Fungal and mycobacterial cultures should not be routinely obtained for diagnostic work-up of patients with suspected periprosthetic joint infections

Aims Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative. Methods We performed a retrospective review of patients diagnosed with hip or knee PJI between 1 January 2010 and 31 December 2019, at the Mayo Clinic in Rochester, Minnesota, USA. We included patients aged 18 years or older who had fungal, mycobacterial, or both cultures performed together with bacterial cultures. Cases with positive fungal or mycobacterial cultures were reviewed using the electronic medical record to classify the microbiological findings as representing true infection or not. Results There were 2,067 episodes of PJI diagnosed within the study period. A total of 3,629 fungal cultures and 2,923 mycobacterial cultures were performed, with at least one of these performed in 56% of episodes (n = 1,157). Test positivity rates of fungal and mycobacterial cultures were 5% (n = 179) and 1.2% (n = 34), respectively. After a comprehensive review, there were 40 true fungal and eight true mycobacterial PJIs. BCB were 90% sensitive in diagnosing true fungal PJI and 100% sensitive in detecting rapidly growing mycobacteria (RGM). Fungal stains were performed in 27 true fungal PJI but were only positive in four episodes (14.8% sensitivity). None of the mycobacterial stains was positive. Conclusion Routine fungal and mycobacterial stains and cultures should not be performed as they have little clinical utility in the diagnosis of PJI and are associated with significant costs. Candida species and RGM are readily recovered using BCB. More research is needed to predict rare non- Candida fungal and slowly growing mycobacterial PJI that warrant specialized cultures. Cite this article: Bone Joint J 2022;104-B(1):53–58.

Extensive Assessment of Underlying Etiological Factors in Primary Infertile Men Reduces the Proportion of Men With Idiopathic Infertility

ObjectiveUp to 40% of infertile men remain without a recognized cause (i.e., idiopathic infertility). We aimed to identify, categorize, and report the supposed causes of male infertility in a cohort of white-European men presenting for primary couple’s infertility, by using a thorough and extensive baseline diagnostic work-up.Material and MethodsCross-sectional study of 1,174 primary infertile men who underwent a thorough diagnostic work-up including: detailed medical history, physical examination, hormonal assessment, genetic testing, semen analyses; semen and urine cultures; testis color Duplex US. Men without any identified causal factor were considered as idiopathic. Six different etiological categories were established, and their prevalence was estimated. Logistic regression models estimated the risk of missing causal identification.ResultsA possible causal factor was identified in 928 (81%) men. Hypogonadism was the most frequent identified cause (37%), followed by varicocele (27%). Genetic abnormalities were found in 5% of patients. A causal factor was more easily identifiable for the more severe infertility cases, and azoospermic men were those less likely to be defined as idiopathic (OR and 95% CIs: 0.09; 0.04-0.20). Relative proportion of identified causes remained constant during the 10-year study period (p>0.43).ConclusionsDue to a more comprehensive and extensive diagnostic work-up, at least one underlying cause of male infertility factor in 4 out of 5 infertile men can be identified. Men with a less severe phenotype remain a clinical challenge in terms of establishing a possible etiologic factor. Further studies are needed to assess which subset of infertile men deserves a more extensive work-up.

Cardiac Transthyretin Amyloidosis: Hidden in Plain Sight

Amyloidosis is an underappreciated medical condition with symptoms camouflaging as common medical comorbidities leading to its underdiagnosis due to its systemic involvement. Despite common misconceptions, amyloidosis and its systemic comorbidities are more prevalent and treatable than previously acknowledged by the medical community. There are two major forms of amyloidosis: amyloid light-chain and transthyretin amyloidosis. Each of these have a distinct pathophysiology, diagnostic work-up, treatment, and prognosis. The patient described in this study was diagnosed with transthyretin cardiac amyloidosis months after presenting with heart failure of unknown etiology. Usually, clinicians presume that heart failure results from common comorbidities such as hypertension, diabetes, and hyperlipidemia. Here, the correct etiology was transthyretin cardiac amyloidosis. The patient had five admissions for heart failure symptoms prior to a physician identifying the etiology as cardiac transthyretin amyloidosis. After initiating the transthyretin stabilizer tafamidis, the patient did not experience another heart failure exacerbation. This vignette provides an example of the clinical presentation, diagnostic work-up, and treatment of a patient with cardiac transthyretin amyloidosis. The review of the literature focuses on the epidemiology, and clinical symptoms that should prompt an evaluation for cardiac amyloidosis as well as the diagnostic and therapeutic options are available. Transthyretin cardiac amyloidosis is a rare and underdiagnosed disease, while heart failure is a highly prevalent condition. This clinical vignette seeks to provide education and awareness to an overlooked medical disorder.

