Designing and utilizing 3D-printed skin incision guides during the first Dutch bilateral hand-arm transplantation.

OBJECTIVE: To preoperatively plan skin incision in the case of the first Dutch bilateral hand-arm transplantation. BACKGROUND: A bilateral hand-arm transplantation has been performed for the first time in the Netherlands in 2019. In the context of preparation for this surgical procedure, the optimal patient-specific skin flap was determined. Skin flaps should be properly matched between donor and recipient to ensure sufficient tissue for the approximation of skin over the tendon anastomosis, adequate distal tip perfusion, and esthetics. METHODS: Preoperatively, stereophotogrammetry was obtained from the upper extremities of the patient and a volunteer with similar body physique. Skin flap dimensions were determined for each extremity, which resulted in patient-specific incision patterns. Combining this digital information yielded practical skin incision guides for both the donor and acceptor arms. Finally, the computer-aided designs were 3D printed. RESULTS: The 3D prints were convenient to utilize in both shaping the donor flaps as in preparing the acceptor extremities, taking only a few seconds during precious ischemia time. There was sufficient skin flap perfusion, and the wound-healing followed an uncomplicated course. No corrections were made to the initial skin incisions. CONCLUSIONS: Three-dimensional printed templates were successfully utilized in the first Dutch bilateral hand-arm transplantation. We believe its usage increased time efficiency, improved the match of skin flaps in donor and recipient arms, and allowed us to control the amount of skin surplus without skin flap tip necrosis. In these procedures where time is of the essence, we believe preoperative planning is imperative for its success.

The influence of variation in the P2Y12 receptor gene on in vitro platelet inhibition with the direct P2Y12 antagonist cangrelor.

Novel P2Y12 inhibitors are in development to overcome the occurrence of atherothrombotic events associated with poor responsiveness to the widely used P2Y12 inhibitor clopidogrel. Cangrelor is an intravenously administered P2Y12 inhibitor that does not need metabolic conversion to an active metabolite for its antiplatelet action, and as a consequence exhibits a more potent and consistent antiplatelet profile as compared to clopidogrel. It was the objective of this study to determine the contribution of variation in the P2Y12 receptor gene to platelet aggregation after in vitro partial P2Y12 receptor blockade with the direct antagonist cangrelor. Optical aggregometry was performed at baseline and after in vitro addition of 0.05 and 0.25 microM cangrelor to the platelet-rich plasma of 254 healthy subjects. Five haplotype-tagging (ht)-SNPs covering the entire P2Y12 receptor gene were genotyped (rs6798347C>t, rs6787801T>c, rs9859552C>a, rs6801273A>g and rs2046934T>c [T744C]) and haplotypes were inferred. The minor c allele of SNP rs6787801 was associated with a 5% lower 20 microM ADP-induced peak platelet aggregation (0.05 microM cangrelor, p<0.05). Aa homozygotes for SNP rs9859552 showed 20% and 17% less inhibition of platelet aggregation with cangrelor when compared to CC homozygotes (0.05 and 0.25 microM cangrelor respectively; p<0.05). Results of the haplotype analyses were consistent with those of the single SNPs. Polymorphisms of the P2Y12 receptor gene contribute significantly to the interindividual variability in platelet inhibition after partial in vitro blockade with the P2Y12 antagonist cangrelor.

CA 15-3 as an alternative marker for KL-6 in fibrotic lung diseases.

