Cost-Effectiveness of Nivolumab Plus Ipilimumab for the First-Line Treatment of Intermediate/Poor-Risk Advanced and/or Metastatic Renal Cell Carcinoma in Switzerland.

OBJECTIVE: This study assessed the cost-effectiveness of nivolumab plus ipilimumab versus both sunitinib and pazopanib for the treatment of first-line unresectable advanced renal cell carcinoma (aRCC) from a healthcare system perspective in Switzerland. METHODS: A three-state partitioned survival model, consisting of progression-free, progressed disease, and death, was constructed. Efficacy estimates were based on data from the CheckMate 214 trial (NCT02231749) with a minimum follow-up of 42 months. Two Swiss oncologists were consulted to determine disease management resource use. Costs were derived from the Swiss tariff lists for outpatient (TARMED Online Browser 1.09) and inpatient (2020 data from Swiss diagnosis-related groups) treatments. Drug acquisition costs (ex-factory prices) were obtained from the March 2020 price list published by the Swiss Federal Office of Public Health. Treatment-specific EQ-5D-3L-based utilities were derived from CheckMate 214 using a French value set as a proxy for Switzerland. The model utilized a 1-week cycle length and a 40-year time horizon, with costs and effects discounted by 3.0% per annum. One-way sensitivity analyses, probabilistic analysis, and scenario analyses assessed the robustness of the results. RESULTS: Nivolumab plus ipilimumab yielded incremental 1.43 life-years and 1.36 lifetime discounted quality-adjusted life-years (QALYs) relative to sunitinib and pazopanib at an additional cost of 147,453 Swiss Francs (CHF) and CHF145,643, respectively. With an incremental cost-utility ratio of CHF108,326 per QALY gained versus sunitinib, and CHF106,996 per QALY gained versus pazopanib, the nivolumab plus ipilimumab combination can be considered a cost-effective option for the treatment of patients with aRCC in Switzerland, with a willingness-to-pay threshold of CHF200,000. Sensitivity and scenario analyses confirmed the robustness of the deterministic results. CONCLUSIONS: This study showed that nivolumab plus ipilimumab, which represents one of the standard-of-care first-line treatments for intermediate- or poor-risk aRCC patients, is a life-extending and cost-effective treatment option for patients in Switzerland.

Characteristics and outcomes of sepsis patients with and without COVID-19.

BACKGROUND: The aim of this study was to describe and compare clinical characteristics and outcomes in critically ill septic patients with and without COVID-19. METHODS: From February 2020 to March 2021, patients from surgical and medical ICUs at the University Hospital Dresden were screened for sepsis. Patient characteristics and outcomes were assessed descriptively. Patient survival was analyzed using the Kaplan-Meier estimator. Associations between in-hospital mortality and risk factors were modeled using robust Poisson regression, which facilitates derivation of adjusted relative risks. RESULTS: In 177 ICU patients treated for sepsis, COVID-19 was diagnosed and compared to 191 septic ICU patients without COVID-19. Age and sex did not differ significantly between sepsis patients with and without COVID-19, but SOFA score at ICU admission was significantly higher in septic COVID-19 patients. In-hospital mortality was significantly higher in COVID-19 patients with 59% compared to 29% in Non-COVID patients. Statistical analysis resulted in an adjusted relative risk for in-hospital mortality of 1.74 (95%-CI=1.35-2-24) in the presence of COVID-19 compared to other septic patients. Age, procalcitonin maximum value over 2 ng/ml, need for renal replacement therapy, need for invasive ventilation and septic shock were identified as additional risk factors for in-hospital mortality. CONCLUSION: COVID-19 was identified as independent risk factor for higher in-hospital mortality in sepsis patients. The need for invasive ventilation and renal replacement therapy as well as the presence of septic shock and higher PCT should be considered to identify high-risk patients.

Case Report: New-Onset Retinal Migraine After Transseptal Catheterization.

BACKGROUND: While new-onset migraine headaches and binocular visual aura have been reported after transseptal catheterization (TSC), this case suggests that retinal aura may emerge also after this procedure. CASE DESCRIPTION: This 38-year-old male with paroxysmal atrial fibrillation had received TSC and cryoablation, and subsequently developed isolated monocular aura phenomena. The first episode happened a few hours after the intervention and was not accompanied by headache or other aura phenomena. The patient's history was negative for migraine. Brain magnetic resonance imaging demonstrated 2 lacunar diffusion restrictions in the left medial cerebral artery territory that were most likely catheterization related. Over the next 14 days, 3 additional, stereotyped episodes (duration = 20-30 minutes) with zigzag lines and flickering small bright dots in the central visual field of one eye (moving laterally) occurred. A central scotoma was noted during one episode. CONCLUSIONS: This is the first case with retinal aura phenomena meeting International Classification of Headache Disorders diagnostic criteria for retinal migraine, suggesting that this rare migraine variant can be triggered by TSC.

