Transthyretin amyloid polyneuropathy in France: A cross-sectional study with 413 patients and real-world tafamidis meglumine use (2009-2019).

OBJECTIVE: We aimed to describe characteristics of patients with ATTR variant polyneuropathy (ATTRv-PN) and ATTRv-mixed and assess the real-world use and safety profile of tafamidis meglumine 20mg. METHODS: Thirty-eight French hospitals were invited. Patient files were reviewed to identify clinical manifestations, diagnostic methods, and treatment compliance. RESULTS: Four hundred and thirteen patients (296 ATTRv-PN, 117 ATTRv-mixed) were analyzed. Patients were predominantly male (68.0%) with a mean age of 57.2±17.2 years. Interval between first symptom(s) and diagnosis was 3.4±4.3 years. First symptoms included sensory complaints (85.9%), dysautonomia (38.5%), motor deficits (26.4%), carpal tunnel syndrome (31.5%), shortness of breath (13.3%), and unexplained weight loss (16.0%). Mini-invasive accessory salivary gland or punch skin and nerve biopsies were most common, with a performance of 78.8-100%. TTR genetic sequencing, performed in all patients, revealed 31 TTR variants. Tafamidis meglumine was initiated in 156/214 (72.9%) ATTRv-PN patients at an early disease stage. Median treatment duration was 6.00 years in ATTRv-PN and 3.42 years in ATTRv-mixed patients. Tafamidis was well tolerated, with 20 adverse events likely related to study drug among the 336 patients. CONCLUSION: In France, ATTRv patients are usually identified early thanks to the national network and the help of diagnosis combining genetic testing and mini-invasive biopsies.

3D deep convolutional neural network segmentation model for precipitate and porosity identification in synchrotron X-ray tomograms.

New developments at synchrotron beamlines and the ongoing upgrades of synchrotron facilities allow the possibility to study complex structures with a much better spatial and temporal resolution than ever before. However, the downside is that the data collected are also significantly larger (more than several terabytes) than ever before, and post-processing and analyzing these data is very challenging to perform manually. This issue can be solved by employing automated methods such as machine learning, which show significantly improved performance in data processing and image segmentation than manual methods. In this work, a 3D U-net deep convolutional neural network (DCNN) model with four layers and base-8 characteristic features has been developed to segment precipitates and porosities in synchrotron transmission X-ray micrograms. Transmission X-ray microscopy experiments were conducted on micropillars prepared from additively manufactured 316L steel to evaluate precipitate information. After training the 3D U-net DCNN model, it was used on unseen data and the prediction was compared with manual segmentation. A good agreement was found between both segmentations. An ablation study was performed and revealed that the proposed model showed better statistics than other models with lower numbers of layers and/or characteristic features. The proposed model is able to segment several hundreds of gigabytes of data in a few minutes and could be applied to other materials and tomography techniques. The code and the fitted weights are made available with this paper for any interested researcher to use for their needs (https://github.com/manasvupadhyay/erc-gamma-3D-DCNN).

A cadaveric anatomical study of the adrenals: Relationship with the posterior abdominal wall muscles revisited.

AIM OF THE STUDY: The main difficulties during retroperitoneal laparoscopic adrenalectomies are due to its location. Our objective was to define the relationship of the adrenals with the diaphragm and the psoas muscle. METHODS: Our work is an anatomical dissection of 80 fresh cadavers' adrenals. To study the right adrenal, we performed a right nephrectomy and adrenal remained attached to the Inferior vena cava by its main vein. On the left, the edges of the adrenal have been identified by needles and the adrenal was reclined to study its projection on the posterior muscular wall. RESULTS: The right adrenal is located higher, 13mm [4-20mm] above the medial arcuate ligament (MAL) in 16 cases (40%). Its lower border was at the same level as the MAL in 18 cases (45%) and 11mm [10-17mm] below the MAL in 6 cases (15%). The posterior support of the right adrenal was the right crus of the diaphragm (Right-CD) in 34 cases (85%) and straddling the Right-CD and the psoas in 6 cases (15%). The study of the relationships of the left adrenal with the MAL showed that the lower edge of the gland was at its same level in 16 cases (40%) and below in 24 cases (60%) by 14mm [8-24mm]. The posterior support of the left adrenal was the left crus of the diaphragm (Left-CD) in 16 cases (40%) and straddling the Left-CD and the psoas in 24 cases (60%). CONCLUSIONS: Our results showed that the right adrenal is higher. The MAL is an important posterior element to the adrenal gland that could serve as an anatomical landmark to identify the adrenal during laparoscopic adrenalectomy.

