Connecting the dots - A systematic review on coherence analysis in dystonia.

BACKGROUND: Increased 4-12 Hz oscillatory activity in the cortico-basal ganglia-thalamo-cortical (CBGTC) loop is reported in dystonia. Coherence analysis is a measure of linear coupling between two signals, revealing oscillatory activity drives that are common across motor units. By performing coherence analysis, activity of the CBGTC-loop can be measured with modalities like local field potentials (LFPs), electromyography (EMG), and electro-encephalography (EEG). The aim of this study is to perform a systematic review on the use of coherence analysis for clinical assessment and treatment of dystonia. METHODS: A systematic review was performed on a search in Embase and PubMed on June 28th, 2023. All studies incorporating coherence analysis and an adult dystonia cohort were included. Three authors evaluated the eligibility of the articles. Quality was assessed using the QUADAS-2 checklist. RESULTS: A total of 41 articles were included, with data of 395 adult dystonia patients. In the selected records, six different types of coherence were investigated: corticocortical, corticopallidal, corticomuscular, pallidopallidal, pallidomuscular, and intermuscular coherence. Various types of 4-12 coherence were found to be increased in all dystonia subtypes. CONCLUSION: There is increased 4-12 Hz coherence found between the cortex, basal ganglia, and affected muscles in all dystonia subtypes. However, the relationship between 4-12 Hz coherence and the dystonic clinical state has not been established. DBS treatment leads to a reduction of 4-12 Hz coherence. In combination with the results of this review, the 4-12 Hz frequency band can be used as a promising phenomenon for the development of a biomarker.

The effect of selective decontamination on the intestinal microbiota as measured with IS-pro: a taxonomic classification tool applicable for direct evaluation of intestinal microbiota in clinical routine.

Selective decontamination of the digestive tract (SDD) is aimed at elimination of potential pathogenic microorganisms. In this study, the effect of SDD on gut microbiota was evaluated in a large homogenous group of elective colorectal cancer surgery patients. Rectal swabs were taken from 118 patients undergoing colorectal surgery. These patients were randomly assigned to receive perioperative SDD or to the control group (no SDD). Rectal swabs were taken prior to surgery, 3 days after commencing administration of SDD. Gut microbial profiles were obtained with the IS-pro technique, a standardized microbiota profiling assay applicable in clinical routine. Differences in abundance for different taxonomical groups and diversity between the groups were assessed. Unsupervised and supervised classification techniques were used to assess microbial signatures, differentiating between the SDD group and the control group. Patients in the SDD group had different gut microbial signatures than in the control group, also in phyla that are not a target for SDD. Escherichia coli, Sutterella spp., Faecalibacterium prausnitzii, and Streptococcus spp. were the species that differed the most between the two groups. The SDD group showed clustering into two subgroups. In one subgroup, a decrease in Proteobacteria was observed, whereas the other subgroup showed a shift in Proteobacteria species. This study shows that SDD not only decreases colonization of the gastrointestinal tract with potential pathogenic Gram-negative microorganisms, but also reduces the abundance of normal colonizers of our gastrointestinal system and leads to a shift in total microbiota composition.

Septoplasty versus non-surgical management for nasal obstruction in adults with a deviated septum: economic evaluation alongside a randomized controlled trial.

