Same-day discharge (SDD) vs standard enhanced recovery after surgery (ERAS) protocols for major colorectal surgery: a systematic review.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs are well-established, resulting in improved outcomes and shorter length of hospital stay (LOS). Same-day discharge (SDD), or "hyper-ERAS", is a natural progression of ERAS. This systematic review aims to compare the safety and efficacy of SDD against conventional ERAS in colorectal surgery. METHODS: The protocol was prospectively registered in PROSPERO (394793). A systematic search was performed in major databases to identify relevant articles, and a narrative systematic review was performed. Primary outcomes were readmission rates and length of hospital stay (LOS). Secondary outcomes were operative time and blood loss, postoperative pain, morbidity, nausea or vomiting, and patient satisfaction. Risks of bias was assessed using the ROBINS-I tool. RESULTS: Thirteen studies were included, with five single-arm and eight comparative studies, of which one was a randomised controlled trial. This comprised a total of 38,854 patients (SDD: 1622; ERAS: 37,232). Of the 1622 patients on the SDD pathway, 1590 patients (98%) were successfully discharged within 24 h of surgery. While most studies had an overall low risk of bias, there was considerable variability in inclusion criteria, types of surgery or anaesthesia, and discharge criteria. SDD resulted in a significantly reduced postoperative LOS, without increasing risk of 30-day readmission. Intraoperative blood loss and postoperative morbidity rates were comparable between both groups. Operative duration was shorter in the SDD group. Patient-reported satisfaction was high in the SDD cohort. CONCLUSION: SDD protocols appear to be safe and feasible in selected patients undergoing major colorectal operations. Randomised controlled trials are necessary to further substantiate these findings.

Transanal total mesorectal excision and delayed coloanal anastomosis without stoma for low rectal cancer.

The management of low rectal cancer is a perennial challenge for colorectal surgeons. The benefits of transanal total mesorectal excision (TaTME) in low rectal cancer are to secure the distal margin and avoid surgical space constraints within the deep pelvis. However, anastomotic leak remains an important concern. We report our technique and results combining TaTME with delayed coloanal anastomosis (DCAA) without bowel diversion. First, the splenic flexure, left colon and rectum are laparoscopically mobilized to mid-rectum. TaTME is performed to complete the distal rectal mobilization, and the specimen is delivered transanally and transected. The abdominoperineal colonic pull-through is secured to the anal canal and hypertonic dressing is applied regularly in the ward. The handsewn DCAA is performed one week later. An accompanying video demonstrates this technique. Five consecutive patients with low rectal cancer underwent TaTME with DCAA. All had upfront surgical resection except one who underwent total neoadjuvant therapy. Mean operative duration, blood loss, and length of hospital stay was 290 (250-375) min, 142 (10-200) ml and 11.6 (10-14) days respectively. One patient (20%) suffered a postoperative complication of persistent urinary retention, requiring an indwelling urinary catheter on discharge. There were no cases of open conversion and no instances of anastomotic leakage. Two patients (40%) had minor low anterior resection syndrome (LARS) and one (20%) had major LARS. TaTME and DCAA without stoma are complimentary techniques that augment the minimally invasive effects of laparoscopic sphincter-sparing low rectal cancer surgery, with good perioperative outcomes.

Periventricular white matter hyperintensity burden and cognitive impairment in early Parkinson's disease.

BACKGROUND AND PURPOSE: This study quantified the total brain and periventricular white matter hyperintensity (WMH) burdens in patients with early Parkinson's disease (PD) and explored their associations with cardiovascular risk factors and cognitive performance. METHODS: A total of 175 non-demented patients with early PD who had undergone baseline brain magnetic resonance imaging were included. Comprehensive neurocognitive testing was conducted to identify PD with mild cognitive impairment (PD-MCI) and to evaluate performances in individual cognitive domains. Cardiovascular risk was expressed as a modified Framingham 10-year cardiovascular risk score (mFRS). RESULTS: A total of 53.7% of this early PD cohort fulfilled the diagnostic criteria for PD-MCI. An increase in mFRS was significantly associated with increases in the total brain WMH (P = 0.015) and periventricular WMH (P = 0.040) burden, independent of age and gender. The periventricular WMH burden was significantly associated with PD-MCI (P = 0.046) in early PD, independent of cardiovascular risk factors. Patients in the 5th quintile of periventricular WMH burden were 8.6 times more likely to have PD-MCI compared with patients in the 1st quintile of periventricular WMH burden (P = 0.004). However, total brain WMH burden was not associated with PD-MCI (P = 0.158). In individual cognitive domains, heavier periventricular WMH burden was associated with worse executive function and visuospatial function independent of cardiovascular risk factors. CONCLUSION: Periventricular WMHs are a useful imaging biomarker for cognitive impairment in early PD. Cardiovascular risk factors, although associated with periventricular WMHs, were unable to fully explain the association between periventricular WMHs and cognitive impairment in early PD.

