Targeted amplification-based whole genome sequencing of Monkeypox virus in clinical specimens.

IMPORTANCE: We present a protocol to efficiently sequence genomes of the MPXV-causing mpox. This enables researchers and public health agencies to acquire high-quality genomic data using a rapid and cost-effective approach. Genomic data can be used to conduct surveillance and investigate mpox outbreaks. We present 91 mpox genomes that show the diversity of the 2022 mpox outbreak in Ontario, Canada.

Neonatal surgical outcomes: a prospective observational study at a Tertiary Academic Hospital in Johannesburg, South Africa.

PURPOSE: The neonatal period is the most vulnerable period for a child. There is a paucity of data on the burden of neonatal surgical disease in our setting. The aim of this study was to describe the frequency with which index neonatal surgical conditions are seen within our setting and to document the 30-day outcome of these patients. METHODS: This was a single-centre prospective observational study in which all neonates with paediatric surgical pathology referred to the paediatric surgical unit with a corrected gestational age of 28 days were included. RESULTS: Necrotising enterocolitis was the most frequent reason for referral to the paediatric surgical unit (n = 68, 34.34%). Gastroschisis was the most frequent congenital anomaly referred (n = 20, 10.10%). The overall morbidity was 57.58%. Surgical complications contributed to 18.51% of morbidities. The development of gram negative nosocomial sepsis was the most frequent cause of morbidity (n = 98, 50.78%). Mortality at 30 days was 21.74% (n = 40). Sepsis contributed to mortality in 35 patients (87.5%), 16 of which had gram negative sepsis. CONCLUSION: Gram-negative sepsis was a major contributing factor in the development of morbidity and mortality in our cohort. Prevention and improvement in infection control are imperative if we are to improve outcomes in our surgical neonates.

Improvements in Clinical Outcomes in Children with Cystic Fibrosis aged Six and 16 years.

Aims Our aim was to assess if outcomes for cystic fibrosis (CF) patients at six & sixteen years of age have improved in the last 17 years looking at FEV1, BMI and death. Methods A retrospective observational study using a prospectively maintained database of CF patients at Cork University Hospital. Results 84 patients were included in the 16-year-old data and 89 patients were included in the six-year-old data. The mean FEV1 and BMI (16 years) for the 2002-2007 group was 72.9±21.0% and 18.9±2.53 respectively, 2008-2013 group was 75.4±27.2% and 19.8±2.7 and for the 2014-2018 group was 95.2±16.0% and 22.9±4.1. The percentage of patients (16 years) with chronic pseudomonas status was 37.9% (11/30) in the 2002-2007 group, 51.6 % (16/31) in the 2008-2013 group and 4.2% (1/24) in the 2014-2018 group. The relationship between FEV1 and FVC with BMI remained significant in multivariate analysis (P <0.001). The mean FEV1 (six years) for the 2002-2007 group was 90.7±16.1%, 2008-2013 group was 99.3±17.9% and for the 2014-2018 group was 100.9±15.8%. Conclusions Improvements in FEV1 and BMI aged six and 16 years are notable as well as a significant decline in the number of patients with chronic pseudomonas.

Comparison of combination l-asparaginase plus CHOP or modified MOPP treatment protocols in dogs with multi-centric T-cell or hypercalcaemic lymphoma.

OBJECTIVES: To compare the progression-free survival of dogs with high-grade T-cell lymphoma treated with either a cyclophosphamide, doxorubicin, vincristine and prednisone-based or a modified mechlorethamine, vincristine, prednisone and procarbazine chemotherapy protocol. MATERIALS AND METHODS: In this retrospective study, cases were selected based on histologic or cytologic diagnosis of lymphoma, T-cell phenotype, hypercalcaemia, or both, and no previous chemotherapy for lymphoma. Treatment was not randomly allocated. RESULTS: Seventy-three dogs were included in this study: 50 in the cyclophosphamide, doxorubicin, vincristine and prednisone group and 23 in the mechlorethamine, vincristine, prednisone and procarbazine group. The median progression-free survival was 133 days for dogs in the cyclophosphamide, doxorubicin, vincristine and prednisone group and 97 days for dogs in the mechlorethamine, vincristine, prednisone and procarbazine group. When golden retrievers (n = 16) were evaluated -separately, progression-free survival was longer in the cyclophosphamide, doxorubicin, vincristine and prednisone versus mechlorethamine, vincristine, prednisone and procarbazine treatment group (median PFS 154 days versus 70.5 days, respectively). CLINICAL SIGNIFICANCE: The progression-free survival time for dogs with multi-centric T-cell lymphoma treated with a modified mechlorethamine, vincristine, prednisone and procarbazine protocol was similar to that of dogs treated with cyclophosphamide, doxorubicin, vincristine and prednisone. Further studies, including those evaluating golden retrievers separately, are needed to confirm these findings.