BACKGROUND: For years, the benefits of septoplasty have been questioned. Due to the scarce and inconclusive literature, several National Health Service (NHS) Clinical Commissioning Groups in England decided to add septal surgery to their list of restricted procedures with low clinical value. Recently, evidence was obtained that septoplasty is actually more effective than non-surgical management for nasal obstruction in adults with a deviated septum. However, the relation between costs and effects of septoplasty remains unknown. METHODS: We conducted an economic evaluation alongside an open, multicenter, pragmatic randomized controlled trial in two tertiary and 16 secondary referral hospitals in the Netherlands. Adults with nasal obstruction and a deviated septum were randomized to (1) septoplasty with or without concurrent turbinate surgery or (2) non-surgical management consisting of (a combination of) medical treatment and watchful waiting. Analyses were performed on an intention-to-treat basis. Single imputation nested in the bootstrap percentile method (using 5000 bootstrap replications) was performed to assess the effect of missing data. After 12 and 24 months, we assessed the incremental costs per quality-adjusted life year (QALY) gained from a healthcare and a societal perspective. RESULTS: A total of 203 adults were randomly assigned to septoplasty (N = 102) or non-surgical management (N = 101). After 12 months, the mean cost difference between septoplasty and non-surgical management using a healthcare or societal perspective was €1181 (95%CI €1038 to €1323) or €2192 per patient (95%CI €1714 to €2670), respectively. The mean QALY difference was 0.03 per patient (95%CI - 0.01 to 0.07). Incremental costs per QALY gained from a healthcare or societal perspective were €41,763 or €77,525, respectively. After 24 months, the mean cost difference between the two groups using a healthcare or societal perspective decreased to €936 (95%CI €719 to €1153) or €1671 per patient (95%CI €952 to €2390), respectively. The mean QALY difference increased to 0.05 per patient (95%CI - 0.03 to 0.14). Incremental costs per QALY gained from a healthcare or societal perspective became €17,374 or €31,024, respectively. Analyses of imputed data did not alter our findings. CONCLUSIONS: Depending on the selected perspective, cost-effectiveness threshold, and time horizon, septoplasty has the potential to be cost-effective. Despite considerable uncertainty, septoplasty seems to be cost-effective from a healthcare perspective, after 24 months against a threshold of €20,000 per QALY. From a societal perspective, septoplasty is not yet cost-effective after 24 months, but it comes closer to the cost-effectiveness threshold as time passes by. TRIAL REGISTRATION: Nederlands Trial Register, NTR3868 (https://www.trialregister.nl/trial/3698). Prospectively registered on February 21, 2013.

Randomized clinical trial of selective decontamination of the digestive tract in elective colorectal cancer surgery (SELECT trial).

BACKGROUND: Infectious complications and anastomotic leakage affect approximately 30 per cent of patients after colorectal cancer surgery. The aim of this multicentre randomized trial was to investigate whether selective decontamination of the digestive tract (SDD) reduces these complications of elective colorectal cancer surgery. METHODS: The effectiveness of SDD was evaluated in a multicentre, open-label RCT in six centres in the Netherlands. Patients with colorectal cancer scheduled for elective curative surgery with a primary anastomosis were eligible. Oral colistin, tobramycin and amphotericin B were administered to patients in the SDD group to decontaminate the digestive tract. Both treatment and control group received intravenous cefazolin and metronidazole for perioperative prophylaxis. Mechanical bowel preparation was given for left-sided colectomies, sigmoid and anterior resections. Anastomotic leakage was the primary outcome; infectious complications and mortality were secondary outcomes. RESULTS: The outcomes for 228 patients randomized to the SDD group and 227 randomized to the control group were analysed. The trial was stopped after interim analysis demonstrated that superiority was no longer attainable. Effective SDD was confirmed by interspace DNA profiling analysis of rectal swabs. Anastomotic leakage was observed in 14 patients (6·1 per cent) in the SDD group and in 22 patients (9·7 per cent) in the control group (odds ratio (OR) 0·61, 95 per cent c.i. 0·30 to 1·22). Fewer patients in the SDD group had one or more infectious complications than patients in the control group (14·9 versus 26·9 per cent respectively; OR 0·48, 0·30 to 0·76). Multivariable analysis indicated that SDD reduced the rate of infectious complications (OR 0·47, 0·29 to 0·76). CONCLUSION: SDD reduces infectious complications after colorectal cancer resection but did not significantly reduce anastomotic leakage in this trial. Registration number: NCT01740947 ( https://www.clinicaltrials.gov).

Septoplasty for nasal obstruction due to a deviated nasal septum in adults: a systematic review.