Long-Term Results After Stapled Hemorrhoidopexy: A 15-Year Follow-Up.

BACKGROUND: The stapled hemorrhoidopexy is reported to have a low recurrence while treating the major hemorrhoidal symptoms of bleeding and prolapse. The aim of this study is to obtain long-term results on the outcome of the stapled hemorrhoidopexy. METHODS: All patients with a hemorrhoidal disease grade III, who underwent stapled hemorrhoidopexy from May 1999-December 2003, were included. Data collection was based on a standardized telephone interview. In the questionnaire, we recorded information regarding the postoperative recurrence and severity of hemorrhoidal symptoms (defined as bleeding, prolapse, burning, itching and moisture), further hemorrhoidal treatments and functional results (incontinence, fecal urgency and outlet obstruction) as well as patients' satisfaction. RESULTS: Of the 257 patients, who underwent stapled hemorrhoidopexy, follow-up data were available in 140 patients. In 47.4% of the patients, a recurrence of at least one hemorrhoidal symptom was registered, whereas this recurrence was observed in 47.3% of these patients more than 10 years postoperatively. A surgical re-intervention was necessary in 15.2%. We found a postoperative new incontinence in 15.5%, a fecal urgency in 28.0% and an outlet obstruction in 9.4%. Of all patients, 62.3% were "very satisfied" with the operation. CONCLUSIONS: The results of the study revealed a relatively high recurrence of hemorrhoidal symptoms after a mean follow-up of 15 years with a high recurrence rate more than 10 years postoperatively. In consideration of not negligible risk of incontinence, fecal urgency and outlet obstruction, the indication for a stapled hemorrhoidopexy should be made well considered. However, patients' satisfaction is very high.

Minimally Invasive Parathyroidectomy without Intraoperative PTH Performed after Positive Ultrasonography as the only Diagnostic Method in Patients with Primary Hyperparathyroidism.

BACKGROUND: A positive and concordant result of at least two diagnostic modalities is generally recommended prior to focused parathyroidectomy. The aim of this study was to analyze the results of surgery and the accurateness of preoperative ultrasonography (US) as single localization modality in patients who underwent parathyroidectomy without the adjunct of intraoperative Parathormone (PTH) measurement. METHODS: The cases with a preoperative US as the only localization technique, who underwent parathyroidectomy between 10/1999 and 12/2017, were selected from a prospectively maintained database. Therefore, a total number of 242 patients with a mean age of 58.6 ± 13.7 years were included in the present study. US was performed by referral endocrinologist or by the surgeon during office visits. RESULTS: The overall "cure rate" was 99.2% (240 out of 242 patients). In 228/242 patients (94.2%), a drop of perioperative PTH levels consistent with the definition of cure was observed on the day of surgery. In four of the remaining 14 patients, healing was confirmed by PTH level dropping into the normal range on the first postoperative day. Eight patients were cured after a reoperation was performed at our department. Postoperative complications included one case of permanent recurrent laryngeal nerve palsy (0.4%). CONCLUSIONS: If performed by an experienced endocrinologist and/or endocrine surgeon, a positive US could be the only preoperative localization study in patients with pHPT. Moreover, the add-value of intraoperative PTH is limited. Major advantages of US are a very high accuracy, the ease of performance (accessibility) and its cost-effectiveness compared with Sesta-MIBI scintigraphy.

Influence of Parathyroidectomy on Bone Metabolism and Bone Pain in Patients with Secondary Hyperparathyroidism.

