Clinique Saint-Luc, Bouge

The role of estradiol (E2; an estrogen) in men needs to be more appreciated. In this review, we address the clinical situations that allow the study of the clinical consequences of E2 deficiency in men and discuss the effects of restoration of levels of this reproductive steroid hormone. In men with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT), E2 is suppressed along with testosterone, leading to side effects affecting the quality of life. These include hot flashes, arthralgia, fatigue, mood changes, cognition problems, weight gain, bone loss, and increased risk of cardiovascular disease. Transdermal E2 alone for ADT has shown equivalent testosterone suppression compared to gonadotropin-releasing hormone (GnRH) agonists while also preventing estrogen-deficiency side effects, including hot flashes and bone loss. Co-treatment of ADT with fetal estrogen estetrol (E4) has shown significant improvements of estrogen-deficiency symptoms. These observations emphasize the need to raise awareness of the importance of estrogens in men among clinicians and the lay public.

Background and Aims Presentation, outcome, and management of females with degenerative mitral regurgitation (DMR) are undefined. We analysed sex-specific baseline clinical and echocardiographic characteristics at referral for DMR due to flail leaflets and subsequent management and outcomes. Methods In the Mitral Regurgitation International Database (MIDA) international registry, females were compared with males regarding presentation at referral, management, and outcome (survival/heart failure), under medical treatment, post-operatively, and encompassing all follow-up. Results At referral, females (n = 650) vs. males (n = 1660) were older with more severe symptoms and higher MIDA score. Smaller cavity diameters belied higher cardiac dimension indexed to body surface area. Under conservative management, excess mortality vs. expected was observed in males [standardized mortality ratio (SMR) 1.45 (1.27–1.65), P < .001] but was higher in females [SMR 2.00 (1.67–2.38), P < .001]. Female sex was independently associated with mortality [adjusted hazard ratio (HR) 1.29 (1.04–1.61), P = .02], cardiovascular mortality [adjusted HR 1.58 (1.14–2.18), P = .007], and heart failure [adjusted HR 1.36 (1.02–1.81), P = .04] under medical management. Females vs. males were less offered surgical correction (72% vs. 80%, P < .001); however, surgical outcome, adjusted for more severe presentation in females, was similar (P ≥ .09). Ultimately, overall outcome throughout follow-up was worse in females who displayed persistent excess mortality vs. expected [SMR 1.31 (1.16–1.47), P < .001], whereas males enjoyed normal life expectancy restoration [SMR 0.92 (0.85–0.99), P = .036]. Conclusions Females with severe DMR were referred to tertiary centers at a more advanced stage, incurred higher mortality and morbidity under conservative management, and were offered surgery less and later after referral. Ultimately, these sex-related differences yielded persistent excess mortality despite surgery in females with DMR, while males enjoyed restoration of life expectancy, warranting imperative re-evaluation of sex-specific DMR management.

Aims The aim of this study is to evaluate the surgical treatment with the best healing rate for patients with proximal femoral unicameral bone cysts (UBCs) after initial surgery, and to determine which procedure has the lowest adverse event burden during follow-up. Methods This multicentre retrospective study was conducted in 20 tertiary paediatric hospitals in France, Belgium, and Switzerland, and included patients aged < 16 years admitted for UBC treatment in the proximal femur from January 1995 to December 2017. UBCs were divided into seven groups based on the index treatment, which included elastic stable intramedullary nail (ESIN) insertion with or without percutaneous injection or grafting, percutaneous injection alone, curettage and grafting alone, and insertion of other orthopaedic hardware with or without curettage. Results A total of 201 patients were included in the study. The mean age at diagnosis was 8.7 years (SD 3.9); 77% (n = 156) were male. The mean follow-up was 9.4 years (SD 3.9). ESIN insertion without complementary procedure had a 67% UBC healing rate after the first operation (vs 30% with percutaneous injection alone (p = 0.027), 43% with curettage and grafting (p = 0.064), and 21% with insertion of other hardware combined with curettage (p < 0.001) or 36% alone (p = 0.014)). ESIN insertion with percutaneous injection presented a 79% healing rate, higher than percutaneous injection alone (p = 0.017), curettage and grafting (p = 0.028), and insertion of other hardware combined with curettage (p < 0.001) or alone (p = 0.014). Patients who underwent ESIN insertion with curettage had a 53% healing rate, higher than insertion of other hardware combined with curettage (p = 0.009). The overall rate of postoperative complications was 25% and did not differ between groups (p = 0.228). A total of 32 limb length discrepancies were identified. Conclusion ESIN insertion, either alone or combined with percutaneous injection or curettage and grafting, may offer higher healing rates than other operative procedures. Limb length discrepancy remains a major concern, and might be partly explained by the cyst’s location and the consequence of surgery. Therefore, providing information about this risk is crucial. Cite this article: Bone Joint J 2024;106-B(5):508–514.