BACKGROUND: The status of current evidence for the effectiveness of septoplasty is unclear. This systematic review evaluates the effectiveness of a) septoplasty (with or without concurrent turbinate surgery) versus non-surgical management, and b) septoplasty with concurrent turbinate surgery versus septoplasty alone, for nasal obstruction due to a deviated nasal septum in adults. METHODOLOGY: Eligible for inclusion were randomised controlled trials and non-randomised designs comparing treatment strategies. Risk of bias was assessed using Cochrane's tool. Standardised mean differences and risk differences with 95% confidence intervals were calculated. Substantial heterogeneity between included studies did not allow meta-analyses. RESULTS: No studies were found comparing septoplasty (with or without concurrent turbinate surgery) to non-surgical management, but 11 articles were included to compare septoplasty with concurrent turbinate surgery to septoplasty alone. Five studies described both subjective and objective outcomes; six studies reported one or the other. Risk of bias was overall high. Although outcomes generally improved after treatment, eight out of nine studies on subjective measures and five out of seven studies on objective measures found no additional benefit of turbinate surgery. CONCLUSIONS: Despite the routine application of septoplasty in clinical practice, the current body of evidence does not support firm conclusions on its effectiveness.

Barriers and facilitators for return to work in cancer survivors with job loss experience: a focus group study.

Over 50% of cancer survivors lose their job or quit working. Cancer survivors who experience job loss may face different challenges regarding return to work, compared to cancer survivors with employers. This qualitative study aimed to explore barriers and facilitators for return to work in cancer survivors with job loss and in insurance physicians who assist cancer survivors in their return to work. We conducted five focus groups and one interview (cancer survivors, N = 17; insurance physicians, N = 23). Topics included, among others, experience of job loss and barriers and facilitators for return to work. Data were audio recorded and analysed using thematic analysis. Our main finding was that cancer survivors experienced a double loss: loss of job on top of loss of health. As a result, cancer survivors feared for job applications, lacked opportunities to gradually increase work ability, and faced reluctance from employers in hiring them. Insurance physicians expressed a need for more frequent and longer consultations with cancer survivors with job loss. We conclude that cancer survivors who experience double loss encounter specific barriers in the return to work process. This calls for a tailored approach regarding return to work support.

Preoperative functional status is not associated with postoperative surgical complications in low risk patients undergoing esophagectomy.

Preoperative functional status is a risk factor for developing postoperative complications (POC) in major abdominal and thoracic surgery, but this has hardly been evaluated in esophageal cancer patients undergoing esophagectomy. The aim of this prospective cohort study was to determine if preoperative functional status in esophageal cancer patients is associated with POC. From March 2012 to October 2014, esophageal cancer patients scheduled for esophagectomy at the outpatient clinic of a large tertiary referral center were eligible for the study. We measured inspiratory muscle strength, hand grip strength, physical activities, and health related quality of life as indicators of functional status one day before surgery. POC were scored according to the Clavien-Dindo Classification. We used univariate and multivariate backward regression analysis to determine the association between functional status and POC. We included 94 patients in the study and esophagectomy was performed in 90 patients from which 55 developed POC (61.1%). After multivariate analysis, none of the indicators of preoperative functional status were independently associated with POC (inspiratory muscle strength [OR 1.00; P = 0.779], hand grip strength [OR 0.99; P = 0.250], physical activities [OR 1.00; P = 0.174], and health related quality of life [OR 1.02; P = 0.222]). We concluded that preoperative functional status in our study cohort is not associated with POC after esophagectomy.

Therapeutic Work as a Facilitator for Return to Paid Work in Cancer Survivors.

Purpose The increase of flexible employment in European labour markets has contributed to workers' risk of job loss. For sick-listed workers with chronic illnesses, such as cancer, and especially those without an employment contract, participation in therapeutic work may be an important step towards paid employment. The purpose of this study was to determine the role of therapeutic employment as facilitator for return to paid work, in a cohort of sick-listed cancer survivors (CSs) with and without an employment contract. Methods In this longitudinal study, data were used from a cohort of Dutch CSs (N = 192), who applied for disability benefits after 2 years of sick leave. The primary outcome measure was return to paid work after 1 year. Logistic regression analysis was applied. Results Of the participating CSs (mean age 50.7 years, 33 % male), 69 % had an employment contract at baseline. CSs without an employment contract participated significantly less in therapeutic work (p < 0.001) and were less likely to return to paid work after 1 year (p = 0.001), than those with a contract. Participation in therapeutic work significantly increased the chance of return to paid work after 1 year (OR 6.97; 95 % CI 2.94-16.51), adjusted for age, gender, level of work disability and having an employment contract. Conclusions Participation in therapeutic work could be an important facilitator for return to paid work in sick-listed CSs. The effectiveness of therapeutic work as a means to return to paid employment for sick-listed workers should be studied in an experimental setting.

