Impaired coenzyme A homeostasis in cardiac dysfunction and benefits of boosting coenzyme A production with vitamin B5 and its derivatives in the management of heart failure.

Coenzyme A (CoA) is an essential cofactor required for over a hundred metabolic reactions in the human body. This cofactor is synthesized de novo in our cells from vitamin B5, also known as pantothenic acid, a water-soluble vitamin abundantly present in vegetables and animal-based foods. Neurodegenerative disorders, cancer, and infectious diseases have been linked to defects in de novo CoA biosynthesis or reduced levels of this coenzyme. There is now accumulating evidence that CoA limitation is a critical pathomechanism in cardiac dysfunction too. In the current review, we will summarize our current knowledge on CoA and heart failure, with emphasis on two primary cardiomyopathies, phosphopantothenoylcysteine synthetase and phosphopantothenoylcysteine decarboxylase deficiency disorders biochemically characterized by a decreased level of CoA in patients' samples. Hence, we will discuss the potential benefits of CoA restoration in these diseases and, more generally, in heart failure, by vitamin B5 and its derivatives pantethine and 4'-phosphopantetheine.

A comparison of the Thunderbeat and standard electrocautery devices in head and neck surgery: a prospective randomized controlled trial.

PURPOSE: New energy-based sutureless vessel ligation devices, such as the Thunderbeat (Olympus Medical Systems Corp., Tokyo, Japan), could reduce operative time and limit blood loss in head and neck surgery; however, efficacy and safety in major head and neck surgery have not been investigated in a prospective, randomized study. METHODS: This prospective, double-arm, randomized controlled trial consisted of two parts: total laryngectomy (TL) and neck dissection (ND). Thirty patients planned for TL were randomized in two groups. For the ND part, forty-two operative sides were likewise randomized. In both parts, Thunderbeat was used in addition to the standard instrumentation in the intervention groups, while only standard instrumentation was used in the control groups. Primary outcome values were blood loss, operative time and complication rate. RESULTS: For the TL part there was no difference in mean blood loss (p = 0.062), operative time (p = 0.512) and complications (p = 0.662) between both hemostatic techniques. For the neck dissection part, there was a reduction in blood loss (mean 210 mL versus 431 mL, p = 0.046) and in operative time (median 101 (IQR 85-130) minutes versus 150 (IQR 130-199) minutes, p = 0.014) when Thunderbeat was used. There was no difference in complication rate between both hemostatic systems (p = 0.261). CONCLUSION: The Thunderbeat hemostatic device significantly reduces operative blood loss and operative time for neck dissections, without increase in complications. In TL, blood loss using Thunderbeat was comparable with the standard technique, but the operative time tended to be shorter. TRIAL REGISTRATION: UMCG Research Register, Reg. no. 201700041, date of registration: 18/1/2017.

Cervical Stabilization in Patients with Instability Resulting from Osteoradionecrosis with Subsequent Spondylodiscitis After Radiotherapeutic Treatment for Head- and Neck Carcinoma.

High dose of radiation to bone may cause necrosis. Osteoradionecrosis of the cervical vertebrae is a rare adverse event of radiotherapy in patients treated for head and neck cancer. The risk on osteoradionecrosis will increase with doses exceeding 60 Gy. Minimal trauma of the overlying mucosa of the heavily irradiated cervical spine causes subsequent infections or instability may cause neck pain and severe neurological disability. In four patients the cervical spine received up to 100 Gy due to reirradiation. Clinically the patients presented with neck pain. All patients had defects in the pharyngeal posterior wall and cervical instability due to osteoradionecrosis of several cervical vertebrae. Despite optimal conservative treatment the patients developed sensory and motor function loss of the upper extremities. Laminectomies were performed and the cervical spine was stabilized. The pharyngeal posterior wall defects could not be reconstructed. All patients received lifelong antibiotic treatment. Pain and neurological deficits declined after surgery and initiating antibiotics. Eventually all patients could take up their daily activities. Three patients died between 6 months and 2 years after surgery. The cause of death was not related to the osteoradionecrosis. In case of cervical osteoradionecrosis, with secondary infections, stability of the spine should be restored even when the integrity of the pharyngeal posterior wall cannot be restored. Our cases demonstrate that even when an anterior approach is impossible, due to irradiation changed tissue structures of the pharyngeal posterior wall, a combination of lifelong antibiotic treatment and posterior stabilization is a good alternative. The vertebrae affected by osteoradionecrosis and secondary infection can be left in situ. This intervention leads to improvement in quality of life.