BACKGROUND: After parathyroidectomy (PTX), hungry bone syndrome leads to hypocalcemia due to bone remineralization. The aim of this pilot study was to analyze changes in markers of bone metabolism in patients with secondary hyperparathyroidism (sHPT) after PTX and to correlate these markers with bone pain measured with a validated questionnaire. MATERIALS AND METHODS: All patients who underwent PTX for sHPT between March 2010 and February 2012 at out institution were included in this prospective observational pilot study. At the day before surgery and on the 3rd day thereafter, levels of parathyroid hormone (PTH), calcium, osteocalcin, alkaline phosphatase (AP), bone-specific AP (BAP), tartrate-resistant acid phosphatase 5b (TRAP5b), osteoprotegerin (OPG), sclerostin, fibroblast growth factor 23, and Klotho were measured. Additionally, all patients were requested to answer the Brief Pain Inventory preoperatively and on the 5th postoperative day. RESULTS: A total of 35 patients with a mean age of 49.8 years were analyzed. A significant difference between the pre- and postoperative values could be detected in PTH, calcium, BAP, TRAP5b, and sclerostin. The highest correlation of laboratory markers with bone pain was found for preoperative PTH (r = 0.3), postoperative OPG (r = 0.4), postoperative BAP (r = -0.4), and postoperative Klotho (r = -0.4). CONCLUSIONS: The present study revealed significant perioperative changes in PTH, BAP, sclerostin, and TRAP5b after PTX. These markers may serve as laboratory markers to monitor bone metabolism in patients with sHPT. PTH, OPG, and sclerostin were the parameters with the closest correlation to bone pain. However, larger prospective trials with a longer follow-up are required to confirm these results.

Gene therapy with the TRF1 telomere gene rescues decreased TRF1 levels with aging and prolongs mouse health span.

The shelterin complex protects telomeres by preventing them from being degraded and recognized as double-strand DNA breaks. TRF1 is an essential component of shelterin, with important roles in telomere protection and telomere replication. We previously showed that TRF1 deficiency in the context of different mouse tissues leads to loss of tissue homeostasis owing to impaired stem cell function. Here, we show that TRF1 levels decrease during organismal aging both in mice and in humans. We further show that increasing TRF1 expression in both adult (1-year-old) and old (2-year-old) mice using gene therapy can delay age-associated pathologies. To this end, we used the nonintegrative adeno-associated serotype 9 vector (AAV9), which transduces the majority of mouse tissues allowing for moderate and transient TRF1 overexpression. AAV9-TRF1 gene therapy significantly prevented age-related decline in neuromuscular function, glucose tolerance, cognitive function, maintenance of subcutaneous fat, and chronic anemia. Interestingly, although AAV9-TRF1 treatment did not significantly affect median telomere length, we found a lower abundance of short telomeres and of telomere-associated DNA damage in some tissues. Together, these findings suggest that rescuing naturally decreased TRF1 levels during mouse aging using AAV9-TRF1 gene therapy results in an improved mouse health span.

Implementation and effects of pulse-contour- automated SVV/CI guided goal directed fluid therapy algorithm for the routine management of pancreatic surgery patients.

BACKGROUND: Goal directed fluid management in major abdominal surgery has shown to reduce perioperative complications. The approach aims to optimize the intravascular fluid volume by use of minimally invasive devices which calculate flow-directed variables such as stroke volume (SV) and stroke volume variation (SVV). OBJECTIVE: We aimed to show the feasibility of routinely implementing this type of hemodynamic monitoring during pancreatic surgery, and to evaluate its effects in terms of perioperative fluid management and postoperative outcomes. METHODS: All patients undergoing pancreatic surgery at a university hospital during two successive 12 months periods were included in this retrospective cohort analysis. Twelve months after the implementation of a standard operating procedure for a goal directed therapy (GDT, N = 45) using a pulse contour automated hemodynamic device were compared with a similar period before its use (control, N = 31) regarding mortality, length of hospital and ICU stay, postoperative complications and the use of fluids and vasopressors. RESULTS: Overall, 76 patients were analysed. Significantly less crystalloids were used in the GDT group. Patients receiving GDT showed significantly fewer severe complications (insufficiency of intestinal anastomosis: 0 vs. 5 (P = 0.0053) and renal failure: 0 vs. 4 (P = 0.0133). Mortality for pancreatic surgery was 1 vs. 3 patients, (P = 0.142), and length of stay (LOS) in the intensive care unit (ICU) was 4.38 ± 3.63 vs. 6.87 ± 10.02 (P= 0.0964) days. Use of blood products was significantly less within the GDT group. CONCLUSIONS: Implementation of a SOP for a GDT in the daily routine using flow-related parameters is feasible and is associated with better outcomes in pancreatic surgery.

Long-term outcome of sporadic and FAP-associated desmoid tumors treated with high-dose selective estrogen receptor modulators and sulindac: a single-center long-term observational study in 134 patients.