BACKGROUND: KL-6 is a mucin that is increased in interstitial lung diseases (ILD), and in some malignancies. CA 15-3, a tumor marker for breast cancer, refers to the same mucin but utilizes antibodies against different epitopes. OBJECTIVE: The aim of our study was to evaluate CA 15-3 as a viable alternative to KL-6 as a for ILDs with and without fibrosis. DESIGN: Serum from 242 patients with ILDs and from 327 healthy controls were included and KL-6 and CA 15-3 were measured in all subjects. Regression analyses and ROC curves were used to compare the performances of both markers. RESULTS: KL-6 and CA 15-3 levels were both significantly higher in the ILD patients compared to the controls (p < 0.0001). A weak yet significant correlation was found between serum KL-6 and CA 15-3 levels in the controls (R = 0.39, p < 0.0001), but showed a much higher correlation in the patient group (R = 0.85, p < 0.0001). CA 15-3 correlated best with KL-6 in patients with fibrotic ILDs (R = 0.83, p < 0.0001). KL-6 performed better as a marker compared to CA 15-3 in most ILDs. Both markers performed best in identifying idiopathic pulmonary fibrosis (IPF) and were equally able to differentiate between ILDs with and without fibrosis: (sensitivity and specificity %): 100/97, 95/92, and 90/72, respectively. CONCLUSION: CA 15-3 and KL-6 are equally sensitive and specific in terms of differentiating between ILDs with and without fibrosis. The wide availability, ease of use, and cost effectiveness, make CA 15-3 a viable alternative for KL-6 as a possible marker for pulmonary fibrosis.

Angiotensin II receptor type 1 1166 A/C and angiotensin converting enzyme I/D gene polymorphisms in a Dutch sarcoidosis cohort.

BACKGROUND: The angiotensin II type 1 receptor (AT2R1) is the receptor for angiotensin II, a potent vasoconstrictor produced by ACE from angiotensin I. A recent study by Biller and colleagues revealed a gender-specific association between the AT2R1 1166 A/C gene polymorphism and disease susceptibility as well as a co-dependent association between AT2R1 1166 A/C and the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism on ACE levels in a group of German sarcoidosis patients. OBJECTIVE: . The aim of our study was to compare our results from Dutch Caucasian sarcoidosis patients with the results of Biller et al. DESIGN: Serum and DNA from 99 patients with sarcoidosis and from 327 healthy controls were included. The AT2R1 1166 A/C and ACE I/D polymorphisms and serum ACE levels were analyzed in all subjects. RESULTS: No significant differences were found between the genotype distributions between the sarcoidosis patients and controls. The genotype distributions for either polymorphism between genders and between patients with progressive/chronic disease and those with acute/remission type disease were not different. The ACE D allele contributed significantly to higher ACE levels. This was true for both sarcoidosis patients and controls. There was no association between the AT2R1 1166 A/C genotype and ACE levels, nor did AT2R1 modify the ACE D/I effects on ACE levels. No significant differences were observed in co-incidence of ACE and AT2R1 genotypes between patients and controls. CONCLUSION: Our study could not confirm the findings by Biller and colleagues other than the influence of the ACE I/D polymorphism on serum ACE levels in both sarcoidosis patients and controls.

Withholding or withdrawing artificial administration of food and fluids in nursing-home patients.

BACKGROUND: withholding or withdrawing artificial administration of food and fluids, especially in incompetent patients, has been the subject of turbulent discussions. Insight into this practice may be useful in the debate, and also in the development of guidelines. OBJECTIVES: to gain insight into the frequency and circumstances of forgoing artificial administration of food and fluids in nursing homes. DESIGN: we sent a written questionnaire to the nursing-home physicians of a stratified sample of 6060 people who died in the Netherlands in 1995, and interviewed a random sample of 74 nursing-home physicians. SETTING: Dutch nursing homes. MAIN OUTCOME MEASURES: incidence of withholding or withdrawing artificial administration of food, patient characteristics and features of the decision-making process. RESULTS: in 23% of deaths in nursing homes, artificial administration of food and fluids were foregone. In two-thirds of cases, life was shortened by 1 week at most. The decision was almost always discussed with competent patients. In the case of incompetent patients, the decision was almost always discussed with the patient's relatives. Frequently mentioned considerations in the decision were: the patient's (presumed) wish, low quality of life, no prospect of improvement and the desire not unnecessarily to prolong life. CONCLUSIONS: artificial administration of food and fluids is one of the most frequently forgone treatments in nursing homes. In general, the physician involves the patient or the patient's relatives and the nursing staff in the decision-making. In most cases, the nursing-home physicians thought that the decision to forgo artificial administration of food and fluids improved the patient's quality of dying.