Short- and long-term complications of surgical and percutaneous dilatation tracheotomies: a large single-centre retrospective cohort study.

OBJECTIVES: The aim of this study was to determine and compare the incidence of long- and short-term complications of percutaneous dilatation tracheotomies (PDT) and surgical tracheotomies (ST). DESIGN: A single-centre retrospective study. PARTICIPANTS: 305 patients undergoing a tracheotomy (PDT or ST) in the University Medical Center Groningen from 2003 to 2013 were included. Data were gathered from patient files. MAIN OUTCOME MEASURES: Short-term and long-term complications including tracheal stenosis. RESULTS: The incidence of short- and long-term complications, including tracheal stenosis, was similar in both groups. Analysis of a small high-risk subgroup showed no difference in long-term complications. CONCLUSIONS: The rate of short- and long-term complications, including tracheal stenosis, is equal in PDT and ST. PDT is a safe alternative for ST in selected patients.

Clinical feasibility study of protrach dualcare a new speaking valve with heat and moisture exchanger for tracheotomized patients.

Objective: The aim of this study was to evaluate the clinical feasibility of the ProTrach DualCare (Atos Medical, Hörby, Sweden), a device combining a hands-free speaking valve and a Heat and Moisture Exchanger (HME) for tracheotomized patients. Study Design: A non-randomized, prospective single center feasibility study. Methods: Sixteen adult tracheotomized patients were included. Participants were asked to test the DualCare for two weeks while continuing their normal activities. After these two weeks, participants could choose whether or not to take part in the long-term evaluation. The EuroQOL-5D, Borg scale and questionnaires on speaking, pulmonary function and patient preference were used. During the long-term evaluation, a minor redesign was implemented and all participants were asked to test the new device again for one week, with a potential long-term evaluation. Eleven decided to participate. Results: The device was well-tolerated. Speaking noise was reduced (p = 0.020) and speech was considered to sound more natural compared to previously used devices according to the users (p = 0.020). Overall 11 participants preferred the DualCare to their standard device. No serious adverse events were reported. Conclusion: Overall, 11 of 16 participants preferred the DualCare to their standard speaking valve or HME. Users of the DualCare were able to use hands free speech with the benefits of an HME and the device was considered clinically feasible and has the potential to improve quality of life of tracheotomized patients. Level of Evidence: 2b.

Early feeding after total laryngectomy results in shorter hospital stay without increased risk of complications: a retrospective case-control study.

OBJECTIVES: To evaluate the effects of a reduced nil per os (NPO) period after total laryngectomy (TLE) on general and wound-related post-operative complications, swallowing function and duration of hospital stay. DESIGN, SETTING AND PARTICIPANTS: In a retrospective case-control study in 71 patients after TLE with primary closure (i e. without reconstruction with tissue transfer), complications and hospitalisation in 36 patients who started oral feeding on days 3-5 (early feeding) were compared with 30 patients who started oral feeding on days 7-10 (late feeding). MAIN OUTCOME MEASURES: Incidence of complications, swallowing function and duration of hospitalisation. RESULTS: There were no significant differences between the early- and late-feeding groups in the occurrence of pharyngocutaneous fistulae, neopharyngeal stenosis or wound complications in general. Swallowing function was comparable for both groups. Mean overall hospitalisation was 2 days shorter in the early-feeding group (mean: 17.4 days) as compared to the late-feeding group (mean: 19.4 days) (P < 0.05). CONCLUSIONS: Early feeding after TLE without flap reconstruction did not contribute to an increase in complications and led to a shorter hospital stay.

Predictive value of the Groningen Frailty Indicator for treatment outcomes in elderly patients after head and neck, or skin cancer surgery in a retrospective cohort.

