels by immunoassay ranging between 25 to 34 pmol/L with normal or slightly decreased TSH ranging between 0.05 to 2.74 mU/L. The patient was clinically euthyroid on 100 mcg daily of levothyroxine for Hashimoto's thyroiditis. FT4 measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was 19.5 pmol/L. Exome sequencing (confirmed by Sanger sequencing) detected a guanine to adenine substitution at residue 725 of the ALB gene previously associated with dysalbuminemic hyperthyroxinemia. The patient's daughter had similar thyroid function tests and the same genetic variant. FT4 results from 3 different automated immunoassays showed the Roche Cobas and Siemens Centaur platforms to be most affected by the variant, and Abbott Architect had the best agreement with LC-MS/MS. CONCLUSION: Familial dysalbuminemic hyperthyroxinemia is a potential cause of discordant thyroid function tests. Clinicians suspecting protein-binding abnormalities may further investigate using reference methods such as LC-MS/MS and equilibrium dialysis if available. The increasing accessibility of exome sequencing offers a cost-effective method of diagnosing genetic variants that cause discordant thyroid function tests.

Development of a Predictive Algorithm for Symptomatic Hip Abductor Tears in Patients Undergoing Primary Hip Arthroscopy.

BACKGROUND: Patients presenting with lateral hip pain may pose a difficult diagnostic challenge, as pain can be due to various causes. PURPOSE/HYPOTHESIS: The purpose was to identify risk factors and predictors for symptomatic hip abductor tears in a cohort of patients undergoing primary hip arthroscopy for femoroacetabular impingement syndrome. We hypothesized that body mass index (BMI), female sex, age, and presence of chondral damage would be significant predictors of hip abductor pathologies. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Data were prospectively collected and retrospectively reviewed. Patients were included if they underwent primary hip arthroscopy between March 2009 and December 2019. Patients with Tönnis grade >1, previous hip conditions, incomplete radiographic data, or open procedures were excluded. All demographic variables, intraoperative measurements, and radiographic measurements were assessed using a bivariate analysis. A stepwise logistic regression was used to determine predictive variables. RESULTS: In total, 255 hips with a hip abductor tear that underwent hip arthroscopy and 2106 hips without a tear that underwent hip arthroscopy were included. The stepwise logistic regression successfully created a predictive model using age, sex, BMI, lateral joint space, and alpha angle as variables. The efficiency of the predictive model was 90.7%, with an area under the curve of 0.894. The odds of having a hip abductor tear were 7.41 times higher in females (odds ratio [OR], 7.41; 95% CI, 4.61-11.9). Each additional year of age was associated with a 13.7% (OR, 1.137; 95% CI, 1.12-1.16) increase in the odds of having a tear. Similarly, with each 1-unit increase in BMI, the odds of having a tear increased by 3.4% (OR, 1.034; 95% CI, 1.01-1.06). CONCLUSION: This study successfully created a predictive model that identified female sex (OR, 7.41), increasing age (OR, 1.137 for each year), and increased BMI (OR, 1.034 for each unit of BMI) as significant independent predictors of the presence of hip abductor tears in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome. This model can be used in support of physical examination and imaging suggestive of hip abductor pathology to preoperatively identify the probability of a symptomatic hip abductor tear in these patients.

Short-term Clinical Outcomes of Robotic-Arm Assisted Total Hip Arthroplasty: A Pair-Matched Controlled Study.

Advances have made robotic assistance a viable option in total hip arthroplasty (THA). However, the clinical outcomes of this procedure relative to manual THA are limited in the literature. This study compared robotic-arm assisted (RAA) THA and manual THA at minimum 2-year follow-up. Data were collected prospectively on all THAs performed from July 2011 to January 2015. Patients were included if they underwent RAA primary THA for idiopathic osteo-arthritis and had minimum follow-up of 2 years. The following patient-reported outcomes were compared: Harris Hip Score (HHS), Forgotten Joint Score (FJS-12), visual analog scale (VAS) pain score, and satisfaction. Postoperative radio-graphs were analyzed for cup inclination, cup version, leg-length discrepancy, and global offset. Robotic-arm assisted THA patients were matched 1:1 with manual THA patients for age, sex, body mass index, and surgical approach. Each study group included 85 patients. There were no significant differences in the demographic factors between the groups. Both HHS and FJS-12 were significantly higher in the RAA group at minimum 2-year follow-up. The VAS score was lower in the RAA group, but this difference was not statistically significant. A significantly higher proportion of patients were in the Lewinnek and Callanan safe zones for cup orientation. There was no difference between the groups in patient satisfaction. Robotic-arm assisted THA yielded improved short-term patient outcomes compared with manual THA and higher likelihood of cup placement in the safe zones. No differences were found regarding VAS scores, patient satisfaction, complication rates, or subsequent revisions between groups. [Orthopedics. 2021;44(2):e236-e242.].

Teamwork in hip preservation: the ISHA 2019 Annual Scientific Meeting.

Hip preservation surgery is now an established part of orthopedic surgery and sports medicine. This report describes the key findings of the 11th Annual Scientific Meeting of International Society for Hip Arthroscopy-the International Hip Preservation Society-in Madrid, Spain from 16 to 19 October 2019. Lectures, seminars and debates explored the most up-to-date and expert views on a wide variety of subjects, including: diagnostic problems in groin pain, buttock pain and low back pain; surgical techniques in acetabular dysplasia, hip instability, femoroacetabular impingement syndrome, labral repair and reconstruction, cartilage defects, adolescent hips and gluteus medius and hamstring tears; and new ideas about femoral torsion, hip-spine syndrome, hip capsule surgery, impact of particular sports on hip injuries, registries, robotics and training for hip preservation specialists. Surgeons, sports physicians, radiologists and physiotherapists looking after young people with hip problems have an increasingly sophisticated armoury of ideas and techniques with which to help their patients. The concept of hip preservation has developed incredibly fast over the last decade; now it is clear that the best results can only be achieved by a multidisciplinary team working together. The 2020s will be the decade of 'Teamwork in Hip Preservation'.