Vesico-vaginal fistula in Tunisia: Epidemiology and risk factors of treatment failure.

INTRODUCTION: Vesico-vaginal fistula (VVF) is a global healthcare problem that has a high prevalence in developing countries. The aim of this work is to study the epidemiological, clinical and therapeutic characteristics of VVF post-obstetric and gynecologic procedures in order to identify the predictive factors of surgical treatment failure. METHODS: Data were collected from 132 VVF patients in our institution between 1985 and 2017. VVF was classified according to Zmerli's classification. Patients underwent surgical treatment and were evaluated after a follow-up period of 6 months. Successful treatment was defined as the absence of urine leakage whereas recurrence was defined as the presence of urine leakage immediately after the surgery or after a period of dryness with a confirmed VVF. Risk factors of surgical treatment failure were identified. RESULTS: The average age of patients was 44 years. The patients were multiparous in 62% of cases. VVF was consecutive to hysterectomy in 62.1% of cases, and after childbirth in 34%. VVF was retro-trigonal in 99 cases (75%) and trigonal in 33 cases (25%). The average size of the fistula was 1cm (0.3-2cm). VVF repair was performed by vaginal approach in 68% of cases and abdominal approach in 32% of cases. Treatment failure was noted in 36 patients (27%). Predictive factors of treatment failure were: vaginal fibrosis (P<0.001); trigonal location of the fistula (P<0.001); large diameter of the VVF>1cm (P<0.001); and complex and complicated fistulas (P=0.02). CONCLUSION: Although Tunisia is a developing country, the main cause of VVF was not obstetrical. Treatment failure, noted in almost one third of cases, was, in our series, correlated with the quality of the vaginal tissue, the size and the location of the fistula, and its complexity. LEVEL OF PROOF: 4.

Upper limb onset of hereditary transthyretin amyloidosis is common in non-endemic areas.

BACKGROUND AND PURPOSE: The aim is to describe an uncommon phenotype of hereditary ATTR neuropathy with upper limb onset. METHODS: The French TTR Familial Amyloid Polyneuropathy database was used for a retrospective evaluation of 32 consecutive patients with upper limb onset of the neuropathy (study group) and they were compared to 31 Portuguese early-onset patients and 99 late-onset patients without upper limb onset. RESULTS: Initial upper limb symptoms were mostly sensory. Lower limb symptoms began 2.3 ± 3 years after upper limb symptoms. Twenty-four (75%) patients were initially misdiagnosed, with 15 different diagnoses. More patients in the study group had a Neuropathy Impairment Score upper limb/lower limb ratio > 1 compared to the late-onset patient group. The study group had significantly more pronounced axonal loss in the median and ulnar motor nerves and the ulnar sensory and sural nerves. On radial nerve biopsies (n = 11), epineurial vessels were abnormal in six cases, including amyloid deposits in vessel walls (3/11), with vessel occlusion in two cases. CONCLUSION: Upper limb onset of hereditary ATTR neuropathy is not rare in non-endemic areas. It is important to propose early TTR sequencing of patients with idiopathic upper limb neuropathies, as specific management and treatment are required.

Retro-peritoneal paraganglioma, diagnosis and management.