533 Uncommon ECG presentation in Tako-tsubo syndrome

Aims We present the case of an 80-year-old woman without prior cardiovascular history, recent instrumental diagnosis of peritoneal carcinomatosis and ongoing oncologic diagnostic work up. Methods and results The patient was admitted to our ED for acute-onset worsening dyspnoea. On first clinical evaluation, she denied typical angina, remarkable clinical features were dyspnoea, tachycardia and hypotension. Admission ECG showed sinus rhythm with posterior and inferior ST elevation (leads DII, aVF, V5, V6) with reciprocal ST segment depression in leads V1–V2. Echocardiography confirmed infero-postero-lateral akinesia determining moderate reduction of LVEF (35–40%), normal aortic root, no pericardial effusion. Laboratory tests revealed normal WBC count, mild anaemia (HB 10.7 g/dl), normal renal function, elevated C-reactive protein (139 mg/l, n.v. < 8). Cardiac troponin I (cTnI) was normal on admission, with significant delta on second determination (0.012 > 2.5 ng/ml, nv < 0.023). ST elevation persisted after BP normalization and hypoxia treatment; so, taken into account the increased procedural risk due to patient’s age and comorbidities, however we decided to perform urgent coronary angiography. Surprisingly, coronary angiography revealed absence of any significant stenosis, with TIMI 3 flow in any coronary segment. The patient was then admitted to the ICU with diagnosis of MINOCA. The next day ECG revealed normalization of ST segment and Q wave in V2–V3. On day 2 new ECG showed new ventricular repolarization abnormalities with T wave inversion in precordial leads. Peak hs-cTnI was >15 000 ng/l. Repeat echocardiography on day 2 reported complete akinesia of all the apical segments of the LV with normo-hyperkinesia of the mid-basal segments (apical ballooning pattern) and severely depressed systolic function (FE 32–35%). During the following days patient’s symptoms improved, with rapid weaning from oxygen therapy and stable haemodynamic parameters. After 10 days the patient repeated echocardiography, which revealed improvement of global LVEF and persisting mild apical hypokinesia, suggesting the diagnostic hypothesis of Tako-Tsubo Syndrome (TTS) or TTS-phenocopy (unfortunately cardiac MRI was not performed). The patient was therefore transferred to oncology department to complete the diagnostic work-up; primary mammary neoplasia was identified, moreover associated with metastasis in the liver and the brain. Unfortunately, the patient died a month later due to non-cardiac causes. This is the case report of an uncommon MINOCA, which presented mimicking inferolateral acute STEMI, but subsequent ECG and echocardiographic evolution showed the more typical TTS pattern, with apical ballooning on echo and deep negative T waves in anterior leads. Conclusions The prevalence of MINOCA is estimated to be 6% to 8% among patients diagnosed with MI, especially women, however it is more common in patients with NSTEMI compared with STEMI; moreover in cases of TTS presenting with ST elevation, usually the elevation is found in anterior leads without reciprocal ST depression; in this patient instead ST elevation was inferolateral with reciprocal anterior ST depression. Absence of obstructive CAD and clinical/echocardiographic evolution allowed us to confirm the diagnosis of MINOCA/TTS.

Indication and outcome of lupus anticoagulant and antiphospholipid antibodies testing in routine clinical practice

