A benign congenital myopathy in an inbred Samaritan family.

We describe a novel form of myopathy in a mother and her two daughters from an inbred Samaritan family. The patients displayed severe neonatal hypotonia, lethargy and dysmorphic features. Motor milestones were delayed; however, the hypotonia and muscle weakness gradually improved during the first 2 years of life and independent walking was achieved by 18 months. The mother at the age of 23 years shows myopathic facies and minimal proximal weakness. Her intelligence is normal. Her muscle biopsy revealed central nuclei and disruption of the intermyofibrillary network with moth eaten and spiral fibers. Mutations in SMN, MTM1 and the myotonic dystrophy genes were excluded. We suggest this is a new benign form of congenital myopathy. Inheritance is probably autosomal recessive.     

A Pan-Canadian Consensus Statement on First-Line PARP Inhibitor Maintenance for Advanced,High-Grade Serous and Endometrioid Tubal,Ovarian, and Primary Peritoneal Cancers

The majority of patients with advanced, high-grade epithelial-tubo ovarian cancer (EOC) respond well to initial treatment with platinum-based chemotherapy; however, up to 80% of patients will experience a recurrence. Poly(ADP-ribose) Polymerase (PARP) inhibitors have been established as a standard of care maintenance therapy to prolong remission and prevent relapse following a response to first-line platinum-chemotherapy. Olaparib and niraparib are the PARP inhibitors currently approved for use in the first-line maintenance setting in Canada. Selection of maintenance therapy requires consideration of patient and tumour factors, presence of germline and somatic mutations, expected drug toxicity profile, and treatment access. This paper discusses the current clinical evidence for first-line PARP inhibitor maintenance therapy in patients with advanced, high-grade EOC and presents consensus statements and a treatment algorithm to aid Canadian oncologists on the selection and use of PARP inhibitors within the Canadian EOC treatment landscape.     

Repetitive milrinone therapy in ambulatory advanced heart failure patients

BackgroundAdvanced heart failure (HF) patients usually poorly tolerate guideline‐directed HF medical therapy (GDMT) and suffer high rates of morbidity and mortality. The use of continuous inotropes in the outpatient settings is hampered by previous data showing excess morbidity. We aimed to assess the safety and efficacy of repetitive, intermittent, short‐term intravenous milrinone therapy in advanced HF patients with an intention to introduce and up‐titrate GDMT and improve functional class.HypothesisRepetitive, intermittent milrinone therapy may assist with the stabilization of advanced HF patients.MethodsAdvanced HF patients treated with beta‐blockers and implanted with defibrillators were initiated with repetitive, intermittent short‐term intravenous milrinone therapy at our HF outpatient unit. Patients were prospectively followed with defibrillator interrogation, functional class assessment, B‐natriuretic peptide (BNP) levels, and echocardiography parameters.ResultsThe cohort included 24 patients with a mean 330 ± 240 days of milrinone therapy exposure. Mean age was 73 ± 6 years with male predominance (96%). Following milrinone therapy, median BNP levels decreased significantly (882 [286−3768] to 631 [278−1378] pg/ml, p = .017) with a significant reduction in the number of patients with New York Heart Association (NYHA) Class III and IV (p = .012, 0.013) and an increase in number of patients on GDMT. Importantly, the number of total sustained ventricular tachycardia events and HF hospitalizations did not change.ConclusionsIn this small cohort of advanced HF, repetitive, intermittent, short‐term milrinone therapy was found to be safe and potentially efficacious.     