Background The detection of cutaneous metastases (CMs) from various primary tumours represents a diagnostic challenge. Objectives Our aim was to evaluate the general characteristics and dermatoscopic features of CMs from different primary tumours. Methods Retrospective, multicentre, descriptive, cross‐sectional study of biopsy‐proven CMs. Results We included 583 patients (247 females, median age: 64 years, 25%–75% percentiles: 54–74 years) with 632 CMs, of which 52.2% ( n = 330) were local, and 26.7% ( n = 169) were distant. The most common primary tumours were melanomas ( n = 474) and breast cancer ( n = 59). Most non‐melanoma CMs were non‐pigmented ( n = 151, 95.6%). Of 169 distant metastases, 54 (32.0%) appeared on the head and neck region. On dermatoscopy, pigmented melanoma metastases were frequently structureless blue (63.6%, n = 201), while amelanotic metastases were typified by linear serpentine vessels and a white structureless pattern. No significant difference was found between amelanotic melanoma metastases and CMs of other primary tumours. Conclusions The head and neck area is a common site for distant CMs. Our study confirms that most pigmented melanoma metastasis are structureless blue on dermatoscopy and may mimic blue nevi. Amelanotic metastases are typified by linear serpentine vessels and a white structureless pattern, regardless of the primary tumour.

In recent years, advances have been made for treating ascites in patients with cirrhosis. Recent studies have indicated that several treatments that have been used for a long time in the management of portal hypertension may have beneficial effects that were not previously identified. Long‐term albumin infusion may improve survival in patients with cirrhosis and ascites while beta‐blockers may reduce ascites occurrence. Transjugular intrahepatic porto‐systemic shunt (TIPS) placement may also improve survival in selected patients in addition to the control with ascites. Low‐flow ascites pump insertion can be another option for some patients with intractable ascites. In this review, we summarize the latest data related to the management of ascites occurring in cirrhosis. There are still unanswered questions, such as the optimal use of albumin as a long‐term therapy, the place of beta‐blockers, and the best timing for TIPS placement to improve the natural history of ascites, as well as the optimal stent diameter to reduce the risk of shunt‐related side‐effects. These issued should be addressed in future studies.

Introduction TEMPI syndrome is a rare and acquired condition which is characterized by five classical features: telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. The classical treatment is based on bortezomib which can achieve variable responses. Relapse or refractory disease may occur, so other treatment strategies can be proposed. Case Presentation We describe the case of a 54-year-old male followed for a refractory TEMPI syndrome who achieved complete remission after a second-line therapy composed of daratumumab-, lenalidomide-, and dexamethasone-based regimen (DLd). He achieved a complete remission with dramatic improvement of his renal function, restitution of a normal blood oxygen, and disappearance of polycythemia. Conclusion This case highlights the effectiveness of an association of DLd to treat refractory TEMPI syndrome. We also provide arguments for an association between TEMPI syndrome and monoclonal gammopathy of renal significance.