OBJECTIVES: Careful selection of patients eligible for extensive head and neck cancer surgery is extremely important. A reliable predictor for postoperative outcomes in the vulnerable elderly population is not yet available. The concept of frailty describes a clinical state of increased vulnerability and can be assessed using frailty tests, such as the Groningen Frailty Indicator. In the current study, the influence of Groningen Frailty Indicator-measured frailty on clinical outcome was investigated in elderly patients surgically treated for head and neck cancer. DESIGN: Retrospective, explorative cohort study. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 90 patients of 65 years and older receiving surgical treatment for head and neck cancer with different primary sites. MAIN OUTCOME MEASURES: The influence of frailty (Groningen Frailty Indicator) on postoperative complications (Clavien-Dindo classification), subjective postoperative experience of both patient and surgeon and survival were analysed. RESULTS: A total of 36 patients were considered as frail (40%). Postoperative complications could not be predicted by frailty status. However, the Groningen Frailty Indicator dimension 'health problems' was a significant predictor for postoperative complications (P = 0.020). Unlike age and comorbidity, frailty was associated with a poor subjective patients' experience of the postoperative recovery (P < 0.01). Although not statistically significant, survival analysis showed a worse 5-year overall survival in the frail group (33%) versus the non-frail group (74%). CONCLUSIONS: Analysis of frailty could identify elderly patients who might suffer more than expected during the postoperative period after head and neck cancer surgery. In this study, frailty was not identified as a new predictor of complications after head and neck cancer surgery.

Visualization of small glottic laryngeal cancer using methyl-labeled 11C-methionine positron emission tomography.

Despite abundant literature on the use of PET in head and neck cancer, a little is known about the visualization of small laryngeal cancer. Moreover, most literature deals with the radiopharmaceutical (18)F-fludeoxyglucose (FDG), whereas only a few papers address the use of (11)C labeled amino acids. This study was performed to evaluate the feasibility of (11)C-labeled methionine in visualizing small laryngeal cancer. Ten patients with a de novo small laryngeal cancer (7 T1, 3 T2) underwent a MET PET at least 3 weeks after biopsy but prior to further treatment. Static scans were made in 'whole body' mode, covering the head from the external auditory meatus downwards to the whole thorax. The resulting images were judged by experienced specialists in nuclear medicine, who assessed the relative visibility of each tumor on a 3-point scale. Nine tumors were visualized (5 clearly, 4 moderately). One (T1) was not visualized. Small laryngeal cancer can be visualized with (11)C-methionine PET.

Voice results in patients with T1a glottic cancer treated by radiotherapy or endoscopic measures.

Early squamous cell carcinomas of the glottis can be treated effectively by means of surgery or external beam radiotherapy. The curability rate is about the same for both treatment modalities, but differing results have been reported regarding functional results. We selected 24 patients from a larger group of patients who had been treated for T1a glottic laryngeal cancer without the involvement of the anterior commissure. Fifteen patients were treated endoscopically and nine by radiotherapy. During a routine control videolaryngostroboscopy at an outpatient clinic, an objective and a subjective voice analysis were performed. The objective and subjective voice analyses showed no differences between the two treatment modalities. Videolaryngostroboscopy showed a significantly more pronounced glottic wave at the side that was originally affected by the tumour in the radiotherapy group. This difference disappeared when we looked at both vocal cords. Significant differences between the two treatment modalities were not found in any of the other parameters. Thus, this study shows no difference in the voice quality of patients treated by irradiation or by endoscopy. Therefore, the post-treatment voice quality is not a reason to favour radiotherapy for small T1a glottic squamous cell cancers without involvement of the anterior commissure.

Value of resection of pulmonary metastases in head and neck cancer patients.

BACKGROUND: Literature shows no data about a complete cohort of head and neck cancer patients who developed pulmonary metastases. In this study, we investigate factors related to survival, with emphasis on the role of a pulmonary metastasectomy. METHODS: A retrospective review of 138 patients who developed pulmonary metastases (5.5% of all head and neck cancer patients) in the period 1978 to 1994 is presented. In a stepwise regression analysis (Cox), factors were identified related to survival. Also investigated was whether the prognostic value of potential prognosticators differed between the group that underwent metastasectomy and the group that did not. RESULTS: One hundred thirty-eight patients had metastases originating from head and neck cancer. The 5-year survival rate for all these patients was 13%. Younger patients (P = .011), patients with a longer disease-free interval (DFI) (P = .011), patients with a longer disease-free interval (DFI) (P = .016), and patients with a nonsquamous cell carcinoma (P = .038) did better. No evidence of a relationship between survival and sex or survival and number of metastases was found. Twenty-one patients underwent surgical resection of their pulmonary metastases. In 18 patients the resection was complete. The 5-year survival rate for patients who underwent a metastasectomy was 59%, compared with 4% in the nonmetastasectomy group (P = .0033). CONCLUSION: Isolated pulmonary metastases from head and neck cancer are potentially curable by surgical resection. Preconditions for this approach are locoregional control of the primary lesion and technical resectability of the pulmonary metastases. Patients with a long interval between primary treatment and the diagnosis of pulmonary metastases may benefit more from resection therapy.