The precarious use of charm needles susuk in treatment of low back pain by traditional medicine practitioners and its possible risk to patient safety.

A 68-year-old female presented with a 1-month history of lower back pain with right-sided radiculopathy and numbness. She was diagnosed with lumbar spondylosis and treated conservatively with analgesia and physiotherapy. Imaging showed multiple susuk, a metal alloy, in the lower back region and other regions of the body. The patient had undergone traditional medicine consultation 10 years earlier when the susuk was inserted in the lower back as talisman. The practice of the insertion of susuk is popular in rural East Malaysia and Indonesia. These foreign bodies act as possible causes of chronic inflammation and granuloma formation. In addition, the localised heighten peril upon imaging. This report suggests that the insertion of multiple susuk as talisman carries risk to safety of patients when imaging, and this practice complicates the management of musculoskeletal disorders.

No association of DNM3 with age of onset in Asian Parkinson's disease.

BACKGROUND AND PURPOSE: Genetic variability in DNM3 has been shown to modify age of onset of Parkinson's disease (PD) among LRRK2 Gly2019Ser carriers in North African Arab-Berber populations. In Asian populations, the Gly2019Ser mutation is rare or absent but two other LRRK2 variants, Gly2385Arg and Arg1628PPro, increase PD risk. We aimed to determine whether the DNM3 locus was associated with age of PD onset in both carriers and non-carriers of LRRK2 risk variants in Asians. METHODS: We analyzed the association of DNM3 rs2421947 genotypes with age of PD onset in 3645 Chinese samples, of which 369 carried at least one of two Asian LRRK2 risk variants. RESULTS: DNM3 rs2421947 genotypes were not associated with age of PD onset in Chinese samples. We observed no heterogeneity in the effect of rs2421947 between the Asian LRRK2 risk variant carriers and non-carriers. CONCLUSIONS: DNM3 rs2421947 was not associated with age of PD onset in LRRK2 risk variant carriers and non-carriers in Chinese samples. Further studies in other Asian populations will be of interest.

Non-motor symptoms in early Parkinson's disease with different motor subtypes and their associations with quality of life.

BACKGROUND AND PURPOSE: The aim of this study was to examine non-motor symptoms in different Parkinson's disease (PD) motor subtypes and their associations with quality of life (QoL). METHODS: A total of 132 patients with early PD with comprehensive motor examinations and non-motor symptom assessments were included. Motor subtypes were classified based on Stebbins' method. Non-motor symptoms were assessed by the Non-Motor Symptom Scale (NMSS) and validated by more comprehensive instruments, including the Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS). QoL was measured by the Parkinson's Disease Questionnaire-8. RESULTS: We identified 66 patients (50%) with tremor-dominant (TD) subtype, 47 (35.6%) with postural instability and gait disorder (PIGD) subtype and 19 (14.4%) with Intermediate subtype. By comparing NMSS scores, patients with the PIGD subtype had more severe sleep impairment and fatigue (domain 2 score: 5.64 vs. 2.52, P < 0.001), urinary symptoms (domain 7 score: 6.96 vs. 3.48, P = 0.005) and overall more severe non-motor symptoms (NMSS total score: 25.89 vs. 17.27, P = 0.031), compared with patients with the TD subtype. Validation using the PSQI and FSS again suggested that patients with the PIGD subtype had independently and significantly more severe sleep impairment (PSQI score: 5.57 vs. 4.29, P = 0.020) and fatigue (FSS score: 34.81 vs. 25.85, P = 0.003) compared with patients with the TD subtype. Several non-motor symptoms had significant associations with QoL, among which sleep impairment and fatigue (P < 0.0001, partial r2 = 0.273) explained the largest proportion of QoL variability in patients with PD. CONCLUSIONS: Patients with the PIGD subtype had more severe sleep impairment, fatigue and urinary disturbance compared with patients with the TD subtype. Sleep impairment and fatigue were the most important factors affecting QoL independent of motor subtypes. Prompt identification and treatment of these non-motor symptoms may improve patients' QoL.

Mood and neural correlates of excessive daytime sleepiness in Parkinson's disease.