The addition of metronomic chemotherapy does not improve outcome for canine splenic haemangiosarcoma.

OBJECTIVES: To determine whether the addition of metronomic chemotherapy improved outcome for dogs with splenic haemangiosarcoma treated with splenectomy and adjuvant maximum tolerated dose chemotherapy. MATERIALS AND METHODS: Medical records were examined retrospectively for dogs with splenic haemangiosarcoma that had undergone splenectomy followed by anthracycline-based chemotherapy. Thirty-nine dogs underwent splenectomy followed by maximum tolerated dose chemotherapy with an anthracycline, cyclophosphamide, or both (Group 1). Twenty-two dogs underwent splenectomy followed by adjuvant maximum tolerated dose chemotherapy with an anthracycline, cyclophosphamide, or both, plus metronomic chemotherapy (Group 2). Dogs in both groups were further separated into those treated with either maximum tolerated dose anthracycline or maximum tolerated dose anthracycline and cyclophosphamide. RESULTS: Median progression-free survival was 165 days and median overall survival time was 180 days in Group 1. Median progression-free survival was 185 days and median overall survival time was 212 days in Group 2. In both groups, the overall survival was shorter in dogs that had received maximum tolerated dose cyclophosphamide. CLINICAL SIGNIFICANCE: The addition of metronomic to maximum tolerated dose chemotherapy protocols does not appear to improve outcome in dogs with splenic haemangiosarcoma treated with splenectomy and maximum tolerated dose chemotherapy.

Overnight sleep duration and obesity in 2-5 year-old American Indian children.

BACKGROUND: Sleep has emerged as a potentially modifiable risk factor for obesity in children. OBJECTIVES: The purpose of this investigation was to evaluate the association between overnight sleep duration and obesity among American Indian (AI) children ages 2-5 years. METHODS: Data were examined from the baseline assessment of children enrolling in the Healthy Children, Strong Families study, which is a randomized lifestyle intervention trial in five diverse rural and urban AI communities nationally among children ages 2-5 years. Multivariable models were built to assess the relationship between sleep duration and BMI z-score while controlling for potential sociodemographic and behavioural covariates. RESULTS: Three hundred and ninety-eight children had sufficient data to be included in analysis. In multivariable models controlling for potential covariates, overnight sleep duration was significantly and inversely associated with BMI z-score (B = -0.158, t = -1.774, P = 0.006). Similarly, when controlling for covariates, children who slept 12 or more hours had significantly lower BMI z-scores compared with those who slept 8 to 10 h (P = 0.018) or less than 8 h (P = 0.035); the difference between 12+ hours and 10 to 12-h groups did not reach statistical significance (P = 0.073) but supported a linear relationship between overnight sleep duration and BMI. Weekday-to-weekend variability in overnight sleep duration was not associated with BMI z-score (B = 0.010, t = 0.206, P = 0.837). CONCLUSIONS: Overnight sleep duration is independently and inversely related to BMI z-score among AI children ages 2-5 years, even when controlling for important sociodemographic and obesogenic lifestyle factors. This represents the first report, to our knowledge, of sleep duration as a risk factor for obesity among AI children.

The continued rise of Lyme disease in Ontario, Canada: 2017.

BACKGROUND: Lyme disease is an infection caused by the spirochete Borrelia burgdorferi and, in most of North America, is transmitted by the blacklegged tick Ixodes scapularis. Climate change has contributed to the expansion of the geographic range of blacklegged ticks in Ontario, increasing the risk of Lyme disease for Ontarians. OBJECTIVE: To identify the number of cases and incidence rates, as well as the geographic, seasonal and demographic distribution of Lyme disease cases reported in Ontario in 2017, with comparisons to historical trends. METHODS: Data for confirmed and probable Lyme disease cases with episode dates from January 1, 2012, through December 31, 2017, were extracted from the integrated Public Health Information System (iPHIS). Data included public health unit (PHU) of residence, episode date, age and sex. Population data from Statistics Canada were used to calculate provincial and PHU-specific incidence rates per 100,000 population. The number of cases reported in 2017 by PHU of residence, month of occurrence, age and sex was compared to the 5-year averages for the period 2012-2016. RESULTS: There were 959 probable and confirmed cases of Lyme disease reported in Ontario in 2017. This was three times higher than the 5-year (2012-2016) average of 313. The provincial incidence rate for 2017 was 6.7 cases per 100,000 population, although this varied markedly by PHU. The highest incidence rates were found in Leeds-Grenville and Lanark District (128.8 cases per 100,000), Kingston-Frontenac, Lennox and Addington (87.2 cases per 100,000), Hastings and Prince Edward Counties (28.6 cases per 100,000), Ottawa (18.1 cases per 100,000) and Eastern Ontario (13.5 cases per 100,000). Cases occurred mostly from June through September, were most common among males, and those aged 5-14 and 50-69 years. CONCLUSION: In 2017, Lyme disease incidence showed a marked increase in Ontario, especially in the eastern part of the province. If current weather and climate trends continue, blacklegged ticks carrying tick-borne pathogens, such as those causing Lyme disease, will continue to spread into suitable habitat. Monitoring the extent of this geographic spread will inform future clinical and public health actions to detect and mitigate the impact of Lyme disease in Ontario.