Aim of this study is to evaluate the outcome of long-term conservative treatment with sulindac and high-dose selective estrogen receptor modulators (SERMs) for sporadic and FAP-associated desmoid tumors. Desmoids are very rare tumors in the general population but occur frequently in FAP patients, being encountered in 23-38 %. Treatment of desmoids is still most controversial since response cannot be predicted and they are prone to develop recurrence. This study included all desmoid patients that were treated and followed at our institution and had completed at least 1 year of treatment. Response was defined as stable size or regression of desmoid size between two CT or MRI scans. A total of 134 patients were included. 64 (47.8 %) patients had a confirmed diagnosis of FAP, 69 (51.5 %) patients were sporadic. Overall 114 (85.1 %) patients showed regressive or stable desmoid size. Patients with previous history of multiple desmoid-related surgeries showed less-favorable response. The mean time to reach at least stable size was 14.9 (±9.1) months. After regression or stabilization, medication was tapered in 69 (60.5 %) of the treated patients with only one long-term recurrence after >10 years. The results of this study fortify the role of sulindac and high-dose SERMs as an effective and safe treatment for both, sporadic and FAP-associated desmoid tumors. While invasive treatment frequently results in high recurrence rates, high morbidity and high mortality, this conservative treatment is successful in most patients. The recurrence rate is negligible with no desmoid-related mortality in this large series. Therefore surgical resection, especially for mesenteric desmoids, should be deferred favoring this convincingly effective, well tolerated regimen.

Immunohistochemical Expression of E-Cadherin in Atypical Parathyroid Adenoma.

BACKGROUND: Atypical parathyroid adenoma (APA) is a rare entity, sharing clinical symptoms like solid palpable mass in the neck, laboratory changes with very high serum calcium and parathyroid hormone levels, and some histopathological features with parathyroid carcinomas (PC). However, clinical behavior of APA seems to comply with benign parathyroid tumors (PA). There is some evidence that loss of the membranous staining pattern of E-Cadherin (E-Cad) suggests a key role of epithelial mesenchymal transition in the tumorigenesis of PC. Thus, the aim of this study was to compare clinical and surgical characteristics and immunohistochemical expression of E-Cad in APA, PC, and PA. METHODS: Data of patients who underwent surgery for primary hyperparathyroidism (pHPT) between 1985 and 2010 were retrospectively evaluated. All data were analyzed with special regard to distinctive criteria of APA, including trabecular growth, broad fibrous bands, nuclear atypia, mitosis, pseudocapsular invasion or strong adherence to the surrounding tissue, and potential invasive growth of a grossly altered and enlarged parathyroid gland. In addition, laboratory and clinical data were evaluated and additional immunohistochemical staining with E-Cad was performed in suspicious APA patients with available tissue. RESULTS: In 68 patients (39 female, 29 male), the parathyroid tumor was suspicious for APA. In 46 patients, a bilateral cervical exploration was performed. 15 patients underwent an en bloc resection including a hemithyroidectomy and lymphonodular dissection of the ipsilateral central compartment due to the malignant macroscopic aspect of the parathyroid. In seven patients, a focused parathyroid resection was done. The available parathyroid tissue of 38 APA patients was immunopositive for membranous E-Cad staining. During follow-up, only one patient with a successful initial surgery suffered from recurrent pHPT due to another solitary PA 10 years after initial surgery but without evidence of malignancy. CONCLUSIONS: In contrast to PC, parathyroid tumors suspicious for APA are characterized by a strong membranous E-Cad staining and, like PA, by a benign clinical course.

Prophylactic surgery in familial adenomatous polyposis (FAP)--a single surgeon's short- and long-term experience with hand-assisted proctocolectomy and smaller J-pouches.