Clinimetric properties of the Glasgow Health Status Inventory, Glasgow Benefit Inventory, Peak Nasal Inspiratory Flow, and 4-Phase Rhinomanometry in adults with nasal obstruction.

BACKGROUND: The validity of many measurement instruments frequently used in rhinology is unknown. This study describes clinimetric properties of well-known subjective and objective outcomes, i.e., the Glasgow Health Status Inventory, Glasgow Benefit Inventory, Peak Nasal Inspiratory Flow, and 4-Phase Rhinomanometry, in adults with nasal obstruction. METHODOLOGY: Construct validity and responsiveness were determined in 111 patients. Inter-rater and intra-rater reliability were analysed in 30 patients. We assessed content validity by interviewing patients and ENT-surgeons; construct validity by comparing hypothesised associations to calculated correlations between the outcomes; inter-rater reliability by having two researchers perform objective measurements in the same patients; intra-rater reliability by having one rater administer all instruments twice within a two-week interval; and responsiveness by comparing patients scores at baseline and three months after septoplasty or non-surgical management. RESULTS: All instruments demonstrated adequate content validity, inter-, and intra-rater reliability. Analyses of construct validity yielded low Pearsons correlations between the subjective and objective outcomes. Comparing septoplasty to non-surgical management, only the Glasgow Health Status Inventory scores were different between the two groups (mean difference 10.4, 95% CI 6.9 - 13.9). CONCLUSION: All measurement instruments scored appropriately on content validity and reliability, but only the subjective GHSI scored well on responsiveness.

Effectiveness of a tailored return to work program for cancer survivors with job loss: results of a randomized controlled trial.

BACKGROUND: Up to 53% of cancer survivors (CSs) experiences job loss during or after treatment. To support CSs with job loss in the Netherlands, a tailored return to work (RTW) program was developed. The objective of this study was to assess the effectiveness of the program on duration until sustainable RTW in CSs with job loss. MATERIAL AND METHODS: This study employed a two-armed (intervention/control) randomized controlled design with one-year follow-up. The primary outcome measure was duration until sustainable RTW. The secondary outcome measures were: rate of RTW, fatigue, quality of life, and participation in society. Descriptive analyses, Kaplan-Meier estimators and Cox regression analyses were conducted. RESULTS: Participants (N = 171) had a mean age of 48.4 years (SD = 8.6). The majority was female (69%) and breast cancer survivor (40%). The crude hazard ratio (HR) for duration until sustainable RTW was 0.86 (95% CI 0.46-1.62; p = 0.642). In the adjusted model, the intervention group had a slight, but statistically non-significant, improvement in duration until sustainable RTW compared to the control group (HR 1.16; 95% CI 0.59-2.31; p = 0.663). The program did not have any significant effects on secondary outcome measures. CONCLUSION: As the tailored RTW program did not demonstrate a statistically significant effect on duration until sustainable RTW in CSs with job loss, implementation of the program in its current form is not recommended.

Offering a tailored return to work program to cancer survivors with job loss: a process evaluation.