For patients with Parkinson's disease (PD), excessive daytime sleepiness (PD-EDS) is a debilitating non-motor symptom and may be affected by mood symptoms, especially depression and anxiety. Few neuroimaging works have attempted to identify the neural features of PD-EDS, but various findings were reported. The purpose of this study was to systematically review the literature on mood and neuroimaging correlates of PD-EDS. A MEDLINE, PubMed, EMBASE, and PsycInfo search for peer-reviewed original research articles on depression, anxiety, and neuroimaging in PD-EDS identified 26 studies on depression, nine on anxiety, and eight on neuroimaging. Half of the studies reported greater depression in PD-EDS-positive patients compared with PD-EDS-negative patients. There was a significantly positive correlation between depression and PD-EDS. Limited studies on anxiety in PD-EDS suggested a weak correlation between anxiety and EDS. For depression and anxiety, the effect sizes were medium when EDS was subjectively measured, but became small when EDS was objective measured. Current neuroimaging studies generally suggested diminished neural structural and functional features (eg, brain volume, white matter integrity as indicated by fractional anisotropy, and cerebral metabolism) in patients with PD-EDS. Future studies should apply objective and subjective measures of mood symptoms and EDS and improve the neuroimaging methodology via using multimodal techniques and whole-brain analysis to provide new clues on the mood and neural correlates of PD-EDS.

Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies.

Depression, anxiety and apathy are common mood disturbances in Parkinson's disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer-reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single-photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal-limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre-processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra-nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.

The impact of non-motor symptoms on the quality of life of Parkinson's disease patients: a longitudinal study.

BACKGROUND AND PURPOSE: Non-motor symptoms (NMSs) are common amongst patients with Parkinson's disease (PD); however, little is known about their influence on the health-related quality of life (QoL) over a defined follow-up period. The study was aimed to establish the impact of NMSs on the QoL of patients with PD over a 2-year follow-up period. METHOD: A total of 227 newly referred PD patients were prospectively recruited between 2013 and 2014. The Non-Motor Symptoms Scale was used to evaluate NMSs burden whilst QoL was assessed with the Parkinson's Disease Questionnaire-39 items. Motor disabilities were assessed using the Part III (motor) Unified Parkinson's Disease Rating Scale (UPDRSm). RESULTS: The mean age was 64.37 (10.18) years; 59.9% were males and a majority (89.0%) were ethnic Chinese. Almost 65% were unemployed and 84.6% had attained no more than secondary level of education. In the univariate analysis, total NMSs burden, age, gender, subsequent visit, Hoehn and Yahr staging, disease duration and UPDRSm score were individually predictive of change in the Parkinson's Disease Questionnaire Summary Index score from baseline to follow-up visit. However, in the multivariate analysis, total NMSs burden significantly predicted the QoL scores whilst motor scores did not. Specifically, NMS domains 2 (sleep/fatigue), 3 (mood/apathy) and 5 (attention/memory) were most significantly predictive of QoL change. CONCLUSION: Unlike motor disabilities, NMSs burden, in particular sleep, mood and attention, have a significant impact on the QoL of PD patients over a 2-year follow-up period.

A new paradigm emerges from the study of de novo mutations in the context of neurodevelopmental disease.

The study of de novo point mutations (new germline mutations arising from the gametes of the parents) remained largely static until the arrival of next-generation sequencing technologies, which made both whole-exome sequencing (WES) and whole-genome sequencing (WGS) feasible in practical terms. Single nucleotide polymorphism genotyping arrays have been used to identify de novo copy-number variants in a number of common neurodevelopmental conditions such as schizophrenia and autism. By contrast, as point mutations and microlesions occurring de novo are refractory to analysis by these microarray-based methods, little was known about either their frequency or impact upon neurodevelopmental disease, until the advent of WES. De novo point mutations have recently been implicated in schizophrenia, autism and mental retardation through the WES of case-parent trios. Taken together, these findings strengthen the hypothesis that the occurrence of de novo mutations could account for the high prevalence of such diseases that are associated with a marked reduction in fecundity. De novo point mutations are also known to be responsible for many sporadic cases of rare dominant mendelian disorders such as Kabuki syndrome, Schinzel-Giedion syndrome and Bohring-Opitz syndrome. These disorders share a common feature in that they are all characterized by intellectual disability. In summary, recent WES studies of neurodevelopmental and neuropsychiatric disease have provided new insights into the role of de novo mutations in these disorders. Our knowledge of de novo mutations is likely to be further accelerated by WGS. However, the collection of case-parent trios will be a prerequisite for such studies. This review aims to discuss recent developments in the study of de novo mutations made possible by technological advances in DNA sequencing.

Clinico-genetic comparisons of paroxysmal kinesigenic dyskinesia patients with and without PRRT2 mutations.