INTRODUCTION: Paragangliomas, defined as extra-adrenal chromaffin-cells tumors, are rarely located in the retro-peritoneum. Clinical presentation is similar to pheochromocytoma, and mainly depends on the producing character of the tumor. Positive diagnosis requires plasmatic and urinary hormonal assays. Radiological and isotopic explorations are essential before surgery. The only curative therapeutic strategy is surgical, associated to peri-operative prevention and monitoring of the frequently reported hemodynamic and cardiovascular disorders. Outcome depends of the metastatic character of the tumor, the presence of tumor remnant after surgical resection. Genetic study is recommended; the risk of recurrence and association to other neoplasm is more described in genetic forms. MATERIAL AND METHODS: Authors report 5cases of retro-peritoneal paraganglioma, operated in the department of urology of Hospital, between 2013 and 2017. Observations are about 2men and 3women. Clinical presentation is not always specific and paraganglioma may be discovered fortuitously. Two patients have been operated by coelioscopic approach, midline incision was performed in two other cases, and dorsal lumbotomy associated to a Rutherford-Morrison incision in a patient. RESULTS: Two patients presented resistant hypertension and palpitation associated to suspect retro-peritoneal masses in imagery and elevated urinary methoxylated derivates before surgery. One patient was asymptomatic and the tumor was discovered in imagery. Per-operative hypertensive crisis and sinus tachycardia occurred in a case. The average follow-up period is 22.8months. Hypertension and palpitation disappeared after surgery. There was no recurrence for all the operated patients. CONCLUSION: Retro-peritoneal paraganglioma is a rare condition. Symptoms are not specific and clinical presentation may be similar to pheochromocytoma. Abdominal CT-scan and MRI, in association with MIBG scintigraphy are strongly evocative. Histological examination ensures diagnosis. Per-operative cardio-vascular disorders are to consider and must prevented and managed by anesthesiologists. Complete surgical resection is the only curative treatment and avoids recurrences.

Multimodality Imaging of Cardiac Transthyretin Amyloidosis 16 Years After a Domino Liver Transplantation.

We report the case of a 62-year-old man hospitalized in May 2015 for symptomatic heart failure. His medical history included two liver transplantations. The first liver transplantation was performed in 1999 for a mixed alcoholic and hepatitis C-related cirrhosis and the patient received the liver of another patient with Val30Met transthyretin amyloidosis using the domino technique. In 2008, he complained of neuropathic pains and an iatrogenic-acquired transthyretin amyloidosis was diagnosed. On cardiac evaluation, amyloidosis was suspected. In March 2010, a second liver transplantation was performed with a deceased donor without complication. In May 2015, a first episode of symptomatic heart failure occurred and cardiac amyloidosis was investigated by a multimodality evaluation. Electrocardiogram, cardiac biomarkers, echocardiography, and cardiac MRI were in favor of the diagnosis of amyloidosis, whereas 99m Tc-dicarboxypropane diphosphonate scintigraphy was not. Endomyocardial biopsy finally confirmed the positive diagnosis of iatrogenic-acquired cardiac amyloidosis. This case is, to the best of our knowledge, the first to report biopsy-proven cardiac amyloidosis induced by domino liver transplantation and progressing heart failure in spite of retransplantation. The diagnostic modalities are discussed. This case should alert physicians to the cardiac risk in domino liver transplanted patients.

Microsolvation of NO(+) in Ar(n) clusters: A theoretical treatment.