PURPOSE: Prophylactic proctocolectomy with an ileoanal neo-reservoir is the established procedure in non-attenuated familial adenomatous polyposis (FAP). Traditionally, the ileal J-pouch is created by doubling 15 cm of the terminal ileum. Pouch inlet problems are not infrequently encountered in longer pouches. On this rationale, this series reports on the functional outcome and quality of life (QoL) following standardized construction of a shorter J-pouch with a limb of 8-9 cm length. METHODS: All patients of a single-surgeon series with FAP who underwent hand-assisted laparoscopic proctocolectomy and small ileal pouch-anal anastomosis as the primary procedure between 10/2005 and 04/2010 and responded to the questionnaire were included and retrospectively analyzed. RESULTS: A total of 46 patients (78 %) out of the consecutive series who underwent operation in this period were included in the study. After a mean follow-up of 38 months, 40/46 patients (87 %) did not report any incontinence and 3 patients (6.5 %) complained about occasional nocturnal incontinence (3 failed to answer this question). The mean stool frequency per 24 h was 6.25. No significant difference was encountered between the QoL outcome of our patients versus the German normative population. Comparable results were achieved in a study analyzing the long-term results in FAP patients with a 15-cm pouch. CONCLUSIONS: Smaller, 8-9 cm J-pouches show excellent functional results both in short- and in long-term results. The hand-assisted procedure was safe and no conversions were required. QoL is equal to a normative population, as it is in a series of patients with larger J-pouches.

Reduction of radiation exposure during ablation of atrial fibrillation.

AIMS: Pulmonary vein isolation (PVI) during ablation of atrial fibrillation (Afib) may be associated with long fluoroscopy duration. Although most current publications report on fluoroscopy time (FT), the dose-area product (DAP) may be a more valuable parameter for depicting radiation exposure. The aim of our study was to describe a method to reduce DAP by simple means during ablation of Afib. METHODS: Patients undergoing Afib ablation using a three-dimensional (3D) mapping system were assigned to two fluoroscopy protocols: (1) standard settings with 7.5 pictures/s and collimation to the heart, fluoroscopy as needed for the convenience of the operator (standard group, SG); and (2) strict collimation to the left atrium, a frame rate of 4 pictures/s, shortened pulmonary vein angiography sequences, and maximal orientation by the 3D mapping system (redDAP group). The primary endpoint was DAP. RESULTS: The study comprised 206 patients, who were assigned to the SG (n = 101, 49 %) or to the redDAP group (n = 105, 51 %). Mean FT was significantly reduced from 29.9 ± 11.3 min (SG) to 13.3 ± 8.3 min (redDAP group); mean DAP was reduced by approximately 90 % from 8,690 ± 5,727 to 837 ± 647 cGycm(2). The groups did not differ significantly in body mass index (28.8 ± 4.1 vs. 29.0 ± 5.0). PVI could be achieved in 98 of 101 patients (97 %) from the SG group and in all patients (100 %) from the redDAP group. Procedure time was significantly longer in the redDAP group (160.9 ± 35.7 vs. 138.1 ± 34.3 min). CONCLUSION: Radiation exposure during Afib ablation procedures can be reduced with simple means by strict collimation to the left atrium, a frame rate of 4 pictures/s, shortened pulmonary vein angiography sequences, and maximal 3D orientation.

Sox4 links tumor suppression to accelerated aging in mice by modulating stem cell activation.

Sox4 expression is restricted in mammals to embryonic structures and some adult tissues, such as lymphoid organs, pancreas, intestine, and skin. During embryogenesis, Sox4 regulates mesenchymal and neural progenitor survival, as well as lymphocyte and myeloid differentiation, and contributes to pancreas, bone, and heart development. Aberrant Sox4 expression is linked to malignant transformation and metastasis in several types of cancer. To understand the role of Sox4 in the adult organism, we first generated mice with reduced whole-body Sox4 expression. These mice display accelerated aging and reduced cancer incidence. To specifically address a role for Sox4 in adult stem cells, we conditionally deleted Sox4 (Sox4(cKO)) in stratified epithelia. Sox4(cKO) mice show increased skin stem cell quiescence and resistance to chemical carcinogenesis concomitantly with downregulation of cell cycle, DNA repair, and activated hair follicle stem cell pathways. Altogether, these findings highlight the importance of Sox4 in regulating adult tissue homeostasis and cancer.

Initial surgery for benign primary hyperparathyroidism: an analysis of 1,300 patients in a teaching hospital.