Rationale Unintentional weight loss and malnutrition are common among cancer patients. Malnutrition has been associated with impaired health-related quality of life, less well-tolerated chemotherapy regimens and shorter life duration. In Belgium there is a lack of epidemiological data on malnutrition in oncology patients at advanced stages of the disease. Methods Malnutrition assessment data was collected through a prospective, observational study in 328 patients who started a neoadjuvant anticancer therapy regimen or who started 1st, 2nd or 3rd line anticancer therapy for a metastatic cancer via 3 visits according to regular clinical practice (baseline visit (BV) maximum 4 weeks before start therapy, 1st Follow up visit (FUV1) ± 6 weeks after start therapy, FUV2 ± 4 months after start therapy). Malnutrition screening was evaluated using the Nutritional Risk Screening score 2002 (NRS-2002)and the diagnosis of malnutrition by the GLIM criteria. In addition, SARC-F questionnaire and Fearon criteria were used respectively to screen for sarcopenia and cachexia. Results Prevalence of malnutrition risk at BV was high: 54.5% of the patients had a NRS ≥ 3 (NRS 2002) and increased during the study period (FUV1: 73.2%, FUV2: 70.1%). Prevalence of malnutrition based on physician subjective assessment (PSA) remained stable over the study period but was much lower compared to NRS results (14.0%—16.5%). At BV, only 10% of the patients got a nutrition plan and 43.9% received ≤ 70% of nutritional needs, percentage increased during FU period (FUV1: 68.4%, FUV2: 67.6%). Prevalence of sarcopenia and cachexia were respectively 12.4% and 38.1% at BV and without significant variation during the study period, but higher than assessed by PSA (11.6% and 6.7% respectively). Figures were also higher compared to PSA. There were modifications in cancer treatment at FUV1 (25.2%) and at FUV2 (50.8%). The main reasons for these modifications at FUV1 were adverse events and tolerability. Patient reported daily questionnaires of food intake showed early nutritional deficits, preceding clinical signs of malnutrition, and therefore can be very useful in the ambulatory setting. Conclusions Prevalence of malnutrition and cachexia was high in advanced cancer patients and underestimated by physician assessment. Earlier and rigorous detection of nutritional deficit and adjusted nutritional intake could lead to improved clinical outcomes in cancer patients. Reporting of daily caloric intake by patients was also very helpful with regards to nutritional assessment.

Studies about the duration of the humoral and cellular response following the bivalent booster administration are still scarce. We aimed at assessing the humoral and cellular response in a cohort of healthcare workers that received this booster. Blood samples were collected before the administration of the bivalent booster from Pfizer‐BioNTech and after 14, 28, 90, and 180 days. Neutralizing antibodies against either the D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5 subvariant were measured. The cellular response was assessed by measurement of the release of interferon gamma from T cells in response to an in vitro SARS‐CoV‐2 stimulation. A substantial waning of neutralizing antibodies was observed after 6 months (23.1‐fold decrease), especially considering the XBB.1.5 subvariant. The estimated T 1/2 of neutralizing antibodies was 16.1 days (95% CI = 10.2–38.4 days). Although most participants still present a robust cellular response after 6 months (i.e., 95%), a significant decrease was also observed compared to the peak response (0.95 vs. 0.41 UI/L, p = 0.0083). A significant waning of the humoral and cellular response was observed after 6 months. These data can also help competent national authorities in their recommendation regarding the administration of an additional booster.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The LYMA trial demonstrated the benefit of rituximab maintenance (RM) in first-line young patients with mantle-cell lymphoma. In this prolonged follow-up of 7.5 years (95% CI, 7.4 to 7.7) from inclusion, the median progression-free survival (PFS) and overall survival (OS) for the full population were not reached (NR) with a 7-year PFS of 55.5% (95% CI, 49.5 to 61) and OS of 69.5% (95% CI, 63.8 to 74.5). The EFS remained statistically superior in favor of RM (median NR v 5.8 years, P < .0001; HR, 0.39 [95% CI, 0.52 to 0.6] and 7-year estimate, 76.2% versus 46% for RM and observation, respectively). Similarly, RM prolonged PFS (estimated PFS at 7 years, 78.5% v 47.4% and HR, 0.36 [95% CI, 0.23 to 0.56] for RM and observation, respectively, P < .0001). The 7-year OS estimate was 83.2% versus 72.2%, respectively ( P = .088, HR, 0.63 [95% CI, 0.37 to 1.08]). Cause of death was not significantly distinct between the two groups, with lymphoma being the leading cause with a very low rate of infection-related death. Overall, the PFS benefit of RM after autologous stem cell transplantation remains after 7-year follow-up, and RM was not associated with an increase in infection-related mortality, making this strategy a safe standard of care with long-term follow-up.

