The conundrum of neuropsychiatric systemic lupus erythematosus: Current and novel approaches to diagnosis.

Recognising neuropsychiatric involvement by systemic lupus erythematosus (SLE) is of growing importance, however many barriers to this exist at multiple levels of our currently available diagnostic algorithms that may ultimately delay its diagnosis and subsequent treatment. The heterogeneous and non-specific clinical syndromes, serological and cerebrospinal fluid (CSF) markers and neuroimaging findings that often do not mirror disease activity, highlight important research gaps in the diagnosis of neuropsychiatric SLE (NPSLE). Formal neuropsychological assessments or the more accessible screening metrics may also help improve objective recognition of cognitive or mood disorders. Novel serum and CSF markers, including autoantibodies, cytokines and chemokines have also shown increasing utility as part of diagnosis and monitoring, as well as in distinguishing NPSLE from SLE patients without SLE-related neuropsychiatric manifestations. Novel neuroimaging studies also expand upon our existing strategy by quantifying parameters that indicate microarchitectural integrity or provide an assessment of neuronal function. Some of these novel markers have shown associations with specific neuropsychiatric syndromes, suggesting that future research move away from considering NPSLE as a single entity but rather into its individually recognized neuropsychiatric manifestations. Nevertheless, it is likely that a composite panel of these investigations will be needed to better address the gaps impeding recognition of neuropsychiatric involvement by SLE.

Comparison between viral vector and mRNA based COVID-19 vaccination in prevalence and severity of regional immune reactions, and 18F-FDG PET/CT features.

Objectives: The coronavirus pandemic caused by SARS-CoV-2 commenced in late 2019, and global wide vaccination appears to be the only reasonable solution to fight this dreadful virus. There are two main types of COVID-19 immunization using viral vector and mRNA-based vaccines. However, the impact of each of type on 18F-FDG PET/CT needs to be accurately assessed. This study aimed to compare the 18F-FDG PET/CT features of these two types of COVID-19 vaccines. Methods: A total of 188 patients referred for 18F-FDG PET/CT with a recent history of either BioNTech/Pfizer or AstraZeneca COVID-19 vaccination, and a control group of 40 patients with no history of any type of recent vaccination, were included in the study. 18F-FDG PET/CT studies of vaccinated patients assessed for injection site uptake and regional nodal and systemic reactions post vaccination. The data were compared to the control group and to the contralateral side for each patient. The findings were compared between patients who received Pfizer and AstraZeneca vaccines. Results: 18F-FDG PET/CT was semiquantitatively positive in 50.5% of the studied population for vaccine-related features. The ipsilateral axillary and infra- and supraclavicular lymph nodes were significantly larger in size and exhibited higher metabolic activity compared to the contralateral lymph nodes after both types of vaccination. The prevalence of regional nodal reactions post Pfizer and AstraZeneca vaccination was 39% and 17.9% on visual, and 61% and 47.6% on semiquantitative assessments, respectively. Patients receiving the Pfizer vaccine exhibited higher metabolic activity in the ipsilateral regional lymph nodes (p<0.05). No significant difference in the intensity of regional nodal reaction post vaccination was noted between the first four weeks. Conclusion: Significant local and regional nodal reactions are observed after both viral vector and mRNA COVID-19 vaccination with a tendency to extend toward the infra- and supraclavicular nodal stations but not to the pulmonary hilum. The greater intensity and extension of the nodal reaction after Pfizer vaccination suggests a higher possibility of false-positive results on 18F-FDG PET/CT studies using mRNA vaccination technology.

How unmeasured muscle mass affects estimated GFR and diagnostic inaccuracy.

