Signaling dynamics in coexisting monoclonal cell subpopulations unveil mechanisms of resistance to anti-cancer compounds.

BACKGROUND: Tumor heterogeneity is a main contributor of resistance to anti-cancer targeted agents though it has proven difficult to study. Unfortunately, model systems to functionally characterize and mechanistically study dynamic responses to treatment across coexisting subpopulations of cancer cells remain a missing need in oncology. METHODS: Using single cell cloning and expansion techniques, we established monoclonal cell subpopulations (MCPs) from a commercially available epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer cell line. We then used this model sensitivity to the EGFR inhibitor osimertinib across coexisting cell populations within the same tumor. Pathway-centered signaling dynamics associated with response to treatment and morphological characteristics of the MCPs were assessed using Reverse Phase Protein Microarray. Signaling nodes differentially activated in MCPs less sensitive to treatment were then pharmacologically inhibited to identify target signaling proteins putatively implicated in promoting drug resistance. RESULTS: MCPs demonstrated highly heterogeneous sensitivities to osimertinib. Cell viability after treatment increased > 20% compared to the parental line in selected MCPs, whereas viability decreased by 75% in other MCPs. Reduced treatment response was detected in MCPs with higher proliferation rates, EGFR L858R expression, activation of EGFR binding partners and downstream signaling molecules, and expression of epithelial-to-mesenchymal transition markers. Levels of activation of EGFR binding partners and MCPs' proliferation rates were also associated with response to c-MET and IGFR inhibitors. CONCLUSIONS: MCPs represent a suitable model system to characterize heterogeneous biomolecular behaviors in preclinical studies and identify and functionally test biological mechanisms associated with resistance to targeted therapeutics.

Impact of parathyroidectomy on kidney graft function in post-transplant tertiary hyperparathyroidism: a comparative study.

PURPOSE: Parathyroidectomy to treat tertiary hyperparathyroidism (THPT) is now on a par with calcimimetic treatment. The effects of cinacalcet and parathyroidectomy on kidney transplant function remain controversial. The aim of this study was to evaluate kidney transplant function in THPT patients treated either by parathyroidectomy, cinacalcet, or not treated. METHODS: Between 2009 and 2019, 231 patients with functional grafts presenting THPT, defined either by calcaemia superior to 2.5 mmol/L with elevated PTH level or hypercalcaemia with non-adapted PTH level 1 year after kidney transplantation, were included. Hyperparathyroid patients treated by cinacalcet and parathyroidectomy were matched for age, sex, graft rank, and baseline eGFR with cinacalcet-only and untreated patients. Conditional logistic regression models were used to compare eGFR variations 1 year after parathyroidectomy between operated patients and matched controls. Five-year survivals were compared with the Mantel-Cox test. RESULTS: Eleven patients treated with parathyroidectomy and cinacalcet were matched with 16 patients treated by cinacalcet-only and 29 untreated patients. Demographic characteristics were comparable between groups. Estimated odds ratios for eGFR evolution in operated patients compared with cinacalcet-only and untreated patients were 0.92 [95%CI 0.83-1.02] and 0.99 [0.89-1.10] respectively, indicating no significant impairment of eGFR 1 year after surgery. Five-year allograft survival was not significantly impaired in operated patients. CONCLUSIONS: Parathyroidectomy did not appear to substantially alter or improve graft function 1 year after surgery or 5-year allograft survival. It could be hypothesized that in addition to its known benefits, parathyroidectomy can be safely performed vis-à-vis graft function in tertiary hyperparathyroidism.

PCSK9 is not secreted from mature differentiated intestinal cells.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes lysosomal degradation of the LDL receptor and is a key regulator of cholesterol metabolism. After the liver, the small intestine is the second organ that highly expresses PCSK9. However, the small intestine's ability to secrete PCSK9 remains a matter of debate. While liver-specific PCSK9-deficient mice present no PCSK9 in systemic blood, human intestinal Caco-2 cells can actively secrete PCSK9. This raises the possibility for active intestinal secretion via the portal blood. Here, we aimed to determine whether enterocytes can secrete PCSK9 using in vitro, ex vivo, and in vivo approaches. We first observed that PCSK9 secretion from Caco-2 cells was biphasic and dependent on Caco-2 maturation status. Transcriptional analysis suggested that this transient reduction in PCSK9 secretion might be due to loss of SREBP2-mediated transcription of PCSK9. Consistently, PCSK9 secretion was not detected ex vivo in human or mouse intestinal biopsies mounted in Ussing chambers. Finally, direct comparison of systemic versus portal blood PCSK9 concentrations in WT or liver-specific PCSK9-deficient mice confirmed the inability of the small intestine to secrete PCSK9 into the portal compartment. Altogether, our data demonstrate that mature enterocytes do not secrete PCSK9 and reinforce the central role of the liver in the regulation of the concentration of circulating PCSK9 and consequently of cellular LDL receptors.