At present, we investigate the structure and the stability of NO(+)Arn (n ≤ 54) ionic clusters using analytical potential functions. The energy of these systems is described using additive potentials with VNO(+)Ar and VAr-Ar representing the pair potential interactions. To find the geometry of the lowest energy isomers of the NO(+)Arn clusters, we use the so-called basin hopping method of Wales et al. which combines a Monte-Carlo exploration and deformation method. The reliability of our model was checked by deriving the structures of the NO(+)Arn systems (n = 1, 2, 3 and 4) using ab initio Moller-Plesset perturbation theory up to second order (MP2) in connection with the aug-cc-pVTZ basis set. Magic numbers for sizes n = 8, 12, 18, 22, and 25 are found and they show a high relative stability. Our results reveal that a transition in the NO(+) ion coordination from 8 (square antiprism) to 12 (icosahedrons) occurs for n = 11. Examination of the stable structures of the ionic clusters demonstrates that the first solvation shell closes at n = 12. Furthermore, we found that the NO(+)Arn (n = 12-54) clusters are structurally very similar to the homogenous rare gas clusters with a polyicosahedral packing pattern. The distribution exhibits an additional magic number at n = 54, consistent with the completion of a second solvation sphere around NO(+). The effects of microsolvation of NO(+) cation in Ar clusters are also discussed. Generally, our results agree with the available experimental and theoretical findings on NO(+)Arn clusters and more generally on diatomics solvated in Ar clusters.

Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study.

BACKGROUND: Respiratory variation in pulse pressure (ΔPP) is commonly used to predict the fluid responsiveness of critically ill patients. However, some researchers have demonstrated that this measurement has several limitations. The present study was designed to evaluate the proportion of patients satisfying criteria for valid application of ΔPP at a given time-point. METHODS: A 1 day, prospective, observational, point-prevalence study was performed in 26 French intensive care units (ICUs). All patients hospitalized in the ICUs on the day of the study were included. The ΔPP validity criteria were recorded prospectively and defined as follows: (i) mechanical ventilation in the absence of spontaneous respiration; (ii) regular cardiac rhythm; (iii) tidal volume ≥8 ml kg(-1) of ideal body weight; (iv) a heart rate/respiratory rate ratio >3.6; (v) total respiratory system compliance ≥30 ml cm H2O(-1); and (vi) tricuspid annular peak systolic velocity ≥0.15 m s(-1). RESULTS: The study included 311 patients with a Simplified Acute Physiology Score II of 41 (39-43). Overall, only six (2%) patients satisfied all validity criteria. Of the 170 patients with an arterial line in place, only five (3%) satisfied the validity criteria. During the 24 h preceding the study time-point, fluid responsiveness was assessed for 79 patients. ΔPP had been used to assess fluid responsiveness in 15 of these cases (19%). CONCLUSIONS: A very low percentage of patients satisfied all criteria for valid use of ΔPP in the evaluation of fluid responsiveness. Physicians must consider limitations to the validity of ΔPP before using this variable.

Antimicrobial prophylaxis protocol based on rectal swab culture before prostate biopsy to prevent infectious complications: a prospective randomized comparative study.

PURPOSE: To evaluate the benefit of targeted antibiotic prophylaxis (TAP) based on rectal swab culture in comparison with standard empiric antimicrobial prophylaxis in patients undergoing transrectal ultrasound-guided needle biopsy of the prostate (TRUS-BP), as well as to assess rate of fecal carriage of Fluoroquinolone-resistant Enterobacterales FQRE. PATIENTS AND METHODS: We prospectively analyzed data that randomized 157 patients within two groups: (G1) TAP according to rectal swab performed 10 days before PB; (G2): empirical antibiotic prophylaxis with ciprofloxacin. Prevalence of FQRE digestive carriage and risk factors were investigated. Incidence of infectious complications after (TRUS-BP) in each group was compared. RESULTS: G2 included 80 patients versus 77 in G1. There was no difference between the two groups regarding age, diabetes, prostate volume, PSA, number of biopsy cores, and risk factors for FQRE. In G2, the prevalence of FQRE digestive carriage was 56.3% all related to E. coli species. In the case of digestive carriage of FQRE, TAP according to the rectal swab culture with third-generation cephalosporins was performed in 73.3%. Patients with FQRE had history of FQ use within the last 6 months in 17.8% (p = 0.03). Rate of febrile urinary tract infection after PB was 13% in G1 and 3.8% in G2 (p = 0.02). CONCLUSIONS: Incidence of FQ resistance in the intestinal flora of our local population was prevalent. Risk factor for resistance was the use of FQ within the last 6 months. TAP adapted to rectal swab, mainly with third-generation cephalosporins, significantly reduced the rate of infectious complications after (TRUS-BP).