Objective Lupus anticoagulant (LAC) and antiphospholipid antibodies (aPL), both further summarized as aPL, are frequently assessed in routine daily clinical practice in diagnostic work-up for suspected autoimmune diseases or to test for underlying risk factors in patients with thrombosis or obstetric complications. The aim of this study is to determine the prevalence of aPL positivity in patients with an indication for aPL testing in routine clinical practice. Methods In this retrospective single center study indication for aPL testing, aPL test results and clinical data were collected for patients tested between June 2015 and April 2018. Results During the study period, 16,847 single aPL tests were performed in 2,139 patients. In 212 patients ≥1 positive aPL test was found, confirmed in 43.9% with a second positive test. Indications for aPL testing were diagnostic work-up/follow-up of autoimmune diseases (33.6%), thrombosis (21.4%) and obstetrical complications (28%). Seventy-four patients (3.5% of all patients) fulfilled the criteria of the antiphospholipid syndrome (APS), of whom 51% were newly diagnosed. Second positive aPL titers and titers of APS patients were significantly higher compared with positive aPL titers at first measurement (p < 0.05). Patients with indication arterial thrombosis and diagnostic work-up/follow-up of autoimmune diseases had significantly higher levels of aCL IgG and anti-β2GPI IgG compared with patients with other indications. Conclusion Prevalence of ≥ 1 positive aPL test was 9.9% and APS was diagnosed in 3.5% of the patients. Patients with arterial thrombosis had significantly higher anti-β2GPI IgG and aCL IgG, which should be confirmed in future studies.

Copeptin; utility in paediatric patients with hyponatraemia

Introduction Copeptin concentrations are a useful component of the diagnostic work-up of paediatric patients with polyuria and polydipsia but the value of measuring copeptin in patients with hyponatraemia is less clear. Case Reports We report 5 children with hyponatraemia in the context of different underlying pathologies. Copeptin concentrations were elevated in 4 cases (13.7, 14.4, 26.1, 233pmol/L; reference range 2.4 – 8.6pmol/L) suggesting that non-osmoregulated vasopressin release (syndrome of inappropriate antidiuretic diuretic hormone or SIADH) was the underlying mechanism for the low sodium levels. In one of the patients there was an underlying diagnosis of Schaaf-Yang syndrome (MAGEL 2 gene mutation) with a clinical picture suggestive of dysregulated vasopressin production with inappropriately high and then low copeptin release. In one hyponatraemic patient, low copeptin concentrations indicated that non-osmoregulated AVP release was not the cause of hyponatraemia and oliguria. Discussion Copeptin measurement did not influence management acutely but helped to clarify the mechanism leading to hyponatraemia when the result was available. Relatively high and low copeptin concentrations in association with hypo and hypernatraemia indicates dysregulated vasopressin production in Schaaf-Yang syndrome. Profound copeptin elevation may be a clue to underlying sepsis.

Pleural Involvement in IgG4-Related Disease: Case Report and Review of the Literature

Diagnostic work-up of IgG4-related disease (IgG4-RD) pleural involvement is a complex task, as there is a broad spectrum of differential diagnoses to consider. We report the case of a patient presenting with relapsing pleural effusion, discussing the main challenges for achievement of a definite diagnosis. A 63-year-old man was admitted for pleural effusion prevalent on the ride side, initially labeled as idiopathic non-specific pleuritis, based on tissue evaluation after a medical thoracoscopy. He was started on steroids with initial improvement, but a later CT scan showed a relapse of pleural effusion associated with diffuse pleural thickening; a subsequent surgical pleural biopsy revealed features suggestive for IgG4-RD, with a marked increase of IgG4 positive plasma cells. High IgG4 serum levels were also found. The present case underlines the importance of increasing awareness of this potential condition among physicians in order to properly guide the diagnostic work-up, as it is likely that IgG4-RD accounts for a proportion of patients with pleural effusions, labeled as idiopathic. In particular, in patients with unexplained pleural effusion, IgG4-RD should be included among differential diagnoses when lymphoplasmacytic infiltration is observed, and a multidisciplinary interaction between clinicians and pathologists appears crucial for an accurate diagnosis and an appropriate management.

Perspective Chapter: Recent Advances in Musculo-Skeletal Ultrasound

Medical imaging specialists continue to explore better ways of demonstrating pathology and anatomy of the musculo-skeletal system. The continuous quest is fuelled by the desire to improve diagnostic yield, perform procedures more quickly and accurately, reduce risks to patient or operator, achieve better cost efficiency and utilize less complex methodologies. In many instances, musculoskeletal ultrasound acts as a screening, diagnostic tool but also guide and monitor therapeutic interventions. The paper outlines the use of ultrasound in the imaging of peripheral nerve disorders, traumatic and atraumatic joint disorders, Doppler techniques such as super micro vascular Imaging and sono-elastography. Refinements in probe technology and application of digital and novel proprietary software, have continued to improve the resolution of ultrasound images and with finer details on a scale not previously possible. With increasing experience and standardization of protocols, Musculoskeletal ultrasound will continue to play a great role in the diagnostic work-up and treatment of related disorders.