BACKGROUND: Estimated glomerular filtration (eGFR) results based on serum creatinine are frequently inaccurate with differences against measured GFR (mGFR) often attributed to unmeasured non-functional factors, such as muscle mass. METHODS: The influence of muscle mass (measured by dual-energy x-ray absorptiometry, DEXA) on eGFR error (eGFR-mGFR) was evaluated using isotopic mGFR (Tc99m DTPA plasma clearance) in 137 kidney transplant recipients. Serum creatinine was measured by isotopic-calibrated enzymatic analysis, converted to eGFR using Chronic Kidney Disease EPIdemiology (CKD-EPI) formula, then unindexed from body surface area. FINDINGS: Unindexed CKD-EPI eGFR error displayed absent fixed bias but modest proportional bias against reference mGFR. eGFR error correlated with total lean mass by DEXA (r=-0·350, P<0·001) and appendicular skeletal muscle index (ASMI), a proxy for muscularity (r=-0·420, P<0·001). eGFR was falsely reduced by -5·9 ± 1·4 mls/min per 10 kg lean mass. Adipose mass and percentage fat had no effect on error. Muscle-associated error varied with each eGFR formula and influenced all CKD stages. Systemic eGFR error was predicted by ASMI, mGFR, recipient age, and trimethoprim use using multivariable regression. Residual plots demonstrated heteroscedasticity and greater imprecision at higher mGFR levels (P<0·001), from increased variance corresponding to higher absolute values and unreliable prediction by serum creatinine of high mGFR. Serum creatinine correlated with ASMI independent of mGFR level (r = 0·416, P<0·001). The diagnostic test performance of CKD-EPI eGFR to predict CKD stage 3 (by mGFR) was weakest in cachexia (sensitivity 68·4%) and muscularity (specificity 47·4%, positive predictive value 54·5% for the highest ASMI quartile). INTERPRETATION: Serum creatinine and eGFR are imperfect estimates of true renal function, with systemic errors from muscle mass, tubular secretion, and intrinsic proportional bias; and additional inaccuracy at the extremes of renal function and patient muscularity. Cautious interpretation of eGFR results in the context of body habitus and clinical condition is recommended.

Positional ischaemia of transplant kidney: A rare cause of early graft dysfunction.

Kinking of the kidney transplant vessels late after the operation is a rare complication that can lead to significant morbidity and mortality. We present a case of positional ischemia of the renal allograft resulting from dynamic and positional kinking of the graft vasculature, which was diagnosed by ultrasonography with the patient standing. The graft was repositioned into the sub-rectus pocket and the ischaemic injury resolved.

Multicentre, randomised, blinded, control trial of drug-eluting balloon vs Sham in recurrent native dialysis fistula stenoses.

BACKGROUND: Endovascular treatment of autogenous arteriovenous haemodialysis fistula stenosis has high reintervention rates. We investigate the effect of drug-eluting balloons in the treatment of recurrent haemodialysis fistula stenosis. METHODS: This is a randomised, controlled, investigator-initiated and run, prospective, blinded, multicentre trial. Patients with recurrent autogenous arteriovenous haemodialysis fistula stenosis received standard endovascular treatment plus drug-eluting balloon or standard endovascular treatment plus uncoated balloon (Sham). Primary endpoint was late lumen loss in trial area on ultrasound at 6 weeks, 3, 6 and 12 months. Secondary endpoints were freedom from reintervention to the Index Trial Area and decline in fistula flow (Qa). Interim analysis was performed at 6 months (unblinded due to timeliness). RESULTS: Patients with 132 recurrent stenoses (48% in bare Nitinol stents) were randomised with 70 receiving drug-eluting balloon and 62 Sham. At 6 months, decline in late lumen loss was 0.23 ± 0.03 mm/month for Sham and 0.045 ± 0.03 mm/month for drug-eluting balloon arm, a significant difference (0.18 mm, p = 0.0002). At 12 months, this difference persisted at 0.12 mm (p = 0.0003). At 6 months, significant difference in late lumen loss for instent restenoses (p = 0.0004) was observed, with non-significant difference for unstented restenoses (p = 0.065). Mean time for freedom from reintervention was 10.14 months for Sham versus 42.39 months for drug-eluting balloon (p = 0.001). The same was shown for instent (p = 0.014) and unstented (p = 0.029) restenoses. Qa decline rate at 6 months was 36.89 mL/min/month (Sham) and 0.41 mL/min (drug-eluting balloon). The difference was significant (36.48 mL/min; p = 0.02) and persisted to 12 months (p = 0.44). CONCLUSION: Paclitaxel drug-eluting balloon significantly delays restenosis after angioplasty for recurrent autogenous arteriovenous haemodialysis fistula stenosis, persisting to 12 months. Drug-eluting balloon significantly increases freedom from reintervention at 12 months with these effects true in stented and unstented fistulas.

Intravascular metastatic melanoma: a difficult diagnosis.

Melanoma is a common cancer with the potential for widespread metastasis; however intravascular metastasis is extremely rare. We report an unusual case of a patient with metastatic melanoma in whom (18) F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) demonstrated an intravascular melanoma metastasis in the superior vena cava (SVC), successfully treated with external beam radiotherapy. To our knowledge, this is the first reported case where FDG PET-CT was used to make this diagnosis.