Risk factors for KPC-producing Enterobacteriaceae acquisition and infection in a healthcare setting with possible local transmission: a case-control study.

BACKGROUND: Reports of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) in Australia were previously uncommon, with cases imported sporadically by travellers from higher prevalence countries. AIM: The study institution reported the first outbreak of KPC-Kp in Australia. The aim of this study was to identify risk factors for KPC-Kp colonization and infection using a matched case-control study. METHODS: The study included all hospitalized patients with KPC-Kp colonization or infection from January 2012 to September 2015. FINDINGS: Thirty-four cases of KPC-producing Enterobacteriaceae (including 31 KPC-Kp cases) were matched with 136 controls. Variables associated with KPC-Kp acquisition included: length of hospital stay >28 days in the past 12 months, prior vancomycin-resistant enterococci (VRE) colonization, central venous catheter (CVC), gastrointestinal disease and invasive procedures. Exposure to broad-spectrum antibiotics was also found to be a significant risk factor. In the multi-variate analysis, three factors independently associated with KPC-Kp acquisition were length of hospital stay >28 days in the past 12 months [odds ratio (OR) 23.6, 95% confidence interval (CI) 4.9-113.3], presence of a CVC (OR 15.4, 95% CI 2.7-86.9), and prior VRE colonization (OR 6.0, 95% CI 1.6-23.2). Very few patients had a history of overseas travel. CONCLUSION: This study demonstrates that patients with prolonged hospital exposure are more likely to acquire KPC-Kp in the setting of a local outbreak, and suggests that risk factors for KPC-Kp acquisition may be shared with those for VRE colonization. Local screening strategies targeting overseas travellers would likely miss many cases. The results of this study will help to inform screening policies for carbapenemase-producing Enterobacteriaceae.

Variable phenotypes in Greig cephalopolysyndactyly sydrome (GCPS) and their relevance to plastic surgery.

BACKGROUND: Greig cephalopolysyndactyly syndrome (GCPS) is an uncommon entity characterised by polysyndactyly and craniofacial features. The syndrome is not defined by classic signs. Instead there is a high variability in phenotypes observed. This is due to the large number of different mutations in the glioma-associated oncogene 3 (GLI3) that can give rise to the syndrome. We present a case series of five un-related individuals with GCPS treated in our hand surgery unit with different phenotype presentations of GCPS. CONCLUSION: An awareness of the diversity in phenotypes is important for diagnosis and early referral for genetic confirmation and counselling.

Congenital Arteriovenous Malformation of the Forearm and Hand.

We report the case of an asymptomatic arteriovenous malformation (AVM), extending from the forearm into the palm, in an 11-year-old boy. A debulking procedure was performed meticulously dissecting the lesion from the involved structures. The post-operative course was uncomplicated and no evidence of recurrence was noted at eighteen months follow-up. Extensive AVMs involving structures vital for hand function may be asymptomatic. Clinical follow-up is paramount, due to the inherent risk of recurrence.

Managing a nosocomial outbreak of carbapenem-resistant Klebsiella pneumoniae: an early Australian hospital experience.

BACKGROUND: Carbapenems are traditionally reserved as the last line of defence for treatment of serious infections with multiresistant Gram-negative bacilli. Reports of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms have been emerging globally, but rare in Australasia to date. We describe an outbreak of KPC-2 producing K. pneumoniae at an Australian hospital. METHODS: After initial detection in October 2012, a retrospective review of patients with meropenem-resistant K. pneumoniae to June 2012, and ongoing prospective surveillance, was undertaken. Included patients were admitted to the hospital after June 2012 and had meropenem-resistant K. pneumoniae isolated from any site. Available isolates underwent detection of the KPC-2 gene by polymerase chain reaction and molecular typing was performed to determine genetic relatedness between isolates. Point-prevalence screening was performed on selected wards to detect asymptomatic carriage. Infection control procedures were implemented to contain the outbreak. RESULTS: Ten cases were identified in the initial cluster. Eight were localised to a single inpatient ward. Point-prevalence screening revealed one extra case. After temporary containment, re-emergence of KPC-producing isolates was observed post October 2013 with 18 further cases identified. Four K. pneumoniae isolates in the 2012 cluster and 16 from the 2013-2014 cluster were referred for further testing. All carried the KPC-2 beta-lactamase gene. The 2012 isolates were genetically similar to the 2014 isolates. CONCLUSION: KPC-2 mediated resistance is an emerging threat in Australia. The re-emergence of KPC despite initial containment emphasises the need for constant vigilance in the microbiology laboratory and ongoing maintenance of infection control and antimicrobial stewardship activity.