Reversibility of acquired amyloid polyneuropathy after liver retransplantation.

Domino liver transplantation (DLT) has become an accepted procedure designed to address problems with organ limited supply. However, cases of acquired amyloid neuropathy are increasingly being recognized following this procedure. Until now, only one patient had undergone liver retransplantation and follow-up findings were not reported. We describe the case of a 72-year-old patient with partial recovery from acquired amyloid neuropathy following retransplantation with a deceased donor 7 years after DLT performed for end-stage liver disease. His clinical and paraclinical improvement is described, and the impact of this case on the indication for a domino procedure and the challenges linked to retransplantation are discussed.

[Ileocolic intussusception from metastatic renal cell carcinoma]. / Localisation iléale d'un carcinome à cellules rénales révélée par une invagination iléo-cæcale.

The lung, the liver, the bone tissue and the brain are the most frequent sites for renal cell carcinoma metastasis. Small bowel metastasis from renal cell carcinoma is rare, with only few cases published. We report the case of ileal metastasis from operated kidney cancer revealed by ileocolic intussusception and causing intestinal obstruction in a 32-year-old woman.

Non-thermal plasma disinfecting procedure is harmless to delicate items of everyday use.

Non-thermal plasma (NTP) is a well-known decontamination tool applicable for a wide range of microorganisms and viruses. Since the recent COVID-19 pandemic highlighted the need to decontaminate all daily used items, it is highly desirable to address the applicability of NTP, including its possible harmful effects. To the best of our knowledge, a comprehensive characterization of NTP effects on sensitive materials is still lacking. We investigated the potential damage to common materials of daily use inflicted by air atmospheric NTP generated in Plasmatico v1.0. The materials tested were paper, various metals, and passive and active electronic components modelling sensitive parts of commonly used small electronic devices. The NTP-exposed paper remained fully usable with only slight changes in its properties, such as whitening, pH change, and degree of polymerization. NTP caused mild oxidation of copper, tinned copper, brass, and a very mild oxidation of stainless steel. However, these changes do not affect the normal functionality of these materials. No significant changes were observed for passive electronic components; active components displayed a very slight shift of the measured values observed for the humidity sensor. In conclusion, NTP can be considered a gentle tool suitable for decontamination of various sensitive materials.

Squamous and glandular metaplasia related to a renal pelvis stone leading to secondary pyeloureteral junction syndrome.

Keratinizing squamous metaplasia of the renal pelvis is a rare lesion of the upper urinary tract that can occur in the context of chronic aggression to the urothelium, potentially leading to a secondary pyeloureteral junction syndrome. We report the case of a 43-year-old patient discovered intraoperatively in relation to a renal pelvis stone causing a pyeloureteral junction syndrome. The extemporaneous histological examination ruled out a malignant process, and we performed a pyeloplasty according to KUSS-ANDERSON technique. This pathology should be recognized by the urologist for appropriate management. Treatment is conservative, with extended follow-up to detect recurrences or carcinomatous degenerations.

Paratesticular leiomyoma: A case report of a rare entity.

Paratesticular leiomyoma is an extremely rare benign tumour. It is often asymptomatic. It is sometimes difficult to distinguish leiomyomas from malignant testicular tumours, which leads to radical orchidectomy, despite its benign nature. Magnetic resonance imaging can be helpful to make conservative management of this lesion.

Prostate adenocarcinoma metastasis to the testis: A new case report.

Prostate cancer (PCa) in the second most common cancer in men worldwide. It commonly metastasizes to the bone, lymph nodes, liver and lungs. Synchronous or metachronous testicular metastasis is a rare finding, generally diagnosed incidentally after bilateral orchidectomy for hormonal management in patients with advanced PCa, or at autopsy. We report a case of a 55-year-old male, presenting a PCa and who developed a single testicular metastasis treated by radical orchidectomy, while he was under hormonotherapy.