[Foregoing artificial feeding and hydration for nursing home patients in the last phase of life]. / Afzien van kunstmatige toediening van voeding en vocht bij verpleeghuispatiënten in de laatste levensfase.

For 3 nursing home patients in bad physical and psychiatric condition and with a poor prognosis, 2 women aged 86 and 84 years and 1 man aged 55 years, it was decided to forgo artificial feeding and hydration, after which they passed away quietly within about a week. It appears that dying in that way does not cause much suffering. Before the decision of forgoing is taken the following factors should be considered: the cause of a diminishing food and fluid intake, the severity and prognosis of underlying diseases and the (supposed) wishes of the patient. Therefore an open communication with relatives and nurses is necessary.

Synergism between cisplatin and radiotherapy in an in vitro prostate tumor cell line.

BACKGROUND: A combination of local irradiation and systemic cytotoxic treatment could improve therapeutic efficacy in metastatic prostate cancer. Radiosensitization can augment the treatment response to standard doses of radiation or enable lower treatment doses to be given; thus decreasing possible side effects. Intracellular glutathione has been implicated in the mechanism of such radio- sensitizing effects. MATERIALS AND METHODS: In the present study, R3327-MATLyLu prostate tumor cells were treated with cisplatin (0.0325 microM, 0.1625 microM, 0.325 microM and control "0 microM") in combination with irradiation (2, 4, 6, 8 Gy and control "0 Gy"). The survival of clonogenic tumor cells in agar was determined. In another experiment the irradiation was carried out after a 3 hours pretreatment with cisplatin concentrations (1.63 microM, 3.25 microM, 6.5 microM and control "0 microM") both in the presence and absence of Glutathione. RESULTS: In both experimental conditions the combination of cisplatin with irradiation yielded significant supra-additive treatment effects. CONCLUSIONS: The analysis of combination treatment effects, using two different methods confirmed the existence of synergism. The presence of a high level of extracellular glutathione did not alter the radiosensitization effects observed without glutathione, suggesting that the presence of glutathione may not be a major limiting factor in the radiosensitization effects observed in these investigations.

Response of PC-3 prostate cancer cells to combination therapy using irradiation with glucocorticoids or doxorubicin.

OBJECTIVES: We evaluated the effects of irradiation, doxorubicin and dexamethasone on human PC-3 prostate cancer cells, investigating whether dexamethasone and doxorubicin can alter the irradiation cytotoxicity of PC-3 cells. METHODS: We used the human PC-3 prostate cancer cells, analyzing cell growth with trypan blue exclusion, indices of the cell cycle with flow cytometry and apoptosis with flow cytometry and analysis of DNA fragmentation on simple agarose gel. RESULTS: Doxorubicin (100 nM) arrested cell cycle at the G2/M phase, decreased cell growth and produced apoptosis of PC-3 cells in a time-dependent manner. Dexamethasone (100 nM) increased the distribution of PC-3 cells at G0/G1 phase in the cell cycle, exerting an inhibitory effect on the proliferation of PC-3 cells after 48 and 72 hr, but it did not produce apoptosis. Irradiation (4 Gy) initially arrested cells at the G2/M phase in the cell cycle (24 hr) which was gradually overcome and the PC-3 cells were shifted into G0/G1 phase or apoptosis after 48 and 72 hr. Irradiation decreased the PC-3 cell growth by 40-50% after 48 and 72 hr, respectively. Treatment with doxorubicin (100 nM) for 24, 48, and 72 hr after irradiation potentiated irradiation cytotoxicity of PC-3 cells. Dexamethasone treatment 24 hr before and 24, 48 and 72 hr after irradiation increased the number of surviving PC-3 cells and partially neutralized the irradiation effects on cell cycle. CONCLUSION: Doxorubicin potentiated while dexamethasone partially reversed the irradiation cytotoxicity of PC-3 cells. These data may be of clinical importance for the treatment of hormone refractory prostate cancer.