BACKGROUND: In Europe, 1.7 million persons of working age are diagnosed with cancer each year. During or after treatment, cancer survivors (CSs) are vulnerable for job loss, and many CSs struggle with return to work (RTW). When offering RTW interventions to CSs, it is important to conduct a process evaluation to assess such factors as the population reached and implementation problems. Recently, we developed an innovative RTW program, tailored specifically to the needs of CSs with job loss in the Netherlands. The aim of this study was to evaluate the likelihood of theory and implementation failure, as well as to evaluate procedures for recruitment, execution and implementation of the tailored RTW program for CSs with job loss. METHODS: Six components were evaluated in the RTW program: Recruitment, Reach, Dosage, Implementation, Satisfaction, and Experienced Barriers. Data were provided by logbooks and questionnaires from participating CSs, occupational health care (OHC) professionals, and re-integration coaches and job hunting officers who delivered the RTW program. SPSS and Excel were used to conduct the analyses. RESULTS: 85 CSs received the tailored RTW program. Their mean age was 47.9 years (SD 8.5). The majority were female (72 %), married (52 %), and of Dutch nationality (91 %). The program reached 88.2 % of the target population and 52 % of participants who started the program received the adequate dosage. The program implementation score was 45.9 %. Participants' mean overall program duration remained within the protocol boundaries. Re-integration coaches were more satisfied with the program than job hunting officers or OHC professionals. Likewise, participants were more satisfied with the program delivery by the re-integration coaches than with the delivery by the job hunting officers. Reported barriers within the RTW program were a lack of communication, high program intensity and short program duration, and, with regard to the job hunting officers, a lack of experience with cancer-related RTW problems. CONCLUSIONS: Participants, OHC professionals, re-integration coaches and job hunting officers generally had positive experiences with the innovative tailored RTW program. Facilitating communication between the delivering parties, and engaging usual care during program delivery, could be key elements to improved program implementation. TRIAL REGISTRATION: Dutch Trial Register, registration number NTR3562 , registered 07-08-2012.

The interrelation between microbial immunoglobulin coating, vaginal microbiota, ethnicity, and preterm birth.

BACKGROUND: Vaginal microbiota composition is associated with spontaneous preterm birth (sPTB), depending on ethnicity. Host-microbiota interactions are thought to play an important underlying role in this association between ethnicity, vaginal microbiota and sPTB. METHODS: In a prospective cohort of nulliparous pregnant women, we assessed vaginal microbiota composition, vaginal immunoglobulins (Igs), and local inflammatory markers. We performed a nested case-control study with 19 sPTB cases, matched based on ethnicity and midwifery practice to 19 term controls. RESULTS: Of the 294 included participants, 23 pregnancies ended in sPTB. We demonstrated that Lactobacillus iners-dominated microbiota, diverse microbiota, and ethnicity were all independently associated with sPTB. Microbial Ig coating was associated with both microbiota composition and ethnicity, but a direct association with sPTB was lacking. Microbial IgA and IgG coating were lowest in diverse microbiota, especially in women of any ethnic minority. When correcting for microbiota composition, increased microbial Ig coating correlated with increased inflammation. CONCLUSION: In these nulliparous pregnant women, vaginal microbiota composition is strongly associated with sPTB. Our results support that vaginal mucosal Igs might play a pivotal role in microbiota composition, microbiota-related inflammation, and vaginal community disparity within and between ethnicities. This study provides insight in host-microbe interaction, suggesting that vaginal mucosal Igs play an immunomodulatory role similar to that in the intestinal tract. Video Abstract.

Cost-effectiveness of selective decontamination of the digestive tract to decrease infectious complications in colorectal cancer surgery: An analysis of the SELECT trial.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) is effective in reducing infectious complications in elective colorectal cancer (CRC) surgery. However, it is unclear whether SDD is cost-effective compared to standard antibiotic prophylaxis. MATERIAL & METHODS: Economic evaluation alongside multicenter randomized controlled trial, the SELECT-trial, from a healthcare perspective. Patients included underwent elective surgery for non-metastatic CRC. The intervention group received oral non-absorbable colistin, tobramycin and amphotericin B (SDD) next to standard antibiotic prophylaxis. Both groups received a single shot intravenous cefazolin and metronidazole preoperatively as standard prophylaxis. Occurrence of postoperative infectious complication in the first 30 postoperative days was extracted from medical records, Quality-Adjusted Life-Years (QALYs) based on the ED-5D-3L, and healthcare costs collected from the hospital's financial administration. RESULTS: Of the 455 patients, 228 were randomly assigned to intervention group and 227 patients to the control group. SDD significantly reduced the number of infectious complications compared to control (difference = -0.13, 95 % CI -0.05 to -0.20). No difference was found for QALYs (difference = 0.002, 95 % CI -0.002 to 0.005). Healthcare costs were statistically significantly lower in the intervention group (difference = -€1258, 95 % CI -2751 to -166). The ICER was -9872 €/infectious complication prevented and -820,380 €/QALY gained. For all willingness-to-pay thresholds, the probability that prophylactic SDD was cost-effective compared to standard prophylactic practice alone was 1.0. CONCLUSION: The addition of SDD to the standard preoperative intravenous antibiotic prophylaxis is cost-effective compared to standard prophylactic practice from a healthcare perspective and should be considered as the standard of care.