Impact of Permanent Post-thyroidectomy Hypoparathyroidism on Self-evaluation of Quality of Life and Voice: Results From the National QoL-Hypopara Study.

OBJECTIVE: The aim of this study was to compare the quality of life (mental health) and voice in patients with or without permanent hypoparathyroidism after total thyroidectomy. SUMMARY BACKGROUND DATA: Permanent hypoparathyroidism is an underestimated complication of thyroid surgery owing to suppression of parathormone secretion. Few studies have evaluated the consequences of hypoparathyroidism on quality of life and none has studied its effects on voice. METHODS: The QoL-hypopara study (ClinicalTrial.gov NCT04053647) was a national observational study. Adult thyroidectomized patients were included between January and June 2020. A serum parathormone level <15 pg/mL >6 months after surgery defined permanent hypoparathyroidism. Patients answered the MOS-36-item short-form health (SF-36), the Voice Handicap Index (VHI) surveys, and a list of questions regarding their symptoms. RESULTS: A total of 141 patients were included, 45 with permanent hypoparathyroidism. The median period between thyroid surgery and the questionnaire was 6 (Q1-Q3 4-11) and 4 (4-5) years in hypoparathyroid patients and controls respectively. Hypoparathyroid patients presented a reduced median mental score ratio (SF-36) [0.88 (Q1-Q3 0.63-1.01) vs 1.04 (0.82-1.13), P = 0.003] and a lower voice quality (incidence rate ratio for total VHI 1.83-fold higher, P < 0.001). In multivariable analysis, hypoparathyroidism [-0.17 (95% confidence interval -0.28 to -0.07), P = 0.002], but not age, female sex, thyroid cancer, or abnormal TSH level, was associated with the reduced mental score ratio. Myalgia, joint pain, paresthesia, tetany, anxiety attack, and exhaustion were the most common symptoms among hypoparathyroid patients (>50%). CONCLUSIONS: Hypoparathyroid patients present significantly impaired quality of life, lower voice quality, and frequent symptoms. These results reinforce the importance of preventing this complication.

Impact of parathyroidectomy on cardiovascular risk in primary hyperparathyroidism: A narrative review.

AIMS: Primary hyperparathyroidism (PHPT), one of the most frequent endocrine disorders, is not only associated with bone and kidney disorders but also with increased cardiovascular risk. This cardiovascular risk is not part of the indication for surgery owing to discordant evidence of the effects of parathyroidectomy (PTX), especially in mild PHPT which is the most common presentation of PHPT. This literature review focuses on the effects of PTX on the cardiovascular risk in PHPT. The MEDLINE database was searched via the PubMed interface, selecting relevant articles published after 1990 in English. DATA SYNTHESIS: In the most recent series, PTX appeared to have a positive impact on cardiovascular morbidity and mortality. Surgery improves arterial hypertension, markers of glucose homeostasis, vascular and cardiac remodeling and electrocardiographic impairments due to classical PHPT. However, the results of surgery on mild PHPT are conflicting. CONCLUSIONS: PTX seems to improve cardiovascular risk in patients presenting the classical form of PHPT. This improvement is correlated with preoperative serum calcium and/or PTH level, depending on the cardiovascular risk factor. However, many aspects of this improvement are not fully understood. Future studies should assess the effects of PTX on nocturnal hypertension, cardiac morphology and functions. The results for mild PHPT are conflicting owing to the limited size of the cohorts included in studies and the lack of randomized trials. Surgery is not currently recommended for patients presenting mild PHPT based on the cardiovascular risk and more studies are needed to better understand the interest of PTX on cardiovascular outcomes.

Utility of a Second 99mTc-MIBI Scintigraphy Before Reoperation for Patients With Persistent Sporadic Primary Hyperparathyroidism: Results of a Retrospective Multicenter Study.