Late whiplash syndrome: correlation of brain SPECT with neuropsychological tests and P300 event-related potential

BACKGROUND: The acceleration forces infringing the cervical spine in whiplash injury are frequently associated with multiple cerebral symptoms. The purpose of this study was to determine whether there is a correlation between cerebral perfusion findings, P300 recording (an electrophysiologic marker of cognitive ability), and neuropsychological tests in patients with whiplash injury. METHODS: Twenty patients with chronic whiplash injury underwent extensive clinical evaluation and neuropsychological testing. A brain single-photon emission computed tomography (SPECT) study using 99mTc-HMPAO was performed in all patients within 24 hours of neuropsychological evaluation. P300 event-related potentials were performed in 15 patients and in 9 normal volunteers. RESULTS: Thirteen of 20 patients had brain perfusion abnormalities on the SPECT studies, in one or more regions. Eight of 15 patients had abnormal P300 studies. Seven of eight patients with abnormal P300 had also an abnormal SPECT study. Seven of 15 patients had normal P300 results, 6 of them with a normal SPECT and 1 with SPECT abnormalities. There was no significant correlation between the SPECT findings or the P300 results and the scores of attention and working memory. There was, however, close agreement between the SPECT and P300. CONCLUSION: SPECT perfusion abnormalities in patients with chronic whiplash syndrome correlate well with P300 recording. The combination of these studies with neurocognitive and neurobehavioral tests may be useful in identifying a subgroup of patients having organic brain lesions.     

Perianal Crohn disease: a new scoring system to evaluate and predict outcome of surgical intervention

BACKGROUND: Conventional Crohn disease activity indices do not reflect perianal disease activity or allow prognostic implications from surgery. HYPOTHESIS: A new scoring system, based on the patient's disease history and physical examination findings, will allow more accurate use of surgical intervention for perianal Crohn disease. METHODS: A standardized scoring questionnaire was developed and applied to a consecutive group of patients before surgical treatment of perianal Crohn disease. The scoring system included abscess, fistula, ulcer and fissure, stenosis, incontinence, and concomitant disease. Weighted factors included acuity vs chronicity, de novo vs recurrent disease, and concomitant intestinal disease. The scoring system was validated against the surgical outcome, which was classified as poor, satisfactory, or good. RESULTS: Twenty-eight patients with Crohn disease who underwent 33 surgical procedures had a mean score of 16.5 (range, 3-37; possible range, 0-55). Using the Spearman nonparametric correlation test, the scoring system was accurate in predicting the outcome of surgical intervention (correlation coefficient, 0.78, 95% confidence interval, 0.57-0.89; P<.001) at mean follow-up of 20.8 months (range, 6-40 months). Correlation was further validated using a linear regression model (r = 0.75, slope best-fit value, 3.8; 95% confidence interval, 2.46-5.14; P<.001). All patients with a score of 10 or less had a good outcome, whereas all those with a score of 20 or greater had a poor outcome. CONCLUSIONS: The proposed scoring system correlated well with the short-term outcome of surgical intervention in patients with perianal Crohn disease and allowed prediction of surgical success. Ultimately, it may be possible to alter therapy based on preoperative prediction of the expected postoperative outcome.     

Citrate clearance in children receiving continuous venovenous renal replacement therapy

Anticoagulation is usually indicated in patients receiving continuous renal replacement therapy (CRRT) to prevent clotting of the extra-corporeal circuit. While heparin is the most frequently used anticoagulant, regional citrate anticoagulation is becoming the preferred choice in those patients at high risk for bleeding. However, it has been widely claimed that to avoid citrate toxicity, CRRT with citrate anticoagulation should utilize diffusive clearance (e.g., continuous venovenous hemodialysis). We studied citrate clearance in five children who received citrate anticoagulation during CRRT with a COBE PRISMA machine and an M-60 (AN-69) filter. The blood flow rate ranged from 50 to 150 ml/min (2.1-8.0 ml/kg per min). Citrate was infused in the circuit circulation as an acid citrate dextrose (ACD) solution at a rate of 1.6-3.7% of the blood flow rate to maintain the circuit ionized calcium (iCa) <0.5 mmol/l. Calcium-free replacement fluid with reduced alkali (NaHCO3 20 mEq/l) was infused in pre-filter mode at a rate of 1,800-2,000 ml/h per 1.73 m(2). In a separate central line, CaCl2 (0.8%) was infused (rate 25-50% of ACD infusion) to maintain systemic iCa between 1.0 and 1.3 mmol/l. Citrate concentration was measured using an enzymatic assay. Total CRRT duration was 1,224 h. Twenty-four filters were changed due to clotting, with a mean filter life of 51 h. Mean (range) citrate levels (mmol/l) were (1) before initiating CRRT ( n=2): patient baseline 0.13 (0.1-0.15), (2) during CRRT ( n=7): circuit 4.54 (3.95-6.25), effluent 4.31 (3.95-5.46), and patient 0.69 (0.30-1.13). Sieving coefficients for urea and citrate were 0.88-0.97 and 0.88-1.0, respectively. Citrate clearance (31-38 ml/min per 1.73 m(2)) was similar to that of urea (31-38 ml/min per 1.73 m(2)), and when evaluated in two patients, remained unchanged after substituting half of the convective clearance [continuous venovenous hemofiltration (CVVH)] by diffusive clearance [continuous venovenous hemodiafiltration (CVVHDF)]. The post-filter citrate load (mean+/-SD) delivered to the five patients during CRRT was 1.06+/-0.62 mmol/kg per hour. With the exception of alkalosis in one patient, no other complications were observed. Renal function recovered in all patients. We conclude that citrate anticoagulation in children is feasible, effective, and safe. Sufficient citrate clearance to prevent its toxic accumulation is achieved by convective clearance (CVVH) alone and diffusive clearance (CVVHDF) does not appear to be mandatory when utilizing citrate anticoagulation during CRRT.     