Selective Decontamination with Oral Antibiotics in Colorectal Surgery: 90-day Reintervention Rates and Long-term Oncological Follow-up.

BACKGROUND: Oral antibiotics (OAB) in colorectal surgery have been shown to reduce surgical site infections (SSIs) and possibly anastomotic leakage. However, evidence on long-term follow-up, reintervention rates and 5-year oncological follow-up is lacking. The current study aims at elucidating this knowledge gap. METHODS: This study evaluated the long-term effectiveness of perioperative 'Selective decontamination of the digestive tract' (SDD) in colorectal cancer surgery. The primary outcome was anastomotic leakage within 90 days, secondary outcomes included infectious complications, reinterventions, readmission, hospital stay, and 5-year overall and disease-free-survival. Statistical analysis including univariate and multivariate analysis was performed to identify predictors of 90-day outcomes, and Kaplan-Meier survival analysis was used for the 5-year survival outcomes. RESULTS: In total 455 patients were analyzed, 228 participants in the SDD group and 227 in the control group. Anastomotic leakage rate was not statistically different between the SDD and control group (6.6% versus 9.7%). One or more infectious complications occurred in 15.4% of patients in the SDD group and in 28.2% in the control group (OR 0.46, 95% C.I. 0.29 - 0.73). In the SDD group 8,8% of patients required a reintervention compared to 16,3% of patients in the control group (OR 0.47, 95% C.I. 0.26 - 0.84). After multivariable analysis SDD remained significant in reducing both infectious complications and reinterventions after 90-days follow-up. There was no difference between SDD and control group in 5-year overall survival and disease-free-survival. CONCLUSION: SDD as OAB is effective in reducing 90-days postoperative infectious complications and reinterventions. As such, SDD as standard OAB in elective colorectal surgery is highly recommended.

Behavioral factors to modulate immunotherapy efficacy in cancer.

Immune checkpoint inhibitors, including anti-PD-1 and anti-CTLA-4 therapies, are used to (re)activate the immune system to treat cancer. Despite promising results, a large group of patients does not respond to checkpoint inhibition. In the vulnerability-stress model of behavioral medicine, behavioral factors, such as stress, exercise and classical pharmacological conditioning, predict cancer incidence, recurrence and the efficacy of conventional cancer treatments. Given the important role of the immune system in these processes, certain behavior may be promising to complement immune checkpoint inhibition therapy. Here, we discuss the preliminary evidence and suitability of three behavioral mechanisms, i.e. stress modulation, exercise and classical pharmacological conditioning for the benefit of immunotherapy. It is crucial to study the potential beneficial effects of behavioral strategies that support immunotherapeutic anti-tumor effects with rigorous experimental evidence, to exploit behavioral mechanisms in improving checkpoint inhibition efficacy.

FcalphaRI-positive liver Kupffer cells: reappraisal of the function of immunoglobulin A in immunity.

Despite the well-recognized involvement of immunoglobulin (Ig) A in mucosal immunity, the function of its receptor, FcalphaRI (CD89), is poorly understood. The ability of FcalphaRI to activate leukocytes seems to conflict with the proposed anti-inflammatory activity of secretory IgA. We show here that in a transgenic mouse model, inflammatory mediators induced expression of FcalphaRI on Kupffer cells, which enabled efficient phagocytosis in vivo of bacteria coated with serum IgA. Secretory IgA did not initiate phagocytosis. Therefore, interactions between serum IgA and FcalphaRI on Kupffer cells may provide a 'second line of defense' in mucosal immunity, by eliminating invasive bacteria entering through the portal circulation and thus preventing disease.

Familial hemophagocytic lymphohistiocytosis in a pediatric patient diagnosed by brain magnetic resonance imaging.