BACKGROUND: Persistent primary hyperparathyroidism (PHPT) occurs in 2.5% to 15% of cases after parathyroidectomy. Few studies have evaluated the best pre-reoperative imaging approaches for persistent sporadic PHPT. This retrospective multicenter study aimed to evaluate the benefit of a second pre-reoperative 99mTc-methoxy-isobutyl-isonitrile (MIBI) scintigraphy for patients with persistent PHPT who had a 99mTc-MIBI before their initial surgery. METHODS: The study enrolled 50 patients with persistent sporadic PHPT who had reoperation between 2006 and 2016 in three French University Hospitals (Angers, Nantes, and La Pitié Salpêtrière-Paris). Preoperative 99mTc-MIBI scan was performed before each operation. RESULTS: After the reoperation, 42 patients (84%) were cured. By the second 99mTc-MIBI, 31 patients (62%) had a removed gland identified. A new pathologic gland was identified by a second 99mTc-MIBI in 25 patients (50%), and this imaging permitted correction of an initial surgical error in six patients (12%). A second 99mTc-MIBI showed a sensitivity of 63%, a specificity of 89%, a positive predictive value (PPV) of 78%, and a negative predictive value (NPV) of 80%. A concordant second 99mTc-MIBI and ultrasonography (17 patients) showed a sensitivity of 70%, a specificity of 81%, a PPV of 70%, and an NPV of 81%. CONCLUSIONS: Performing a second 99mTc-MIBI scan permitted 62% of the persistent PHPT patients to be cured, allowing identification of new pathologic glands in 50% of the cases and correction of an initial surgical error in 12% of the cases, with high specificity and PPV. These results reinforce the fact that a second 99mTc-MIBI scan should be performed at first intention before reoperation of patients with persistent PHPT, regardless of the result from the initial 99mTc-MIBI scan.

Chylous Ascites Management After Pancreatic Surgery.

BACKGROUND: Postoperative chylous ascites (CA) following pancreatic surgery is uncommon. If left untreated, it leads to malnutrition, immunodeficiency and increased postoperative morbidity and mortality. The aim of this study was to seek out risk factors associated with CA onset and conservative treatment (CT) failure in order to determine better management of CA following pancreatic resection. MATERIALS AND METHODS: All consecutive patients who underwent pancreatic surgery between 2004 and 2014 were reviewed retrospectively. Main demographic, clinical and pathological data were searched for CA risk factors. Patients with CA successfully treated with CT alone were compared to those requiring additional bipedal lymphangiography (BPLAG) in order to seek out risk factors associated with CT failure. RESULTS: Fifteen patients (2.4 %) developed CA after pancreatic surgery. Para-aortic lymph node sampling and early enteral feeding were found to be independent risk factors for postoperative CA (OR 6.36, p = 0.024 and OR 12.18, p = 0.02, respectively). CT was successful in ten patients, and five patients required additional BPLAG to achieve CA resolution. Statistical analysis revealed no significant risk factors for CT failure, including total lymph node count (p = 0.196), para-aortic lymph node sampling (p = 0.661) or maximum chyle loss per day (p = 0.758). CONCLUSIONS: Owing to postoperative CA rarity, there is no consensus in treatment. Early on, CT should be attempted in all patients with CA. BPLAG is a safe and efficient procedure that should be discussed earlier in the step-up therapeutic management.

Assessment of the Aldosteronona resolution score as a predictive resolution score of hypertension after adrenalectomy for aldosteronoma in French patients.

PURPOSE: Aldosteronoma Resolution Score (ARS) is a predictive score for cure of hypertension after adrenalectomy for hyperaldosteronism and has been validated in American patients. The aim of the study was to validate this score in a French population. METHOD: Data concerning patients operated from 2002 to 2015 in 7 French University Hospitals were retrospectively collected. Diagnosis of Aldosterone-producing adenoma (APA) was confirmed with clinical and biochemical hyperaldosteronism and adrenal nodule on CT scan. Adrenal venous sampling was performed when CT failed to identify laterality. ARS is based on four variables: female sex, BMI ≤25 kg/m2, duration of hypertension ≤6 years, number of antihypertensive medications ≤2. One point is attributed for the first three and 2 points for the last. Patients were considered as cured if they had no hypertension and no antihypertensive medications at least 6 months after surgery. Patients with bilateral adrenal hyperplasia were excluded. RESULTS: This multicenter study included 310 patients with APA. ARS and follow-up were obtained in 257 patients. 46.6% of patients were cured and potassium serum level was normalized in 97.7%. In multivariate analysis, odds ratio for female sex, BMI ≤25 kg/m2, duration of hypertension ≤6 years, and number of antihypertensive medications ≤2 were 1.60 (p = 0.09), 1.77 (p = 0.04), 1.28 (p = 0.4), 3.41 (p < 0.001), respectively. Cure rate were, respectively, 22.2, 41.4 and 74% for patients with a score ARS 0-1, 2-3, 4-5. The area under the curve (AUC) of ARS was 0.715. CONCLUSION: ARS is not a predictive score efficient enough in a French population maybe due to different metabolic data and genetic conditions.