Background: The EFLM Task Force Preparation of Labs for Emergencies (TF-PLE) created a survey that has been distributed to its members for gathering information on the key hazards experienced by European medical laboratories during the COVID-19 pandemic. Methods: The survey was distributed to over 12,000 potential contacts (laboratory workers) via an EFLM newsletter, with responses collected between May 8 and June 8, 2023. Results: Two hundred replies were collected and examined from European laboratories. 69.7% and 78.1% of all responders said they were short on non-COVID and COVID reagents, respectively. Exactly half of respondents (50.0%) said that they could not complete all laboratory tests required for a specific period, but this figure climbed to 61.2% for COVID tests. Finally, 72.3% of respondents expressed exhaustion during the pandemic, and 61.2% reported increasing patient hostility. Conclusions: The COVID-19 pandemic had a significant impact on laboratory medicine in Europe. Cultural change, proactive planning, and even re-engineering in some parts of the laboratory industry may thus be necessary to prepare for future challenges.

AZD7442 (150 mg of tixagevimab plus 150 mg cilgavimab) has been approved for the pre-exposure prophylaxis of COVID-19 and for the treatment of adults and adolescents with COVID-19 who do not require supplemental oxygen and who are at increased risk of severe COVID-19. In this study, two patients received AZD7442 for immunoprophylaxis. A cohort of subject who had received the BNT162b2 mRNA COVID‐19 vaccine has been included to compare strategies. Neutralizing antibodies (NAbs) against several variants were measured (wild-type, Alpha, Beta, Gamma, Delta, Omicron BA.5 and XBB.1.5). Binding antibodies have also been measured. NAbs T 1/2 for AZD7442 was 8.1 days (95% CI: 5.1–19.5 days) and was 11.8 days (95% CI: 7.9–23.7 days) for the primo-vaccination cohort. The time to reach NAbs negativity was 108.3 days (95% CI: 66.9–130.7) for AZD7442 compared to 95.4 days (95% CI: 31.0–119.7 days) for primo-vaccination cohort. The time to reach NAbs negativity differs between variants with the maximum value obtained for the Alpha (i.e., 101.1 days (95% CI: 30.0–135.4 days)) and the minimum obtained for the Beta (i.e., 61.2 days (95% CI: 37.8–77.1 days)). Our results reinforces the need of reviewing the use of AZD7442 in relation to variant of concern and potentially adapting its administration schedule. AZD7442 could be indicated for short-term prophylaxis in frail patients who may be acutely exposed to SARS-CoV-2.

Introduction Gautier et al. demonstrated that a compression in the left paratracheal region (left paratracheal pressure, LPP) can be used to seal the oesophagus. However, at this level, the left common carotid artery is very close to the carotid that could be affected during the manipulation. This study aimed to assess the hemodynamic effects of LPP on the carotid blood flow. Methods We prospectively included 47 healthy adult volunteers. We excluded pregnant women and people with anomalies of the carotid arteries. The common and internal carotid arteries were preliminarily studied with ultrasounds to exclude atheromatous plaques or vascular malformation. A planimetry of the common and internal carotid arteries was performed. Doppler echography served to measure the peak systolic (PSV) and end‐diastolic velocities (EDV) in the common and internal carotid arteries. All measurements were repeated while applying LPP. Results Forty‐seven participants were enrolled (32 women; mean [SD] age: 42 [13] years). The mean PSV difference [95% CI] in the left common carotid artery before and after LPP at the group level was −15.30 [−31.09 to 0.48] cm s ⁻¹ ( p = .14). The mean surface difference [95% CI] in the left common carotid artery before and after LPP was 24.52 [6.11–42.92] mm ² ( p = .11). Similarly, the same surface at the level of the left internal carotid artery changed by −18.89 [−51.59 to 13.80] mm ² after LPP ( p = .58). Conclusions Our results suggest that LPP does not have a significant effect on carotid blood flow in individuals without a carotid pathology. However, the safety of the manoeuvre should be evaluated in patients at risk of carotid anomalies.

