Completion thyroidectomy: effect of timing on clinical complications and oncologic outcome in patients with differentiated thyroid cancer.

BACKGROUND: Despite improved preoperative diagnostics, incidental postoperative detection of differentiated thyroid cancer in the final histology is still common. In most of these cases, completion thyroidectomy is recommended by national and international guidelines, although secondary surgery is associated with an increased operative risk. The optimal timing of completion thyroidectomy is still controversial. METHODS: Between January 1993 and December 2009, a total of 128 patients underwent completion thyroidectomy for differentiated thyroid carcinoma: papillary (n = 87) and follicular (n = 41). These patients were divided into five groups according to the time of the completion thyroidectomy after primary surgery (groups A, 1-3 days; B, 4-7 days; C, 1-7 weeks; D, 7-12 weeks; E, >3 months). Clinical complications and oncologic outcomes were analyzed. The mean follow-up was 82.5 ± 17 months. RESULTS: The overall rates of transient and persistent postoperative hypocalcemia were 7.0 and 3.1%, respectively. The rates of persistent hypocalcemia were significantly increased in groups B, C, and D in comparison to those in groups A and E (p < 0.003). The hypocalcemia rates were 7.1, 4.5, and 3.8% versus 0%, respectively. Transient or persistent vocal cord paresis was observed in eight (6.2%) and four patients (3.1%), respectively. The incidence of persistent vocal cord paresis (VCP) was significantly higher in groups B, C, and D than in groups A and E (p < 0.003). The VCP rates were 7.1, 4.5, and 3.8% versus 0%, respectively. There was no significant difference regarding survival or recurrence among the five groups. CONCLUSIONS: Considering perioperative morbidity and oncologic outcomes, completion thyroidectomy should be performed either within 3 days or beyond 3 months after primary surgery.

Health Care Workers' Sick Leave due to COVID-19 Vaccination in Context With SARS-CoV-2 Infection and Quarantine-A Multicenter Cross-Sectional Survey.

Background: Reactogenicity of coronavirus disease 2019 (COVID-19) vaccines can result in inability to work. The object of this study was to evaluate health care workers' sick leave after COVID-19 vaccination and to compare it with sick leave due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and quarantine leave. Methods: A multicenter cross-sectional survey was conducted at Regensburg University Medical Center and 10 teaching hospitals in South-East Germany from July 28 to October 15, 2021. Results: Of 2662 participants, 2309 (91.8%) were fully vaccinated without a history of SARS-CoV-2 infection. Sick leave after first/second vaccination occurred in 239 (10.4%) and 539 (23.3%) participants. In multivariable logistic regression, the adjusted odds ratio for sick leave after first/second vaccination compared with BNT162b2 was 2.26/3.72 for mRNA-1237 (95% CI, 1.28-4.01/1.99-6.96) and 27.82/0.48 for ChAdOx1-S (95% CI, 19.12-40.48/0.24-0.96). The actual median sick leave (interquartile range [IQR]) was 1 (0-2) day after any vaccination. Two hundred fifty-one participants (9.4%) reported a history of SARS-CoV-2 infection (median sick leave [IQR] 14 [10-21] days), 353 (13.3%) were quarantined at least once (median quarantine leave [IQR], 14 [10-14] days). Sick leave due to SARS-CoV-2 infection (4642 days) and quarantine leave (4710 days) accounted for 7.7 times more loss of workforce than actual sick leave after first and second vaccination (1216 days) in all fully vaccinated participants. Conclusions: Sick leave after COVID-19 vaccination is frequent and is associated with the vaccine applied. COVID-19 vaccination should reduce the much higher proportion of loss of workforce due to SARS-CoV-2 infection and quarantine.

Intestinal ischemia: current treatment concepts.