Transcutaneous Ultrasonography in Early Postoperative Diagnosis of Vocal Cord Palsy After Total Thyroidectomy.

PURPOSE: This study evaluated the efficiency of transcutaneous laryngeal ultrasonography (TLUS) as an alternative to direct flexible laryngoscopy (DFL) in the early postoperative screening of vocal cord palsy (VCP) after total thyroidectomy, performed for benign and non-extensive malignant disease. METHODS: A prospective study was performed on patients who underwent total thyroidectomy between October 2013 and January 2015 at the Nantes University Hospital (France). Patients underwent DFL on postoperative day 1 performed by an otolaryngologist, followed by TLUS performed by a radiologist on postoperative day 1 or 2. RESULTS: One hundred and three (103) patients were included in this study, 17.5% were male and 82.5% were female, with a mean age of 51 ± 12 years. Nine patients (9.5%) were diagnosed with postoperative VCP using DFL of these cases 2 were not completely resolved at 3 months postoperatively. Three cases of VCP (33%) were diagnosed using TLUS. TLUS had a sensitivity of 33% and a negative predictive value (NPV) of 95% for the diagnosis of postoperative VCP. Vocal cords (VC) were unassessable in 27.2% of patients. Unassessable VC were significantly associated with male gender (p = 0.0001), age (p = 0.0001), weight (p = 0.002), operating time (p = 0.032), postoperative drainage (p = 0.001), and thyroid weight (p = 0.001). Independent risk factors in the multivariate analysis were male gender (p = 0.0001) and age (p = 0.0001). In the group of women under 50-year old, TLUS had a sensitivity of 50% and a NPV of 97.4%. CONCLUSION: TLUS sensitivity is insufficient in early postoperative screening of VCP after thyroid surgery. Ultrasonographic VCP diagnosis should be confirmed with DFL.

Management of thyroid nodules incidentally discovered on MIBI scanning for primary hyperparathyroidism.

INTRODUCTION: Parathyroid sestamibi scan is routinely performed before parathyroid surgery. A large number of thyroid cancers take up 99mTc-sestamibi (MIBI). Since 2001, thyroid nodules discovered on sestamibi, nodules >2 cm, and/or with suspicious criteria were resected. The aim of this study was to evaluate the results of this policy. METHODS: All patients operated on for hyperparathyroidism, with a MIBI and cervical ultrasonography (US) with a thyroid resection for nodule, were retrospectively included. RESULTS: From 2001 to 2013, 685 patients were operated on for hyperparathyroidism. Some 137 (85 % females) had both preoperative MIBI and cervical US and a thyroid resection. The mean age was 63.2 ± 12.8 years. Sixty-three patients had a total thyroidectomy and 74 a lobectomy. Thirty-six patients had a thyroid cancer. The median size of cancers was 6.5 mm (0.3-22 mm), and 23 (16.7 %) patients had microcarcinoma. Among the 137 patients, 44 (32 %) had a MIBI+ nodule including 22 cancers. Sixty-one percent of malignant nodules were MIBI+ (22/36). The median size of MIBI+ cancers was 15 mm (9-22 mm) versus 2 mm (0.3-17 mm) for MIBI- cancers (p = 0.03). Twenty-two percent of benign nodules were MIBI+ (22/101). Finally, the sensitivity, specificity, positive predictive value, and negative predictive value of MIBI were 61, 78, 50, and 85 %, respectively. CONCLUSION: Thyroid nodules incidentally discovered on MIBI in hyperparathyroidism patients should be resected.

Quality of life is modestly improved in older patients with mild primary hyperparathyroidism postoperatively: results of a prospective multicenter study.

