Clinical manifestations and outcomes of coronavirus disease-19 in heart transplant recipients: a multicentre case series with a systematic review and meta-analysis

Available data on clinical presentation and mortality of coronavirus disease-2019 (COVID-19) in heart transplant (HT) recipients remain limited. We report a case series of laboratory-confirmed COVID-19 in 39 HT recipients from 3 French heart transplant centres (mean age 54.4 ± 14.8 years; 66.7% males). Hospital admission was required for 35 (89.7%) cases including 14/39 (35.9%) cases being admitted in intensive care unit. Immunosuppressive medications were reduced or discontinued in 74.4% of the patients. After a median follow-up of 54 (19–80) days, death and death or need for mechanical ventilation occurred in 25.6% and 33.3% of patients, respectively. Elevated C-reactive protein and lung involvement ≥50% on chest computed tomography (CT) at admission were associated with an increased risk of death or need for mechanical ventilation. Mortality rate from March to June in the entire 3-centre HT recipient cohort was 56% higher in 2020 compared to the time-matched 2019 cohort (2% vs. 1.28%, P = 0.15). In a meta-analysis including 4 studies, pre-existing diabetes mellitus (OR 3.60, 95% CI 1.43–9.06, I² = 0%, P = 0.006) and chronic kidney disease stage III or higher (OR 3.79, 95% CI 1.39–10.31, I² = 0%, P = 0.009) were associated with increased mortality. These findings highlight the aggressive clinical course of COVID-19 in HT recipients.     

Correlations between grey-level variations in 2D projection images (TBS) and 3D microarchitecture: applications in the study of human trabecular bone microarchitecture

X-ray imaging remains a very cost-effective technique, with many applications in both medical and material science. However, the physical process of X-ray imaging transforms (e.g. projects) the 3-dimensional (3D) microarchitecture of the object or tissue being studied into a complex 2D grey-level texture. The 3D/2D projection process continues to be a difficult mathematical problem, and neither demonstrations nor well-established correlations have positioned 2D texture analysis-based measurement as a valid indirect evaluation of 3D microarchitecture. The trabecular bone score (TBS) is a new grey-level texture measurement which utilizes experimental variograms of 2D projection images. The aim of the present study was to determine the level of correlation between the 3D characteristics of trabecular bone microarchitecture, as evaluated using muCT reconstruction, and TBS, as evaluated using 2D projection images derived directly from 3D muCT reconstruction. Analyses were performed using sets of human cadaver bone samples from different anatomical sites (lumbar spine, femoral neck, and distal radius). Significant correlations were established via standard multiple regression analysis, and via the use of a generic mathematical 3D/2D relationship. In both instances, the correlations established a significant relationship between TBS and two 3D characteristics of bone microarchitecture: bone volume fraction and mean bone thickness. In particular, it appears that TBS permits to accurately differentiate between two 3D microarchitectures that exhibit the same amount of bone, but different trabecular characteristics. These results demonstrate the existence of a robust and generic relationship, taking into consideration a simplified model of a 2D projection image. Ultimately, this may lead to using TBS measurements directly on DXA images obtained in routine clinical practice.     

Isolated micropenis reveals partial androgen insensitivity syndrome confirmed by molecular analysis

Partial androgen insensitivity syndrome （PAIS） is the milder variant of androgen receptor （AR） defects. The subtle effects of AR mutations present in a patient with micropenis, peno-scrotal hypospadias, infertility, clitoromegaly and posterior labial fusion. We studied the association of isolated micropenis with the genetic defects resulting in androgen resistance, that is, AR gene defects and 5-α reductase type 2 （SRD5A2） deficiency. We describe two cases of isolated micropenis： one in a 14-year-old boy and the other in a 3-year-old boy who was followed until he was 10 years old. There were no findings of hypospadias, cryptorchidism or gynecomastia in either of these patients. Serum gonadotrophin and androgen levels were obtained and karyotyping was done. Human chorionic gonadotropin （hCG） stimulation testing assessed the functional capacity of the testes. DNA was extracted from peripheral leukocytes, and all exons of the SRD5A2 and AR genes were amplified by polymerase chain reaction and sequenced. In both patients, baseline testosterone （T） level was low and the values were elevated after hCG testing. The sequence of the SRD5A2 gene was normal in patient 1, and a heterozygous polymorphism, V89L, was found in patient 2. Two known mutations, P390S and A870V, were identified in patients 1 and 2, respectively. Mutations in the AR gene can be associated with isolated micropenis without other features of PAIS, such as hypospadias or gynecomastia. This underlines the importance of including AR gene analysis in the evaluation of isolated micropenis with normal plasma T to ensure proper management of the patient and appropriate genetic counseling for the family.     