Sleep, sleepiness, and behavior problems in children with headache

The purpose of this study was to assess sleep, daytime sleepiness, and behavior problems in children suffering from headaches and in controls, with a special focus on the role of gender. A clinical group of 28 children with persistent headache complaints and a control group of 108 healthy children were included. Sleep was assessed by actigraphy and diaries. Behavior problems were assessed by parental reports. In comparison with the control group, the sleep quality of the clinical group was poorer and they complained more about excessive daytime sleepiness. Children suffering from headache showed higher levels of internalizing behavior problems. Gender was found to be a moderating factor for the relationships between headache and sleep. Compared with control girls, girls suffering from headaches had poorer sleep quality, whereas the opposite was true for the boys. The results highlight the importance of assessing sleep, daytime sleepiness, and psychologic adjustment in children complaining about headaches as an integral part of their routine assessment.     

Does preoperative symptom classification impact prognosis in patients with clinically localized upper-tract urothelial carcinoma managed by radical nephroureterectomy?

ObjectivesTo evaluate if preoperative symptom classification could refine prediction of outcomes for patients with clinically localized upper-tract urothelial carcinoma (UTUC) managed by radical nephroureterectomy (RNU).MethodsData on 654 patients with localized UTUC who underwent RNU were reviewed. Preoperative symptoms were classified as incidental (S1), local (S2), and systemic (S3). Clinical and pathologic data were compared between the cohorts. Kaplan-Meier analyses and Cox proportional hazard modeling were used to determine recurrence-free and cancer-specific survival amongst the symptom cohorts.ResultsSymptom classification was S1 in 213 (33%) patients, S2 in 402 (61%), and S3 in 39 (6%). S3 symptoms were associated with advanced pathology, including higher stage, grade, and lymph node (LN) positivity. Five and 10-year recurrence-free and cancer-specific survival estimates were similar for patients with S1 and S2 symptoms (P = 0.75 and 0.58, respectively), but was worse for patients with S3 symptoms (P < 0.001 for both). On multivariate analysis adjusting for final pathologic stage, grade, and LN status, S3 symptoms were not an independent predictor of recurrence (HR 1.44, P = 0.19) or death due to disease (HR 1.66, P = 0.07). Addition of symptom classification, however, increased the accuracy of a model consisting of stage, grade, and LNs for prediction of recurrence-free and cancer-specific survival by 1.4% and 1.3%, respectively (P < 0.001 for both).ConclusionsLocal symptoms do not confer worse prognosis compared with patients with incidentally detected UTUC. However, systemic symptoms are associated with worse outcomes despite apparently effective RNU. Patients with systemic symptoms may harbor micrometastatic disease and could potentially benefit from a more rigorous metastatic evaluation or perioperative chemotherapy regimens.