IgG4-related sclerosing cholangitis is a special type of cholangiopathy often associated with autoimmune pancreatitis. In this article, we report an unusual case of IgG4-SC limited to the common hepatic duct and associated with pseudo tumoral liver lesions, but without evidence of pancreatic involvement. Corticosteroid therapy was rapidly effective and allowed normalization of liver tests.

Introduction: In alcohol-associated cirrhosis, an accurate estimate of the risk of death is essential for patient care. We developed individualized prediction charts for 5-year liver-related mortality among outpatients with alcohol-associated cirrhosis that take into account the impact of abstinence. Methods: We collected data on outpatients with alcohol-associated cirrhosis in a prospective registry. The model was derived, internally and externally validated, and compared with the Child-Pugh and the Model For End-Stage Liver Disease (MELD) scores. Results: A total of 527 and 127 patients were included in the derivation and validation data sets, respectively. A model was developed based on the 3 variables independently associated with liver-related mortality in multivariate analyses (age, Child-Pugh score, and abstinence). In the derivation data set, the model combining age, Child-Pugh score, and abstinence outperformed the Child-Pugh and the MELD scores. In the validation data set, the Brier score was lower for the model (0.166) compared with the Child-Pugh score (0.196, p = 0.008) and numerically lower compared with the MELD score (0.190) (p = 0.06). The model had the greatest AUC (0.77; 95% CI 0.68-0.85) compared with the Child-Pugh score (AUC = 0.66; 95% CI 0.56-0.76, p = 0.01) and was numerically higher than that of the MELD score (AUC = 0.66; 95% CI 0.56-0.78, p = 0.06). Also, the Akaike and Bayesian information criterion scores were lower for the model (2163; 2172) compared with the Child-Pugh (2213; 2216) or the MELD score (2205; 2208). Conclusion: A model combining age, Child-Pugh score, and abstinence accurately predicts liver-related death at 5 years among outpatients with alcohol-associated cirrhosis. In this study, the model outperformed the Child-Pugh and the MELD scores, although the AUC and the Brier score of the model were not statically different from the MELD score in the validation data set.

Background and aims: We describe mortality-related risk factors of inpatients with diabetes and coronavirus disease 2019 (COVID-19) in Belgium. Methods: We conducted a multicenter retrospective study from March to May, 2020, in 8 Belgian centers. Data on admission of patients with diabetes and COVID-19 were collected. Survivors were compared to non-survivors to identify prognostic risk factors for in-hospital death, using multivariate analysis in both the total population and in the subgroup of patients admitted to the intensive care unit (ICU). Results: The study included 375 patients. The mortality rate was 26.4% (99/375) in the total population and 40% (27/67) in the ICU. Multivariate analysis identified older age (HR 1.05 [CI 1.03-1.07], p <0.0001) and male gender (HR 2.01 [1.31-3.07], p 0.0013) as the main independent risk factors for in-hospital death in the total population. Use of metformin (HR 0.51 [0.34-0.78], p 0.0018) and renin-angiotensin-aldosterone system blockers (HR 0.56 [0.36-0.86], p 0.0088) before admission were independent protective factors. In the ICU, chronic kidney disease (CKD) was identified as an independent risk factor for death (HR 4.96 [2.14-11.5], p <0.001). Conclusion: In-hospital mortality due to the first wave of the COVID-19 pandemic in Belgium was high in patients with diabetes. We found that advanced age and male gender were independent risk factors for in-hospital death. We also showed that metformin use before admission was associated with significantly lower COVID-19-related in-hospital mortality. Finally, we showed that CKD is a COVID-19-related mortality risk factor in patients with diabetes admitted to the ICU.