PURPOSE: Mesenteric ischemia is a condition well-known among physicians treating patients with abdominal symptoms. Even so, mortality rates have not decreased significantly over the last decades. The purpose of this article is to review current treatment concepts of acute and chronic mesenteric ischemia. RESULTS: Early diagnosis is one of the most important features that determine a patient's prognosis. Conventional angiography and multidetector computed tomography are therefore appropriate to quickly diagnose mesenteric ischemia, the latter being commonly more available. Once a patient presents with signs of peritonitis, instant laparotomy is indicated, and infarcted bowel segments need to be resected, followed by a second-look operation if necessary. If bowel necrosis is clinically not suspected, different approaches should be applied according to source and nature of mesenteric ischemia. Besides established surgical treatment concepts, more and more interventional procedures are developed and evaluated. However, superiority of these new techniques could only be shown for selected patient groups so far. In chronic mesenteric ischemia, interventional approaches seem to be an attractive alternative in patients who are in a condition too bad to undergo surgery. Patients with colonic ischemia are treated best in a conservative manner and by resolving the underlying cause, if identified. CONCLUSION: Patients with acute mesenteric ischemia are still at highest risk for a fatal course of disease. New diagnostic and therapeutic developments have not been tested in larger studies yet, neither has any of these methods led to an increased survival in studies published so far. Taken together, mesenteric ischemia requires high awareness, earliest possible diagnosis, and treatment by an experienced interdisciplinary team of gastroenterologists, radiologists, and surgeons.

Inhibition of apoptosis reduces immunogeneic potential of adenoviral-treated syngeneic liver grafts.

Effects of adenoviral therapy and reduced apoptosis on immune response were investigated in a rat liver transplantation model after prolonged ischemia-reperfusion. Liver donors were treated i.v. either with an adenoviral construct, expressing bcl-2, green-fluorescent-protein, or doxycyclin. Intrahepatic apoptosis was assessed by terminal transferase dUTP nick end labeling assay. The intrahepatic presence of CD4, CD8a, CD163, immunoglobulin (Ig)beta, tumor necrosis factor (TNF)-alpha and myeloperoxidase (MPO) was quantified by realtime polymerase chain reaction at 24 hours and seven days after transplantation. Bcl-2 expression abrogated the TNF-alpha elevation and reduced apoptosis of hepatocytes and sinusoidal endothelial cells as compared to advCMV green fluorescent protein. No effects on CD4, CD8a, CD163 and MPO expression were noticed in bcl-2 pretreated livers, whereas Igbeta was slightly enhanced compared to controls. Adenoviral infected liver grafts trigger an immune response but reduced apoptosis resulted in down-regulation of TNF-alpha. Thus, bcl-2 transfer might simultaneously reduce graft ischemia reperfusion injury and immunogenicity.

Adenoviral bcl-2 transfer improves survival and early graft function after ischemia and reperfusion in rat liver transplantation.

BACKGROUND: Primary graft dysfunction due to ischemia and reperfusion injury represents a major problem in liver transplantation. The related cell stress may induce apoptosis, which can be suppressed by bcl-2. The purpose of the study was to investigate the effect of adenoviral bcl-2 gene transfer on early graft function and survival in rat liver transplantation. METHODS: An adenoviral construct that transfers bcl-2 under the control of a tetracycline inducible promoter was generated (advTetOn bcl-2) and used with a second adenovirus that transfers the repressor protein (advCMV Rep). Forty-eight hours before explantation, donor rats were treated with advTetOn bcl-2/ advCMV Rep (n=7) and doxycyclin, with the control adenoviral construct advCMV GFP (n=8) or with doxycyclin alone (n=8). Liver transplantation was performed following 16 hours of cold storage (UW). Bcl-2 expression and intrahepatic apoptosis was assessed. Bile flow was monitored 90 min posttransplantation. The endpoint for survival was 7 days. RESULTS: Bcl-2 was expressed in hepatocytes and sinusoidal lining cells. This was associated with a significant reduction of apoptotic sinusoidal lining cells and hepatocytes after 24 hours and 7 days. Bile production was significantly higher following bcl-2 pretreatment. Furthermore, bcl-2 transfer resulted in significantly improved survival (100% vs. 50% both control groups). CONCLUSIONS: Adenoviral bcl-2 transfer results in protein expression in hepatocytes and sinusoidal lining cells resulting in early graft function and survival enhancement after prolonged ischemia and reperfusion injury. The inhibition of apoptosis in the context of liver transplantation might be a reasonable approach in the treatment of graft dysfunction.