BACKGROUND: The objectives of this study were to evaluate, in mild primary hyperparathyroidism (pHPT) patients, the quality of life (QoL) using the SF-36 questionnaire before and after parathyroidectomy and to detect preoperatively patients who benefit the most from surgery. Most pHPT patients present a mild pHPT defined by calcemia ≤11.4 mg/dL. For these patients, there is debate about whether they should be managed with surveillance, medical therapy, or surgery. METHODS: A prospective multicenter study investigated QoL (SF-36) in patients with mild pHPT before and after parathyroidectomy in four university hospitals. Laboratory results and SF-36 scores were obtained preoperatively and postoperatively (3, 6, and 12 months). RESULTS: One hundred sixteen patients were included. After surgery, the biochemical cure rate was 98%. Preoperatively, the mental component summary and the physical component summary (PCS) were 38.69 of 100 and 39.53 of 100, respectively. At 1 year, the MCS and the PCS were 41.29 of 100 and 42.03 of 100. The subgroup analysis showed a more significant improvement in patients < 70 years and with calcemia ≥10.4 mg/dL. Postoperative PCS was correlated with age and preoperative PCS: variation = 32.11 - 0.21 × age - 0.4 × preoperative PCS. Men did not improve their MCS postoperatively. Only women with a preoperative MCS <43.6 of 100 showed postoperative improvement. CONCLUSIONS: This study showed, in patients with mild pHPT, an improvement of QoL 1 year after parathyroidectomy. Patients <70 years and with calcemia ≥10.4 mg/dL had a more significant improvement.

Role of preoperative basal calcitonin levels in the timing of prophylactic thyroidectomy in patients with germline RET mutations.

BACKGROUND: The American Thyroid Association (ATA) published recommendations for the timing of prophylactic surgery for medullary thyroid carcinoma based on the specific mutation, patient age, family history, and serum calcitonin levels. The aim of this study was to assess the role of preoperative basal calcitonin (prebCt) levels in predicting the presence of medullary carcinoma of the thyroid in patients with RET mutations. METHODS: We conducted a retrospective study in two endocrine surgery departments. Between 1986 and 2012, a total of 32 patients with RET mutations underwent prophylactic thyroidectomy. The patients were stratified into four ATA risk levels: A, B, C, and D. RESULTS: All of the patients were biologically cured. Microcarcinoma was observed in the final pathology report for four of the 20 patients with normal prebCt (25 %) and for nine of the 12 patients with elevated prebCt (75 %). In the level A group, four patients with normal prebCt and one patient with elevated prebCt presented with microcarcinoma. In the level C group, one patient with normal prebCt and six of the seven patients with elevated prebCt (86 %) presented with microcarcinoma. CONCLUSIONS: PrebCt can predict the presence of microcarcinoma according to surgical pathological analysis. Patients with microcarcinoma can be biochemically and clinically cured using prophylactic thyroidectomy.

[Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion]. / L'excrétion trans-intestinale de cholestérol (TICE) - Une nouvelle voie d'épuration du cholestérol plasmatique.

The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases.

Adjuvant Glucose-Like Peptide 1 Receptor Agonist Therapy for Suboptimal Weight Loss After Bariatric Surgery: a Systematic Review.

Addressing suboptimal weight loss post-bariatric surgery poses a challenge. While glucagon-like peptide 1 receptor agonists (GLP1-RA) show promise in managing obesity, their role as an adjuvant treatment after bariatric surgery remains uncertain. We conducted a systematic literature review focused on the efficacy and safety of GLP1-RA in bariatric surgery patients with insufficient weight loss or distant weight regain. Our literature search identified 1167 articles, with 10 (involving 594 patients) meeting inclusion/exclusion criteria for detailed review. GLP1-RA therapy resulted in 5 to 17% weight loss over 6 to 12 months, with 10-50% experiencing non-severe side effects like nausea. Overall, GLP1-RA emerges as an effective adjuvant therapy for patients experiencing inadequate weight loss or regain after bariatric surgery, offering a viable alternative to revision surgery.

Bariatric Surgery in Patients with Achondroplasia, a Feasibility Study of Two Case Studies.