BACKGROUND: Success rates of initial surgery for primary hyperparathyroidism (pHPT) are greater than 95 % in specialized centers, mostly referring to single-surgeon experiences. The present study was performed to identify changes in clinical manifestations, diagnostic procedures, surgical strategies, and outcome of initial parathyroid interventions in a teaching hospital during the past 25 years with special regard to the surgical expertise. METHODS: Clinical data of patients who underwent an initial neck exploration for benign pHPT between 1985 and 2010 at the University hospital Marburg were retrospectively evaluated. All data were analyzed particularly with regard to the implementation of additional pre- and intraoperative procedures and to the particular surgical strategy. In addition, operative results were furthermore analyzed with regard to the experience of the responsible surgeons. RESULTS: An initial neck exploration for benign pHPT was performed in 1,300 patients. Of these, 1,035 patients had a bilateral cervical exploration (BCE) and 265 patients had a focused, minimally invasive parathyroidectomy (MIP). Cure rates did not differ between focused surgeries and BCE (98.9 vs. 98.3%, p = 0.596) after a mean follow-up of 33.4 (± 44.3) months. Postoperative transient hypoparathyroidism was significantly lower in the MIP group (11 vs. 47%, p < 0.0001). The rate of permanent recurrent laryngeal nerve palsies (0.4 vs. 2%, p = 0.064) and nonsurgical complications (0 vs. 1.4%, p = 0.0875) tended to be lower in the MIP group. Success and complication rates of chief surgeons (n = 2), attending surgeons (n = 20), and residents (56 < 3 years, 30 > 3 years) were similar, despite a significantly shorter operating time in the chief surgeon group (p < 0.01). CONCLUSIONS: Despite the implementation of several diagnostic procedures and significant changes concerning the surgical strategy, high success rates of primary interventions for pHPT did not change over the past three decades. High success rates also can be achieved in a teaching hospital, provided that surgery is supervised by an experienced endocrine surgeon. MIP is the treatment of choice in patients with benign sporadic pHPT and positive preoperative localization studies.

Gender-Specific Aspects of Lynch Syndrome and Familial Adenomatous Polyposis.

BACKGROUND: The most frequent hereditary colorectal cancer (CRC) syndromes are Lynch syndrome and familial adenomatous polyposis (FAP), accounting for approximately 5% of the CRC burden. Both are characterized by an autosomal dominant mode of transmission and require an individualized approach of intensified screening and prophylactic surgery. METHODS: In this review, we provide an overview of the literature regarding gene- and gender-specific aspects of Lynch syndrome and FAP. Based upon available data, a personalized approach when treating patients and families with these predisposition syndromes is increasingly warranted. RESULTS: In Lynch syndrome patients, men have a significantly higher lifetime risk and earlier age of manifestation for CRC - especially in MSH6 mutation carriers. Moreover, incidence of gastric, bladder, and urothelial cancers is much higher in males. Females with an MSH6 mutation have to be aware of a very high risk especially for endometrial, but also for ovarian cancer. In FAP families, females are more prone to papillary thyroid cancers and also to desmoid tumors. CONCLUSION: It is timely to suggest gene- and gender-based adapted screening and surgical recommendations for Lynch syndrome patients. In FAP patients, females should follow intensified screening recommendations for early detection of precursors or papillary cancer of the thyroid. Moreover, desmoid patients should primarily not be subjected to surgical resection but rather to a gender-specific conservative medical treatment.

The influence of parathyroidectomy on restless legs syndrome in patients with renal hyperparathyroidism.

BACKGROUND: Restless legs syndrome (RLS) is a common and poorly understood movement disorder that leads to unpleasant leg sensations. Although RLS can be idiopathic, secondary etiologies such as iron deficiency and renal failure are common. The aim of this prospective cohort study was to evaluate whether RLS is a common feature in patients undergoing parathyroidectomy for renal hyperparathyroidism (rHPT) and if RLS-related symptoms can be influenced by surgery. METHODS: After providing written consent, patients who underwent a parathyroidectomy for rHPT between January and November 2011 answered a validated RLS-screening-questionnaire (RLSSQ). If this was suggestive for RLS a confirming questionnaire (IRLS) was also completed on the day before surgery, on the fifth postoperative day, and again during follow-up (minimum 12 months). Perioperative parathyroid hormone and calcium levels, as well as the scores of the questionnaires were analyzed. RESULTS: Twenty-one patients (14 men, 7 women) with a mean age of 47.8 ± 3.2 years underwent total parathyroidectomy with bilateral cervical thymectomy and parathyroid autotransplantation for rHPT. The mean score of the RLSSQ of all 21 patients prior to operation was 6.1 ± 0.5. In 10 of 21 patients (47.6 %) the results of the RLSSQ were suggestive for RLS with a mean score of 8.0 ± 0.3. The consecutive scores of the IRLS in these latter patients significantly dropped from 26.6 ± 1.4 to 19.0 ± 2.2 between the preoperative and postoperative settings (p < 0.05). After a mean follow-up of 17.3 ± 3.7 months the mean scores of the RLSSQ and the IRLS were 6.1 ± 0.6 and 16.3 ± 1.8. CONCLUSIONS: rHPT may play a major role in the severity of RLS-associated symptoms in patients with renal failure. Consequently, parathyroidectomy may prove to be a valuable tool to reduce RLS-associated morbidity in affected patients. However, larger prospective trials are required to confirm the possible relation between RLS and rHPT seen in the present study

TRF1 is a stem cell marker and is essential for the generation of induced pluripotent stem cells.