Caspase 3 inhibition improves survival and reduces early graft injury after ischemia and reperfusion in rat liver transplantation.

BACKGROUND: Apoptosis plays a crucial role after ischemia-reperfusion in organ transplantation. It is executed by caspases and influenced by the rheostat of pro- and anti-apoptotic proteins of the bcl-2 family. This study investigated the effect of specific inhibition of caspases 3 and 7 on graft function, survival, and hepatic bcl-2 levels after liver transplantation. METHODS: Lewis rats underwent syngeneic orthotopic liver transplantation after 16 hr of cold graft storage (in University of Wisconsin solution). Livers of donor animals treated with D(OMe)E(OMe)VD(OMe)-fluoromethylketone (specific inhibitor of apoptosis executor caspases 3 and 7), and appropriate control groups, were investigated. Early graft injury was quantified by measurement of bile flow and determination of microvascular graft injury by using in vivo fluorescence microscopy. Apoptosis and its regulation were examined by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining and Western blot analysis of cell death effectors, respectively. RESULTS: After specific in vivo caspase inhibition, Western blot analysis revealed inhibition of caspase-induced cleavage of poly-ADP-ribose-polymerase. Inhibition of caspases 3 and 7 resulted in a significantly decreased number of apoptotic endothelial cells and improved microvascular perfusion. A cell protective effect was also suggested by an increase of bcl-2 levels at 7 days. Most important, specific caspase blockade resulted in improved rat survival after liver transplantation. CONCLUSION: Specific inhibition of apoptosis executor caspases effectively reduces graft ischemia-reperfusion injury and improves survival in liver transplantation. Better tissue preservation after caspase inhibition correlates with reduced apoptosis execution, improved microvascular perfusion, and bcl-2 up-regulation. Therefore, specific caspase inhibition represents a promising regimen for clinical use in liver transplantation.

Benefit of Kupffer cell modulation with glycine versus Kupffer cell depletion after liver transplantation in the rat: effects on postischemic reperfusion injury, apoptotic cell death graft regeneration and survival.

Inhibition or destruction of Kupffer cells (KC) may protect against ischemia-reperfusion (IR) induced primary graft nonfunction (PNF) in liver transplantation. Besides KC activation, PNF is characterized by microvascular perfusion failure, intrahepatic leukocyte accumulation, cell death and hepatocellular dysfunction. KCs can be inactivated by different agents including gadolinium chloride (GdCl3), methyl palmitate (MP) and glycine. The effects of three KC inactivators on IR-injury after rat liver transplantation were compared in the present study. Lewis liver donors were treated with GdCl3, MP, glycine or saline (control). Liver grafts were transplanted following 24 h storage (UW solution). KC populations and IR damage were assessed by histologic analysis, quantitative real-time polymerase chain reaction (RT-PCR) and intravital microscopy. The number of hepatic ED-1 positive macrophages was diminished after GdCl3 (114.8+/-4.4/mm2 liver tissue) and MP treatment (176.0+/-5.0), versus the glycine (263.9+/-5.5) and control (272.1+/-5.6) groups. All three treatment modalities downregulated phagocytic activity for latex particles, paralleled by reduced microvascular injury (acinar perfusion index, GdCl3: 0.75+/-0.03; MP: 0.83+/-.03; glycine: 0.84+/-0.03; 0.63+/-0.03). Quantitative RT-PCR revealed elevated myeloperoxidase mRNA after glycine versus GdCl3 and MP pretreatment (3.2- and 3.4-fold, P=0.011, respectively), without difference to controls (2.9-fold of glycine). TNFalpha-mRNA was reduced after glycine- (5.2-fold), GdCl3- (19.7-fold), MP-treatment (39.5-fold) compared with controls. However, profound prevention of intrahepatic cell death and liver graft failure was solely achieved with glycine preconditioning. Different than GdCl3 and MP, glycine modulates rather than destroys KCs. Glycine appears to preserve cell viability and to TNFalpha/leukocyte dependent organ regeneration capacity, which is related to increase graft survival following liver transplantation.