Shoulder arthroplasty: evolving techniques and indications

The development of modern shoulder replacement surgery started over half a century ago with the pioneering work done by CS Neer. Several designs for shoulder prostheses are now available, allowing surgeons to select the best design for each situation. When the rotator cuff is intact, unconstrained prostheses produce reliable and reproducible results, with prosthesis survival rates of 97% after 10 years and 84% after 20 years. In patients with three- or four-part fractures of the proximal humerus, the outcome of shoulder arthroplasty depends largely on healing of the greater tuberosity, which is therefore a major treatment objective. Factors crucial to greater tuberosity union include selection of the optimal prosthesis design, flawless fixation of the tuberosities, and appropriate postoperative immobilization. The reverse shoulder prosthesis developed by Grammont has been recognized since 1991 as a valid option for patients with glenohumeral osteoarthritis. Ten-year prosthesis survival rates are 91% overall (including trauma and revisions) and 94% for glenohumeral osteoarthritis with head migration. These good results are generating interest in the reverse shoulder prosthesis as a treatment option in situations where unconstrained prostheses are unsatisfactory (primary glenohumeral osteoarthritis with marked glenoid cavity erosion; comminuted fractures in patients older than 75 years; post-traumatic osteoarthritis with severe tuberosity malunion or nonunion; massive irreparable rotator cuff tears with pseudoparalysis; failed rotator cuff repair; and proximal humerus tumor requiring resection of the rotator cuff insertions).     

Aortic prosthetic ring annuloplasty: a useful adjunct to a standardized aortic valve-sparing procedure?

OBJECTIVE: Dilation of aortic annulus, sinuses of Valsalva, and sinotubular junction (STJ) diameters are the characteristic lesions of aortic root aneurysm. The remodeling technique reduces STJ diameter and creates three neosinuses of Valsalva. Alternatively, the reimplantation technique reduces both annulus and STJ diameters to the detriment of aortic root dynamics. Although the remodeling technique is recognized as the most physiological valve-sparing procedure, aortic annulus dilation may jeopardize its results. A standardized approach that combines an external subvalvular aortic prosthetic ring annuloplasty with the remodeling technique is suggested. METHODS: Eighty-three patients underwent an elective aortic root remodeling procedure, either isolated (group 1, n=34) or combined with an external subvalvular aortic prosthetic ring annuloplasty (group 2, n=49). Preoperative aortic regurgitation was 1.59+/-1.1 (group 1) and 1.97+/-1.3 (group 2) (NS). The aortic annulus was more dilated in group 2 than in group 1 (27+/-2.77 mm vs 26.4+/-2.3 mm, p<0.01). Residual aortic regurgitation > or =grade II was the conversion criteria for aortic valve replacement. RESULTS: Operative mortality was 3.6% (n=3). Intraoperative conversion for valve replacement was 32.7% in group 1 (n=11) versus 4.2% in group 2 (n=2) (p<0.001). In group 1, preoperative annulus diameter was larger for converted than for valve-spared patients (27.6+/-1.7 mm vs 25.2+/-1.5 mm, p<0.02). In group 2, implanted aortic ring significantly reduced annulus diameter (20.6+/-1.8 mm) without significant aortic valve gradient (8.3+/-3 mmHg). Follow-up was 17.2+/-13.4 months (group 1) and 10.41+/-7.95 months (group 2). Reoperation for recurrent aortic regurgitation was 13% in group 1 (n=3) versus 4.2% in group 2 (n=2). Echocardiographic follow-up found residual aortic regurgitation < or =grade I in 17 patients in group 1 (90%) versus 43 patients in group 2 (95.5%) and of grade II in two patients in group 1 (10%) and two patients in group 2 (4.5%). CONCLUSION: The addition of external aortic prosthetic ring annuloplasty improves the remodeling technique's operative reproducibility and short-term results. Therefore, its use as a systematical adjunct to the remodeling procedure is suggested. However, further long-term evaluation comparing this valve-sparing procedure to composite graft replacement should define the best surgical strategy for aortic root aneurysm.     

Bicipital groove orientation: considerations for the retroversion of a prosthesis in fractures of the proximal humerus

The bicipital groove anatomy is well documented, and this groove is used as a landmark to guide retroversion during implantation of a shoulder prosthesis. Whereas the proximal part of the groove is used in osteoarthritis, the distal part is used in fractures. If used in 4-part fracture cases, we must assume that the bicipital groove orientation is constant from proximal to distal. We measured the groove orientation in 40 cadaveric humeri using 3 superimposed computed tomography sections. The reference axis was the transepicondylar axis at the elbow level. The measured angle of the bicipital groove was 55.8 degrees +/- 4.5 degrees at the anatomic neck and 65.1 degrees +/- 3.5 degrees at the surgical neck. This difference (mean of 9.3 degrees, with extremes of -3 degrees and 22.5 degrees) was statistically significant. We confirmed a wide range of variation from 22 degrees to 89 degrees in the orientation of the groove. Because the values listed in the literature for lateral fin placement of a prosthesis have not been measured at the surgical neck level and because of the great variation in groove orientation, we caution surgeons about the use of the bicipital groove as a reliable landmark in shoulder replacement for fractures. Considering the risk of over- or under-retroversion of the prosthesis, we recommend the use of a fracture jig with retroversion set to 20 degrees.     