The onset of left ventricular diastolic dysfunction in SHR rats is not related to hypertrophy or hypertension.

Left ventricular (LV) diastolic dysfunction, particularly relaxation abnormalities, are known to be associated with the development of LV hypertrophy (LVH). Preliminary human and animal studies suggested that early LV diastolic dysfunction may be revealed independently of LVH. However, whether LV diastolic dysfunction is compromised before the onset of hypertension and LVH remains unknown. We therefore evaluated LV diastolic function in spontaneously hypertensive rats (SHR) at different ages and tested whether LV diastolic dysfunction is associated with abnormal intracellular calcium homeostasis. LV systolic and diastolic functions were evaluated by invasive and echocardiographic methods in 3-week-old (without hypertension) and 5-week-old (with hypertension) SHR and Wistar-Kyoto control rats. Basal intracytoplasmic calcium and sarcoplasmic reticulum (SR) Ca(2+) contents were measured in cardiomyocytes using fura-2 AM. Sarco(endo)plasmic Ca(2+)-ATPase isoform 2a (SERCA 2a) and phospholamban (PLB) expressions were quantified by Western blot and quantitative RT-PCR techniques. LV relaxation dysfunction was observed in 3-week-old SHR rats before onset of hypertension and LVH. An increase in basal intracytoplasmic Ca(2+) and a decrease in SR Ca(2+) release were demonstrated in SHR. Decreased expression of SERCA 2a and Ser16 PLB (p16-PLB) protein levels was also observed in SHR rats, whereas mRNA expression was not decreased. For the first time, we have shown that LV myocardial dysfunction precedes hypertension in 3-week-old SHR rats. This LV myocardial dysfunction was associated with high diastolic [Ca(2+)](i) possibly due to decreased SERCA 2a and p16-PLB protein levels. Diastolic dysfunction may be a potential predictive marker of arterial hypertension in genetic hypertension syndromes.

Effect of intra-abdominal hypertension on left ventricular relaxation: a preliminary animal study.

BACKGROUND: In the intensive care unit, intra-abdominal hypertension (IAH) is a frequently encountered, life-threatening condition. The aim of this animal study was to evaluate the effect of IAH on left ventricular (LV) relaxation (i.e. the active phase of diastole). METHODS: Seven male rabbits were anaesthetized before mechanical ventilation. A 20 mm Hg increase in intra-abdominal pressure (IAP) was then induced by intraperitoneal infusion of 1.5% glycine solution. Haemodynamic parameters were recorded and the relaxation time constant tau (considered to be the best index of left ventricle relaxation) was calculated. All haemodynamic measurements were recorded at baseline and then after induction of IAH. RESULTS: A 20 mm Hg increase in IAP was not followed by a significant change in arterial pressure, but was associated with increases in central venous pressure (from 2 [-2 to 6] to 7 [-2 to 12] mm Hg, P= 0.03), LV end-diastolic pressure (from 7 [6-8] to 15 [11-19] mm Hg, P= 0.04) and the relaxation time constant tau (from 16 [14-18] to 43 [34-52] ms, P= 0.048). CONCLUSIONS: In this animal study, a 20 mm Hg increase in IAP impaired LV relaxation. Further studies are necessary to identify the causes of this impairment.

[Cardiac metastasis of renal cell carcinoma, a rare location]. / Métastase cardiaque du cancer du rein : site inhabituel.

The renal carcinoma is situated in the third rank of the urologic cancers. It is metastatic in a third of the cases, when we made the diagnosis of the cancer. Lungs, bone, the liver, the suprarenal gland and the brain stay metastatic sites of preference. Some metastatic locations are anecdotal and made the object of some publications. We report the case of a cardiac metastasis of renal carcinoma at an old patient 81 years old operated for cardiac tumor.