Familial hemophagocytic lymphohistiocytosis (fHLH) is an autosomal recessive disorder characterized by proliferation and infiltration of several organs by activated lymphocytes and macrophages. Without allogeneic stem cell transplantation, fHLH is fatal. We describe a previously healthy 11-month-old boy with a rapidly progressive encephalopathy. An older brother died at 8 months following a subacute encephalopathy diagnosed as meningoencephalitis. The family history led to the suspicion of a metabolic disease, but metabolic studies were unrevealing. MRI showed multiple inhomogeneous signal abnormalities in the cortex and white matter, most prominent in the cerebral hemispheres and around the dentate nucleus. Gadolinium-enhanced T1-weighted images showed a multitude of enhancing foci, suggestive of perivascular enhancement. Based on MRI pattern with multiple lesions, perivascular enhancement and family history, fHLH was suspected. DNA analysis showed that the patient was compound-heterozygous for the c.445 G>A (p.Gly149Ser) mutation in exon 1 and the c.757 G>A (p.Glu253Lys) mutation in exon 2 of the perforin 1 gene. The patient was treated according to the international HLH-2004 protocol (dexamethasone, etoposide, cyclosporine, intrathecal methotrexate and prednisolone) followed by allogeneic cord blood transplantation. He showed a significant neurological and radiological improvement. The reported case demonstrates that MRI pattern recognition can lead to early diagnosis of fHLH, with subsequent adequate treatment.

Low-frequency oscillation suppression in dystonia: Implications for adaptive deep brain stimulation.

BACKGROUND: Low-frequency oscillations (LFO) detected in the internal globus pallidus of dystonia patients have been identified as a physiomarker for adaptive Deep Brain Stimulation (aDBS), since LFO correlate with dystonic symptoms and are rapidly suppressed by continuous DBS (cDBS). However, it is as yet unclear how LFO should be incorporated as feedback for aDBS. OBJECTIVES: to test the acute effects of aDBS, using the amplitude of short-lived LFO-bursts to titrate stimulation, to explore the immediate effects of cDBS on LFO-modulation and dystonic symptoms, and to investigate whether a difference in the resting-state LFO is present between DBS-naïve patients and patients with chronic DBS. METHODS: seven patients were assessed during either DBS-implantation (n = 2) or battery replacement surgery (n = 5), and pseudorandomized in three conditions: no stimulation, cDBS, and aDBS. Additionally, resting-state LFP-recordings from patients undergoing battery replacement were compared to those obtained during DBS-implantation; LFP-recordings from a previous cohort of six dystonia patients undergoing DBS-implantation were incorporated into this analysis (total n = 8 newly implanted patients). RESULTS: we corroborated that a mild LFO-suppression rapidly occurs during cDBS. However, no acute changes in clinical symptoms were observed after cDBS or aDBS. Remarkably, we observed that resting-state LFO were significantly lower in patients who had been effectively treated with chronic cDBS compared to those of newly implanted patients, even when stimulation was suspended. CONCLUSIONS: our results indicate that LFO-suppression in dystonia, similar to symptom response to cDBS, might be gradual, and remain after stimulation is suspended. Therefore, tracking gradual changes in LFO may be required for aDBS implementation.

Intermuscular coherence as biomarker for pallidal deep brain stimulation efficacy in dystonia.

OBJECTIVE: Finding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients. METHODS: EEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4-12 Hz) and beta band (13-30 Hz) peak coherences were studied. RESULTS: Dystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3-10), TWSTRS: 22%, median 6.8 (IQR 4-9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit. CONCLUSIONS: Peak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity. SIGNIFICANCE: IMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice.

Veterinary advice for entrepreneurial Dutch dairy farmers: from curative practice to coach-consultant: what needs to be changed?

Dairy farms are tending to become larger, with a milk quota of more than 8 tons a year, and are managed by entrepreneurial dairy farmers with their own specific characteristics and farming style. Some Dutch veterinary practices appear unable to respond to this different style and often do not serve such farms or lose them as client. Moreover, the veterinary curriculum often focuses on traditional, family-run, smaller dairy operations and not on larger farms, which raises the question whether newly qualified veterinary practitioners are adequately trained to provide these entrepreneurial farmers with the services they require. This article addresses the characteristics of entrepreneurial dairy farmers and those of cattle practitioners, to determine whether cattle practitioners need to acquire other skills to better prepare them for their coaching-consultant tasks on larger dairy farms.