BACKGROUND: Achondroplasia is a common skeletal dysplasia with a high prevalence of obesity in adulthood. Bariatric surgery has been shown to be effective in treating obesity and related comorbidities, but its feasibility and effectiveness in patients with achondroplasia have not been clearly established. OBJECTIVES: The objective of this study was to evaluate the feasibility and effectiveness of bariatric surgery in patients with achondroplasia. SETTING: This study was performed in France, and bariatric surgeons from the Société Française et Francophone de Chirurgie de l'Obésité et des Maladies Métaboliques (French Francophone Society of Surgery for Obesity or Metabolic Diseases) were asked to participate. METHODS: Two adult women with confirmed achondroplasia and a high BMI were selected for laparoscopic sleeve gastrectomy. Preoperative data were collected, including demographic information, comorbidities, and follow-up at 1, 3, and 6 months and 1 year after surgery. Complications were monitored and recorded. RESULTS: Both patients had good excess weight loss outcomes, with an average excess weight loss of 60.5% 1 year after surgery. One patient had a follow-up of 3 years and an excess weight loss of 44%. The surgery was well-tolerated, and no major complications were observed. CONCLUSIONS: Bariatric surgery is feasible and effective in patients with achondroplasia, with good outcomes for excess weight loss and related comorbidities. These findings suggest that bariatric surgery should be considered a treatment option for patients with achondroplasia and obesity.

Parathyroidectomy Improves Bone Density in Women With Primary Hyperparathyroidism and Preoperative Osteopenia.

CONTEXT: Osteoporosis and/or bone fractures are indications of parathyroidectomy in primary hyperparathyroidism (PHPT), especially in women. However, the benefit of surgery in patients with osteopenia remains unclear. OBJECTIVE: To evaluate bone mineral density (BMD) and bone remodeling biomarkers changes 1 year after parathyroidectomy in women with PHPT. DESIGN: In the prospective, monocentric, observational prospective cohort with primary hyperparathyroidism patients (CoHPT) cohort, women operated for sporadic PHPT since 2016 with ≥1 year follow-up were included. BMD (dual-X ray absorptiometry) and bone remodeling biomarkers [cross-linked C-telopeptide (CTX), procollagen type 1 N-terminal propeptide (P1NP), and bone-specific alkaline phosphatases] were assessed before and 1 year after parathyroidectomy. SETTING: Referral center. PATIENTS: A total of 177 women with PHPT (62.5 ± 13.3 years, 83.1% menopausal, 43.9% osteopenic, and 45.1% osteoporotic) were included. INTERVENTION: Parathyroidectomy. MAIN OUTCOME MEASURE: BMD change between before and 1 year after parathyroidectomy. RESULTS: Parathyroidectomy resulted in significant increase in BMD and decrease in serum bone remodeling biomarker concentrations. In the 72 patients with baseline osteopenia, mean BMD significantly increased at the lumbar spine [+0.05 g/cm2 (95% confidence interval [CI], 0.03-0.07)], the femoral neck [+0.02 g/cm2 (95% CI 0.00-0.04)], the total hip [+0.02 g/cm2 (95% CI 0.01-0.02)], and the forearm [+0.01 (95% CI 0.00-0.02)], comparable to osteoporotic patients. Among osteopenic patients, those with individual BMD gain (>0.03 g/cm2) at ≥1 site had higher preoperative serum CTX, P1NP, and urine calcium concentrations than those without improvement. CONCLUSION: Parathyroidectomy significantly improved BMD and remodeling biomarkers in women with osteopenia, thereby supporting the benefit of parathyroidectomy in these patients. Preoperative serum CTX and P1NP concentrations could be useful to predict expected BMD gain.

Do men improve their bone mineral density 1 year after parathyroidectomy for primary hyperparathyroidism? Results of a prospective study.

BACKGROUND: The impact of parathyroidectomy on bone mineral density in men with primary hyperparathyroidism is poorly known. This study aimed to evaluate the bone mineral density and bone remodeling biomarker changes in men with primary hyperparathyroidism 1 year after parathyroidectomy. METHODS: Men operated for sporadic primary hyperparathyroidism between 2016 and 2022, enrolled in a monocentric prospective cohort, were analyzed. Patients with follow-up <1 year or missing data were excluded. Bone mineral density (dual X-ray absorptiometry) was measured before and 12 months after parathyroidectomy. Bone mineral density change ≥0.03g/cm2 was deemed significant. Bone remodeling biomarkers were serum cross-linked C-telopeptide, procollagen type 1 N-terminal propeptide, and bone-specific alkaline phosphatases. RESULTS: Forty-five men were included (mean age 58.8 ± 13.1 years). Before surgery, 49% had osteopenia, and 11% had osteoporosis. Mean serum calcium and median serum parathyroid hormone levels decreased significantly after surgery (P < .0001). One year after parathyroidectomy, the mean bone mineral density increased significantly at the lumbar spine (+0.04g/cm2 [0.01;0.70], P = .0054), femoral neck (+0.04g/cm2 [0.03;0.05], P < .0001) and total hip (+0.02g/cm2 [0.01;0.03], P = .0002). Considering significant bone mineral density gain (+1 point) and loss (-1 point) at each site, 29/45 patients (64% [95% CI 49;78]) improved. Bone remodeling biomarker concentrations significantly decreased (P < .001). CONCLUSION: Parathyroidectomy positively affects bone mineral density in men with primary hyperparathyroidism, supporting osteopenia as a surgical indication in these patients.

Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy improves lipid and glucose homeostasis in ob/ob mice.

OBJECTIVE: The objective of this study was to compare the general and metabolic impact of single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) with Roux-en-Y gastric bypass (RYGB) in an obese (ob/ob) mouse model. METHODS: 10-week-old male ob/ob mice underwent either SADI-S, RYGB, or laparotomy surgery (Sham group). General and metabolic parameters were assessed during a 5-week period thereafter. RESULTS: SADI-S induced a deeper weight loss ([mean ± SEM] -41.2% ± 3.3%) than RYGB (-5.6% ± 3.5%, p < 0.001) compared with the Sham group (+6.3% ± 1.0%, p < 0.05). A significant food restriction was observed after SADI-S only (-31%, 117.4 ± 10.3 g vs. 170.2 ± 5.2 g of food at day 35 in Sham group mice, p < 0.001). Random-fed glycemia and glucose tolerance were more improved after SADI-S than RYGB. SADI-S decreased plasma cholesterol concentration by 60% (0.49 ± 0.04 g/L vs. 1.40 ± 0.10 g/L in the Sham group at day 35, p < 0.01), significantly more than RYGB (1.04 ± 0.14 g/L, p = 0.018). Plasma sitosterol/cholesterol and campesterol/cholesterol ratios were decreased after SADI-S, suggesting a reduced intestinal cholesterol absorption. SADI-S increased exogenous plasma cholesterol-D7 clearance and fecal elimination, also indicating an increased plasma cholesterol excretion. Studying a pair-fed group demonstrated that calorie restriction alone did not explain the beneficial impact of SADI-S. CONCLUSIONS: SADI-S is associated with a greater improvement in lipid and glucose homeostasis than RYGB in ob/ob mice.

Outcomes of bariatric surgery in the setting of compensated advanced chronic liver disease associated with clinically significant portal hypertension: a multicenter, retrospective, cohort study on feasibility and safety.

BACKGROUND: The obesity epidemic has led to an increase in the proportion of patients with chronic liver disease due to metabolic associated steatosic liver disease and in the prevalence of obesity in patients with cirrhosis. Metabolic and bariatric surgery (MBS) has been proven to determine weight loss, obesity-related medical problems remission, and liver steatosis, inflammation, and fibrosis improvement. However, cirrhosis and portal hypertension are well-known risk factors for increased morbidity and mortality after surgery. The aim of this study is to evaluate the safety of MBS in patients with compensated advanced chronic liver disease (cALCD) and clinically significant portal hypertension (CSPH). MATERIAL AND METHODS: This is an international, multicentric, retrospective study on 63 individuals affected by obesity with cALCD and CSPH who underwent MBS in tertiary referral centers with experts hepatobiliary surgeons between January 2010 and October 2022. The primary endpoint was postoperative mortality at 90 days. The secondary endpoints included postoperative weight loss at last follow-up and postoperative complication rate. In addition, the authors performed subgroup analyses of Child-Pugh (A vs. B) score, MELD (≤9 vs. >9) score, and type of surgery. RESULTS: One patient (1.6%) experienced gastric leakage and mortality. There were three (5%) reported cases of portal vein thrombosis, two (3%) postoperative acute renal failure, and one (1.6%) postoperative encephalopathy. Child-Pugh score A resulted to be a protective factor for intraoperative bleeding requiring transfusion at univariate analysis (OR: 0.73, 95% CI: 0.55-0.97, P =0.046) but not at multivariate analysis. MELD>9 score and the type of surgery did not result to be a risk factor for any postoperative complication. CONCLUSION: MBS is safe in patients with cALCD and CSPH performed in tertiary bariatric referral centers with hepatobiliary expert surgeons. Larger, prospective studies with longer follow-up periods are needed to confirm these results.