Defining a significant stenosis in an autologous radio-cephalic arteriovenous fistula for hemodialysis.

The current definition of a significant stenosis in an autologous arteriovenous fistula (aAVF), the percentage narrowing compared with the adjacent "normal" vessel, is inaccurate. We believe a significant stenosis in the aAVF is an absolute minimal luminal diameter determined by the requirements of the hemodialysis pump. To determine what absolute diameter constitutes a hemodynamically significant stenosis in a radio-cephalic autologous arteriovenous fistula (RC aAVF), the minimal luminal diameter of dysfunctional RC aAVF was compared to that of functional RC aAVF using grayscale and color ultrasound. There were 93 fistulas in study group and 77 in control group. The mean minimum luminal diameter in study group was significantly lower than in control group (2.19 vs. 4.71 mm, p 0.001). With a cutoff value of 2.7 mm, there was 90% sensitivity and 80% specificity in distinguishing functional fistula from dysfunctional fistula. The area under the receiver-operator curve was 90% (CI 84-94%), indicating that a 2.7 mm diameter is accurate in discriminating functional from dysfunctional fistulas. An absolute minimal luminal diameter of 2.7 mm, as determined with grayscale and color ultrasound, is a useful cutoff for defining significant stenosis in a RC aAVF.

Colour duplex ultrasound accurately identifies focal stenoses in dysfunctional autogenous arteriovenous fistulae.

AIMS: The aims of this study is to correlate colour duplex ultrasonography (US) with contrast fistulography for the detection of functional stenoses in the autogenous AVF (arterio-venous fistula) circuit. METHODOLOGY: Colour duplex US scans of 93 dialysis patients with dysfunctional AVF were compared with fistulograms performed within 6 weeks of the US. The AVF circuit was divided into six zones: inflow artery; anastomosis; distal vein; mid vein; proximal vein; and central vein. Colour duplex US and fistulogram images/reports were independently re-reported for stenoses in each fistula zone by two trained clinicians blinded to the outcomes. For each fistula, only zones examined by both modalities were included in the study. Kappa analysis of the results was performed to assess the accuracy of colour duplex US in the dysfunctional AVF circuit. RESULTS: Most AVF studied were radio-cephalic (59%) or brachio-cephalic (22%). Stenoses identified within the AV circuit in order of frequency were: distal vein (41), mid vein (23), arterial (12), proximal vein (7) and anastomosis (3). The interval between US and fistulogram studies was 33 + or - 29 days. Congruence of results between US and fistulograms ranged from 85% to 96%, depending on the zone examined. Kappa analysis of this US versus fistulogram data was also moderate to good, ranging from 0.72 and 0.91. CONCLUSIONS: Colour duplex US provides an accurate diagnostic assessment of a dysfunctional autogneous AVF, and is an important planning tool for subsequent open or endovascular intervention. It is particularly accurate in the peri-anastomotic area of the fistula which harbours the majority of fistula problems.

Ventilation-perfusion mismatch resulting from iatrogenic pulmonary vein stenosis after radiofrequency ablation: a case report.

A lobar ventilation-perfusion mismatch is reported in a patient with right superior pulmonary vein stenosis, developing after radiofrequency ablation for atrial fibrillation. Radionuclide lung perfusion tomography was performed to assist with clinical management. Serial planar lung scintigraphy demonstrated no improvement in the perfusion abnormality despite interventional stenting. Iatrogenic pulmonary vein stenosis may potentially mimic pulmonary embolic disease.

Doppler sonography in the diagnosis of round ligament varicosities during pregnancy.

Round ligament varicosities during pregnancy are an important differential diagnosis of complicated inguinal hernias and have been reported only rarely. Diagnosis is reassuring and may prevent unnecessary surgical exploration. We describe a case of round ligament varicosities presenting during pregnancy that was readily diagnosed with Doppler sonography.

Sonographic appearance of a postpartum pyomyoma with gas production.

Pyomyoma or suppurative leiomyoma is a potentially fatal complication of uterine leiomyomas. It is a rare condition with only a small number of reported cases since the era of antibiotics, and the descriptions of its sonographic appearance has been limited. We present a case of a pyomyoma associated with gas production, including a brief review of the reported sonographic features.

Neonatal fungal ventriculitis.