BACKGROUND AND PURPOSE: Mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesias (PKD); however, not many detailed clinico-genetic correlations have been performed. METHODS: To investigate PRRT2 mutations in a mixed Asian PKD population and perform clinico-genetic correlations, we recruited patients between 2002 and 2011 and administered a standardized questionnaire. RESULTS: Amongst 29 unrelated patients with PKD recruited, five PRRT2 mutations were present in 15 patients. Three mutations (c.649dupC, c.649delC, c.649C>T) were previous reported, while three were novel mutations (c.604delT; c.609_611delACC/p.Ser202Hisfs; c.697_698delAG/p.Ser233Trp fsX5). Clinico-genetic correlations revealed that a history of seizures was more common in patients with PRRT2 mutations, although this did not reach statistical significance (P= 0.08). A younger age of onset, non-Chinese, and the presence of premonitory sensations were significantly associated with PRRT2 mutations in the univariate analysis. Multivariate logistic regression analysis demonstrated that age of onset [odds ratio (OR) = 0.59, P = 0.025] and premonitory sensation (OR = 10.67, P = 0.028) were independently associated with positive PRRT2 mutation. CONCLUSIONS: PRRT2 mutations are common in patients with PKD, and a double PRRT2 mutation is reported for the first time. PRRT2 mutations are significantly associated with a younger age of onset and the presence of premonitory sensation in our population.

MTHFR C677T variant reduces risk of sporadic Parkinson's disease in ethnic Chinese.

BACKGROUND: Genetic variability of methylenetetrahydrofolate reductase (MTHFR) may be associated with Parkinson's disease (PD). Its role in ethnic Chinese population is still unclear. Our study aimed to investigate whether MTHFR C677T variation was linked to PD risk in a Han Chinese population from mainland China. METHODS: To investigate the association with the risk of PD, we analyzed the single-nucleotide polymorphism C677T in MTHFR gene using a case-control methodology. A total of 1482 subjects included 765 patients with idiopathic PD, and 717 age- and sex-matched controls were recruited in this study. RESULTS: The T allele of MTHFR C677T was associated with a decreased risk of PD (OR = 0.80, 95% CI: 0.688-0.926, P = 0.003). Patients with CT + TT genotypes have a decreased risk of PD compared with those with CC genotypes (OR = 0.66, 95%CI: 0.532-0.813, P = 0.000). CT + TT subjects cannot be differentiated from CC subjects based on their clinical features. CONCLUSION: We showed that the C677T polymorphism in MTHFR gene was associated with decreased PD susceptibility in a Han Chinese population from mainland China. Efforts to fully elucidate the pathophysiologic role of the variant in PD should be necessary.

Comparison of cryopreserved amniotic membrane and umbilical cord tissue with dehydrated amniotic membrane/chorion tissue.

OBJECTIVE: To evaluate how the different processing methods cryopreservation and dehydration affect the structural integrity and biological composition of key signalling molecules within amniotic membrane and umbilical cord tissues. METHOD: We directly compared cryopreserved amniotic membrane (AM) and umbilical cord (UC) tissues with dehydrated amniotic membrane/chorion (dHACM) tissue using biochemical and functional assays including histological and histochemical staining, BCA, agarose gel electrophoresis, western blot, ELISA, and proliferation and cell death assays. RESULTS: Cryopreservation retains the native architecture of the AM/UC extracellular matrix and maintains the quantity and activity of key biological signals present in fresh AM/UC, including high molecular weight hyaluronic acid, heavy chain-HA complex, and pentraxin 3. In contrast, dehydrated tissues were structurally compromised and almost completely lacked these crucial components. CONCLUSION: The results presented here indicate that cryopreservation better preserves the structural and biological signaling molecules of foetal tissues.

Association of HLA locus variant in Parkinson's disease.

A variant (rs3129882) in the genome-wide association study (GWAS)-linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinson's disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic-specific effect or environmental agents may modulate the effect of this GWAS-linked locus in influencing the risk of PD.

Headache in hemifacial spasm patients.

OBJECTIVES: To assess prevalence of headaches in patients with hemifacial spasm. To determine whether hemifacial spasm provokes headaches and identifies predictive factors. To evaluate whether botulinum toxin given for hemifacial spasm improves headaches. METHODS: Seventy patients with hemifacial spasm were evaluated for headaches. The relationship of headaches with hemifacial spasm, impact on quality of life (HIT-6), and improvement in headaches from botulinum toxin was recorded. Data on duration, severity, and impact on quality of life (HFS-7) of hemifacial spasm were collected. RESULTS: Hemifacial spasm-related headache was significantly associated with increased hemifacial spasm severity (P < 0.001) and HIT-6 (P = 0.024). Greater hemifacial spasm severity was predictive of hemifacial spasm-related headache (P = 0.006, OR 19.1, 95% CI 2.35-155.64). Botulinum toxin (BTX) for hemifacial spasm improved hemifacial spasm-related headaches (P < 0.001). CONCLUSIONS: Hemifacial spasm can complicate headaches, particularly in patients with greater hemifacial spasm severity. Individually tailored regimens of botulinum toxin may be indicated in these patients.