TRF1 is a component of the shelterin complex that protects chromosome ends. TRF1 deficiency leads to early embryonic lethality and to severe organ atrophy when deleted in adult tissues. Here we generate a reporter mouse carrying a knock-in eGFP-TRF1 fusion allele to study the role of TRF1 in stem cell biology and tissue homeostasis. We find that eGFP-TRF1 expression in mice is maximal in known adult stem cell compartments and show that TRF1 ensures their functionality. eGFP-TRF1 is highly expressed in induced pluripotent stem cells, uncoupled from the telomere elongation associated with reprogramming. Selection of eGFP-TRF1-high induced pluripotent stem cells correlates with higher pluripotency as indicated by their ability to form teratomas and chimeras. We further show that TRF1 is necessary for both induction and maintenance of pluripotency, and that TRF1 is a direct transcriptional target of Oct3/4.

Relevance of bilateral cervical thymectomy in patients with renal hyperparathyroidism: analysis of 161 patients undergoing reoperative parathyroidectomy.

BACKGROUND: The most frequent location of ectopic or supernumerary inferior parathyroid is the thymus. Bilateral cervical thymectomy has therefore been recommended as an essential part of the initial surgery for renal hyperparathyroidism (rHPT) to avoid persistent or recurrent cervical disease. The aim of this study was to evaluate how often reoperation might have been avoidable if an appropriate cervical thymectomy had been performed during initial surgery. METHODS: A prospective database of patients with rHPT was screened for patients on permanent dialysis who underwent reoperative parathyroidectomy (PTX) between 1976 and 2010. Data were retrospectively analyzed for the performance of bilateral cervical thymectomy during previous surgeries and the presence of ectopic and/or supernumerary intrathymic parathyroid glands during reoperative PTX. RESULTS: Of 161 patients who underwent reoperative PTX, 95 had neck reexploration. Among them were 29 patients with total PTX and autotransplantation, seven with subtotal PTX (3.5 glands resected), and 59 with incomplete PTX during the initial surgery. Bilateral cervical thymectomy during the initial PTX was performed in only 12 of 95 patients (12.6 %). It was revealed to be incomplete in six of them, inheriting an intrathymic parathyroid gland during reoperative interventions. Reoperative PTX revealed intrathymic parathyroid glands in 27 of 95 patients (28.4 %). The intrathymic parathyroid glands were ectopic in 17 (63.0 %) patients and supernumerary in 8 (29.6 %). Both ectopic and supernumerary intrathymic parathyroid glands were found in two patients (7.4 %). CONCLUSIONS: The risk for persistent and recurrent disease based on intrathymic parathyroid glands is a relevant problem during initial surgery for rHPT. Thus, routine bilateral cervical thymectomy that is as complete as possible is essential during the initial PTX for rHPT.

The calcitonin levels can sometimes mislead parathyroid surgeons in patients with chronic kidney disease and renal hyperparathyroidism: report of a case.

Renal hyperparathyroidism (rHPT) as a consequence of an abnormal calcium balance is a frequent complication in patients with chronic kidney disease (CKD). However, calcium homeostasis is also regulated by calcitonin. The relevance of elevated calcitonin levels in patients with rHPT is unclear. This report presents a case of a patient with CKD and mild rHPT scheduled for thyroidectomy for a suspected medullary thyroid carcinoma (MTC) within a mononodular goiter. A hemithyroidectomy with resection of both adjacent parathyroid glands and unilateral central lymph node dissection was performed. Histopathology revealed no evidence of MTC. The rHPT, calcitonin and pentagastrin test subsequently normalized and follow-up revealed no evidence for MTC within the remaining right thyroid lobe. Elevated calcitonin levels in patients with CKD may reflect a physiological response to rHPT than rather represent MTC. The thresholds for calcitonin levels need to be better defined in affected patients to determine the optimal extent of surgical resection.