The RBMX gene as a candidate for the Shashi X-linked intellectual disability syndrome.

A novel X-linked intellectual disability (XLID) syndrome with moderate intellectual disability and distinguishing craniofacial dysmorphisms had been previously mapped to the Xq26-q27 interval. On whole exome sequencing in the large family originally reported with this disorder, we identified a 23 bp frameshift deletion in the RNA binding motif protein X-linked (RBMX) gene at Xq26 in the affected males (n = 7), one carrier female, absent in unaffected males (n = 2) and in control databases (7800 exomes). The RBMX gene has not been previously causal of human disease. We examined the genic intolerance scores for the coding regions and the non-coding regions of RBMX; the findings were indicative of RBMX being relatively intolerant to loss of function variants, a distinctive pattern seen in a subset of XLID genes. Prior expression and animal modeling studies indicate that loss of function of RBMX results in abnormal brain development. Our finding putatively adds a novel gene to the loci associated with XLID and may enable the identification of other individuals affected with this distinctive syndrome.

A rare case of nasopharyngeal carcinoma with widespread CNS metastases.

Nasopharyngeal cancer is unique among head and neck cancers. Despite definitive treatment, there is a high rate of recurrence, most commonly in the bone, lung or liver. Brain metastases and particularly, leptomeningeal carcinomatosis are extremely rare. We present a case of recurrent nasopharyngeal carcinoma with brain metastases and leptomeningeal carcinomatosis in the absence of local recurrence and systemic metastases.

Double trouble: rugby associated simultaneous rupture of flexor digitorum profundus tendon in zones I and III.

Sporting-related finger injuries are common in the setting of contact sports. Traumatic rupture of the flexor digitorum profundus tendon (FDP) from its insertion point has been described as 'jersey' or 'rugger' finger. We report a case of jersey finger associated with a zone III intra-tendinous rupture in a 13 year-old boy who presented seven weeks post injury. In the literature to date, only one previous case has described a sporting-related simultaneous 'double' FDP rupture.

Health-related quality of life, surgical and aesthetic outcomes following microvascular free flap reconstructions: an 8-year institutional review.

INTRODUCTION: Microvascular free flap reconstruction has revolutionised the reconstruction of complex defects of traumatic, oncological, congenital and infectious aetiologies. Complications of microvascular free flap procedures impact negatively on patient post-operative course and outcome. METHODS: We performed a retrospective analysis of 102 consecutive patients undergoing 108 free flap procedures at a tertiary referral centre over an 8-year period. Logistic regression analysis was used to identify factors predictive of free flap complications. Health-related quality of life (HRQoL) and aesthetic outcomes were assessed using the Short Form 36 questionnaire and a satisfaction visual analogue scale respectively. RESULTS: In total, 108 free tissue transfers were performed; 23% were fasciocutaneous free flaps, 69% musculocutaneous and 8% osteoseptocutaneous. The overall flap success rate was 92.6%. Over a third of patients (34.3%) had flap-related complications ranging from minor wound dehiscence to total flap loss. ASA (American Society of Anesthesiologists) grade ≥2 (OR: 16.9, 95% CI: 15.3-18.1, p<0.009), history of smoking (OR: 6.1, 95% CI: 5.5-7.2, p<0.049), body mass index ≥25 kg/m(2) (OR: 21.3, 95% CI: 20.8-22.1, p<0.003), low albumin (odds ratio [OR]: 2.2, 95% confidence interval [CI]: 1.2-3.9, p<0.003) and peripheral vascular disease (OR: 6.9, 95% CI: 5.9-7.5, p<0.036) were identified as factors independently predictive of free flap complications. CONCLUSIONS: Patients undergoing uncomplicated free flap surgery and those reporting superior post-operative flap aesthesis have higher HRQoL scores. Microvascular free tissue transfer has revolutionised our approach to the reconstruction of complex defects, providing a safe, reliable procedure to restore functionality and quality of life for patients.