MCCC1/LAMP3 reduces risk of sporadic Parkinson's disease in Han Chinese.

BACKGROUND: A recent large-scale replication and heterogeneity study reported the new described GWAS locus (MCCC1/LAMP3 rs11711441) was associated with a reduced risk of Parkinson disease (PD) in Asian and Caucasian populations. Its role is still unknown in a Han Chinese population from mainland China. We genotyped the rs11711441 variant to investigate the association with risk of PD. METHODS: Using a case-control methodology, a total of 1428 Han Chinese study subjects were genotyped. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics of GA + AA subjects with GG subjects. RESULTS: In this study, we confirmed that the A allele of MCCC1/LAMP3 (rs11711441) polymorphism reduces the risk to develop sporadic PD (P = 0.043). Additionally, subjects with GA + AA genotypes have a reduced risk compared to those with GG genotype (P = 0.022). The association was seen among the older age group (P = 0.014), but was not significant among the younger age group (P = 0.641). No significant differences were observed in gender, age at onset, and onset symptoms between GA + AA subjects and GG subjects. CONCLUSION: Our study, the first from Mainland China demonstrates that MCCC1/LAMP3 (rs11711441) is associated with a lower risk of PD. Further studies in additional Chinese populations and other cohorts will be useful.

Complementary therapies in hemifacial spasm and comparison with other movement disorders.

OBJECTIVES: We determined the prevalence, range and factors influencing the use of complementary therapy among hemifacial spasm patients and compared the patterns of use of complementary therapies across different movement disorders in a systematic pooled analysis of published literature. METHODS: A structured questionnaire was administered to 96 hemifacial spasm patients evaluating frequency of complementary therapy use, and factors influencing patients' decision to seek these therapies. We also performed a PubMed search of epidemiology studies on use of complementary therapies in movement disorders. RESULTS: Fifty-one per cent of patients had tried complementary therapies, of which 47% reported some perceived benefit and 4.1% informed their doctor. Acupuncture (71.4%) and facial massage (17.6%) were most commonly used. Complementary therapy use was associated with greater HFS severity. The mean cost of treatment was about $78 per month. We identified eight articles on use of complementary therapies in movement disorders; Parkinson's disease (5), Tourette syndrome (2) and dystonia (1). Twenty-five to 88% of patient had tried complementary therapies, of which 32-70% reported some benefit. Trials of acupuncture (2-63%) and massage (7-38%) were reported across the spectrum of movement disorders studied. Mean cost of complementary therapies varied from 43 to 102 USD per month. CONCLUSION: Complementary therapies are used by over 50% of HFS patients, and the use is correlated with severity of disease. Despite differences in race, culture and population demographics, acupuncture and massage are used by patients across the spectrum of movement disorders.

The Conundrum of Dystonia in Essential Tremor Patients: How does One Classify these Cases?

Background: The relationship between essential tremor (ET) and dystonia has been long debated and the boundaries between these disorders remain unclear. Here, we highlight the diagnostic uncertainty that can arise when observing dystonic postures in patients who have received ET diagnoses. Methods: An international panel of seven movement disorders neurologists from five countries reviewed the clinical history and videotaped neurological examinations of five individuals diagnosed with ET who also had various features of dystonia on neurological examination. Experts were instructed to assign diagnoses and provide their rationale for diagnostic assignments. Results: The five cases each exhibited a variety of abnormal postures. These were observed by all experts, and interpreted as dystonic postures by six experts. According to six of seven experts, all five cases had ET. One expert classified all cases as dystonic tremor rather than ET. One case had cervical dystonia, and five of seven experts assigned dual diagnoses of ET and dystonia in that case. The assignment of dystonia diagnoses was variable among the other four cases, with two to three experts assigning this diagnosis in each case, underscoring differences in diagnostic interpretation of dystonic postures on examination. Conclusions: This study draws attention to some of the differences between experts in assigning diagnoses of ET or dystonia to individuals with ET and abnormal postures. The goal here was not necessarily to build consensus, but to raise issues, highlight areas of uncertainty, and identify areas of common vs. differentiated thought. Several questions for additional research were also raised.