Table Info

Table 2.

Description of study procedures

Procedure	Description
Physical examination	Includes the Tinel sign at the wrist, Phalen test, and sensory disturbance detected over the median nerve-innervated area.
Laboratory tests	Includes blood tests of antinuclear antibodies, rheumatoid factor and troponin I to exclude rheumatic disease.
Electromyography	The electrical testing of median nerve function can detect the presence, location, and extent of CTS, and help to determine the most effective treatment.
Electrocardiogram	The ECG will be analyzed for rhythm, presence of previous pseudoinfarction, conduction abnormalities and QRS amplitudes, including left ventricular hypertrophy and low voltage.
Wrist ultrasound (only in symptomatic CTS)	The ultrasound of the wrist will be done by the rheumatologist and will be used to measure the transversal area of the median nerve and confirm the absence of lesion space occupying or anatomical abnormalities.
Whole-body, cardiac and wrists/hands scintigraphy with ^99mTc-DPD	It will be performed to detect amyloid deposits. Before surgery, patients (cases and controls) will undergo a scintigraphy with ^99mTc-DPD, obtaining whole-body scans; acquisition of images of vascular, blood-pool and late phases of the radiopharmaceutical’s distribution in the hands and wrists; cardiac images synchronized with cardiac rhythm and acquired with low-dose CT scan (total amount of radiation of 6.3 mSv); cardiac disease will be characterized according to the semiquantitative Perugini categories: grade 0: no cardiac uptake and normal rib uptake; grade 1: cardiac uptake which is less than rib uptake; grade 2: cardiac uptake with intensity similar to rib uptake; grade 3: cardiac uptake greater than rib uptake with mild or absent rib uptake. Cardiac SPECT/CT imaging acquired at 2 hours and whole-body at 2h30 after injection.
Synovial biopsy (Congo red)	Tenosynovial tissues obtained during surgery (cases and controls) will be analyzed using Congo red. Histopathological analysis will be conducted when necessary. The degree of amyloidosis will be divided into 3 categories and evaluated semiquantitatively: grade I, II, III representing mild, moderate and severe amyloid deposition, respectively.
Mass spectrometry analysis	If the Congo red stain is positive, mass spectrometry will be performed to differentiate and identify the type of amyloid protein.
Genetics tests	If the Congo red stain is positive, genetic test will be carried out to detect TTR gene mutations.

CT: computed tomography; CTS: carpal tunnel syndrome; ECG: electrocardiogram; TTR: transthyretin; ^99mTc-DPD: ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid

Declarations

Author contributions

SP and AM: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. MC, BSP and ASP: Conceptualization. JS and IF: Writing—review & editing. PM, PN, JP and LC: Conceptualization. EM: Validation, Writing—original draft, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study protocol was approved by the Ethics Committee for Health of Centro Hospitalar Universitário de São João, reference No: CE 200/2020, and complied with the principles of the Helsinki Declaration.

Consent to participate

Informed consent to participate in the study was obtained from all participants.

Consent to publication

Not applicable.

Availability of data and materials

The raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.

Funding

This study is supported by a research grant from Pfizer Grant [59852013]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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