Quadritherapy vs standard tritherapy immunosuppressant regimen after heart transplantation: A propensity score–matched cohort analysis

After heart transplant, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting calcineurin inhibitors (CNIs) into EVL. The aim of this study was to describe the effects of combining low‐dose EVL and CNIs in maintenance immunosuppression regimen (quadritherapy) and compare it with standard tritherapy associating standard‐dose CNIs, mycophenolate mofetil, and corticosteroids. In the 3‐year registry cohort of heart transplanted patients, those who received quadritherapy were compared with those who received tritherapy. EVL was added after 3 months posttransplant. Three analyses were performed to control for confounders: propensity score matching, multivariable survival, and inverse probability score weighting analyses. Among 213 patients who were included (75 with quadritherapy), propensity score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n = 128), quadritherapy was associated with fewer deaths (3 [4.7%] vs 17 [21.9%], P = .007) and biopsy‐proven acute rejections (15 [23.4%] vs 31 [48.4%], P = .002). These results were confirmed in the overall cohort (n = 213), after multivariable and inverse probability score weighting analyses. Renal function and donor‐specific HLA‐antibodies remained similar in both groups. Low‐dose combination quadritherapy was associated with fewer deaths and rejections, compared with standard immunosuppression tritherapy.     

Preoperative speech and pure-tone audiometry in four types of patients with acoustic neuroma

PURPOSE: The goal of this study was to compare pure-tone and speech audiometry in 4 groups of patients with confirmed unilateral acoustic neuroma in which auditory brainstem responses and transient-evoked otoacoustic emissions were either both normal, abnormal, or one of the tests was abnormal.Material and methods: This study was realized during a preoperative assessment of 65 patients (29 men, 36 women) from 25 to 78 years of age suffering from unilateral acoustic neuroma. The assessment, preceded by tympanometry, included recordings of auditory brainstem responses, transient-evoked otoacoustic emissions, pure-tone audiometry, speech recognition thresholds, and speech discrimination. RESULTS: Some discrepancies between objective and behavioral test results were noticed. Subjects with no otoacoustic emissions but present auditory brainstem responses did not show any significant difference in their speech scores as compared with subjects with both auditory brainstem responses and otoacoustic emissions. CONCLUSIONS: In summary, this study showed that comparable audiometric findings in acoustic neuroma patients can be found regardless of the presence of transient otoacoustic emissions (TEOAEs). TEOAEs are a good screening tool and have been used, like auditory brainstem-evoked responses, as a predictive measure before hearing preservation procedures but cannot predict the audiogram or give information about speech perception. The findings confirm that even if auditory brainstem responses are an extremely useful diagnostic tool for identifying acoustic neuroma, this test provides only giving pieces of information regarding auditory abilities. Also, the pure-tone audiogram gives useful information but has to be used in conjunction with speech audiometry to get an accurate picture of the patient's true auditory abilities.     

Malaria-specific transgenic CD4(+) T cells protect immunodeficient mice from lethal infection and demonstrate requirement for a protective threshold of antibody production for parasite clearance

T cells are important in the immune response to malaria, both for their cytokines and their help for antibody production. To look at the relative importance of these roles, a T-cell receptor (TCR) transgenic mouse has been generated carrying a TCR specific for an epitope of the merozoite surface protein 1 (MSP-1) of the malaria parasite, Plasmodium chabaudi. In adoptive transfer experiments, malaria-specific CD4(+) T cells expand and produce interferon gamma (IFN-gamma) early in infection, but the population contracts quickly despite prolonged persistence of the parasite. MSP-1-specific CD4(+) cells can protect immunodeficient mice from lethal infection; however, the parasite is only completely cleared in the presence of B cells showing that T helper cells are critical. Levels of malaria-specific antibody and the speed of their production clearly correlate with the time of resolution of infection, indicating that a critical threshold of antibody production is required for parasite clearance. Furthermore, T cells specific for a shed portion of MSP-1 are able to provide help for antibody to the protective region, which remains bound to the infected erythrocyte, suggesting that MSP-1 has all of the components necessary for a good vaccine.