Intracranial fungal infection is increasingly seen in the neonatal intensive care setting, with premature infants at greatest risk. We report a case of fungal ventriculitis in an extremely low birth weight neonate due to Candida species. Cranial sonographic examination revealed extensive ventricular stranding with complete resolution in response to therapy.

Oral cyclosporine but not tacrolimus reduces renal transplant blood flow.

BACKGROUND: Calcineurin inhibitors are important immunosuppressive agents, but cause nephrotoxicity. METHODS: Instantaneous intra-renal transplant hemodynamics were assessed in 22 patients using quantitative cineloop color Doppler imaging after dosing with microemulsion cyclosporine (CSA) or tacrolimus (TAC). RESULTS: CSA dosing resulted in renal hypoperfusion, with a mean relative reduction of 43%+/-20% (range 22-76%) in maximal fractional area (MFA) of color pixels to nadir, compared to baseline. The mean effect occurred 1.1+/-0.9 hr (median 1 hr) after CSA dosing and was abrogated by calcium channel blockers (P <0.05). The main renal artery velocities, resistive index and small vessel perfusion were unchanged, suggestive of medium-sized arteries mediated vasoconstriction. In contrast, TAC did not alter renal vascularity (2.3+/-4.0% absolute reduction of MFA color pixels vs. 10.7+/-6.5% with CSA, P <0.01). CONCLUSION: CSA, but not TAC, induces phasic hypoperfusion of variable severity within small to medium sized intra-renal arteries soon after dosing, mitigated by calcium channel blockade.

Detection of chronic allograft nephropathy by quantitative doppler imaging.

BACKGROUND: Chronic allograft nephropathy (CAN) is the major cause of graft loss, and early detection is desirable to avoid irreversible graft damage. We have evaluated a new technique of color Doppler quantification using Cineloop (Philips Medical Systems, Bothell, WA) imaging for noninvasive diagnosis of CAN. METHODS: Provisional normal ranges were defined by pilot study (n=13) and prospectively tested in stable recipients in whom CAN was independently quantified by contemporaneous histology (n=67), using the Banff schema. RESULTS: The maximal fractional area (MFA, systolic color pixels/total area) was 28.7+/-9.7% in normal subjects and reduced to 18.8+/-8.0% in grade 1 and 12.5+/-6.4% in grade 2 CAN (both P<0.001). The minimum color fractional area was reduced from 10.3+/-5.3% in normal subjects to 3.1+/-2.6% in grade 2 CAN (P<0.001), but was less useful. Distance from peripheral color pixels to capsule increased in CAN grade 2 versus 0 (6.0+/-1.6 vs. 3.9+/-1.0 mm, respectively; P<0.001). Calcineurin inhibitor nephrotoxicity reduced MFA (18.0+/-9.3 vs. 26.9+/-10.7%; P<0.001) and other dynamic measurements. Parenchymal damage exerted minimal effect on resistance index, mean variance, and peak Doppler velocity. MFA (cutoff<17.3%) can diagnose CAN (sensitivity 69%, specificity 88%, positive predictive value 86%) and severe CAN (sensitivity 87%, specificity 71%, negative predictive value 95%). Distance to capsule >5 mm was less sensitive (49%) but more specific (91% alone, and 97% combined with MFA). CONCLUSIONS: In conclusion, quantitative Doppler ultrasound can reliably detect CAN and, although imperfect at correctly grading, allows recognition of significant tubulointerstitial damage for initiation of a confirmatory needle core biopsy.

Technique of color Doppler quantification of vascularity in transplanted kidneys.

A new technique for the quantification of vascularity based on the analysis of color Doppler images is described. We utilized velocity information obtained directly from cineloops transferred to a computer for off-line analysis. This methodology was used in transplanted kidneys to assess parenchymal vascularity on the basis of percentage color pixel density and mean flow velocity in mid-kidney cross-sectional regions of interest and the distance from the most peripheral color pixels to the capsule of the kidney. Other color Doppler quantitative methods have lacked reproducibility, and therefore before evaluation of the clinical usefulness of this technique, intraobserver reproducibility and interobserver reliability were assessed in 42 patients; no statistically significant variation was demonstrated. In 13 patients with normally functioning transplants, the mean maximum color pixel density was 34.7+/-13.4%, the mean flow velocity was 5.2+/-0.9 cm/second, and the mean distance to the capsule was 3.3+/-1.1 mm.