Acute abdominal pain after retrievable inferior vena cava filter insertion: case report of caval perforation by an option filter

Symptomatic caval injury is rare after inferior vena cava (IVC) filter insertion. A 39-year-old woman developed acute abdominal pain after uneventful placement of a retrievable Option IVC Filter (Angiotech Pharmaceuticals, Vancouver, British Columbia, Canada). Two days after placement, computed tomography showed a right-sided retroperitoneal hematoma, and three-dimensional C-arm rotational venography confirmed limb penetration beyond the caval wall. This is the first report of this complication despite two recent studies highlighting the safety profile of this relatively new filter.     

Analysis of inborn errors of metabolism: disease spectrum for expanded newborn screening in Hong Kong

Background  Data of classical inborn errors of metabolism (IEM) of amino acids, organic acids and fatty acid oxidation are largely lacking in Hong Kong, where mass spectrometry-based expanded newborn screening for IEM has not been initiated. The current study aimed to evaluate the approximate incidence, spectrum and other characteristics of classical IEM in Hong Kong, which would be important in developing an expanded newborn screening program for the local area.

Methods  The laboratory records of plasma amino acids, plasma acylcarnitines and urine organic acids analyses from year 2005 to 2009 inclusive in three regional chemical pathology laboratories providing biochemical and genetic diagnostic services for IEM were retrospectively reviewed.

Results  Among the cohort, 43 patients were diagnosed of IEM, including 30 cases (69%) of amino acidemias (predominantly citrin deficiency, hyperphenylalaninemia due to 6-pyruvoyl-tetrahydropterin synthase deficiency and tyrosinemia type I), 5 cases (12%) of organic acidemias (predominantly holocarboxylase synthetase deficiency) and 8 cases (19%) of fatty acid oxidation defects (predominantly carnitine-acylcarnitine translocase deficiency). The incidence of classical IEM in Hong Kong was roughly estimated to be at least 1 case per 4122 lives births, or 0.243 cases per 1000 live births. This incidence is similar to those reported worldwide, including the mainland of China. The estimated incidence of hyperphenylalaninemia was 1 in 29 542 live births.

Conclusions  Our data indicate that it is indisputable for the introduction of expanded newborn screening program in Hong Kong. Since Hong Kong is a metropolitan city, a comprehensive expanded newborn screening program and referral system should be available to serve the neonates born in the area.

     

Effects of a health-social partnership transitional program on hospital readmission: a randomized controlled trial

Hospital readmission is an indicator of care quality. Studies have been conducted to test whether post-discharge transitional care programs can reduce hospital readmission, but results are not conclusive. The contemporary development of post-discharge support advocates a health and social partnership approach. There is a paucity of experimental studies examining the effects of such efforts. This study designed a health-social transitional care management program (HSTCMP) and subjected it to empirical testing using a randomized controlled trial in the medical units of an acute general hospital with 1700 beds in Hong Kong during the period of February 2009 to July 2010. Results using per-protocol analysis revealed that the HSTCMP significantly reduced readmission at 4-weeks (study 4.0%, control 10.2%, χ(2) = 7.98, p = 0.005). The intention-to-treat result also showed a lower readmission rate with the study group but the result was not significant (study 11.5%, control 14.7%, χ(2) = 1.53, p = 0.258). There was however significant improvement in quality of life, self-efficacy and satisfaction in the study group in both per-protocol and intention-to-treat analyses. The study suggests that a health-social partnership, using volunteers as substitutes for some of the professional care, may be effective for general medical patients.     

Disclosure of HIV serostatus among pregnant and postpartum women in sub-Saharan Africa: a systematic review

Disclosure of one's HIV status can help to improve uptake and retention in prevention of mother-to-child transmission of HIV services; yet, it remains a challenge for many women. This systematic review evaluates disclosure rates among pregnant and postpartum women in sub-Saharan Africa, timing of disclosure, and factors affecting decisions to disclose. PubMed and EMBASE databases were searched to identify relevant studies published between January 2000 and April 2014. Rates of HIV serostatus disclosure to any person ranged from 5.0% to 96.7% (pooled estimate: 67.0%, 95% CI: 55.7%–78.3%). Women who chose to disclose their status did so more often to their partners (pooled estimate: 63.9%; 95% CI: 56.7%–71.1%) than to family members (pooled estimate: 40.1; 95% CI: 26.2%–54.0%), friends (pooled estimate: 6.4%; 95% CI: 3.0%–9.8%), or religious leaders (pooled estimate: 7.1%; 95% CI: 4.3%–9.8%). Most women disclosed prior to delivery. Decisions to disclose were associated with factors related to the woman herself (younger age, first pregnancies, knowing someone with HIV, lower levels of internalized stigma, and lower levels of avoidant coping), the partner (prior history of HIV testing and higher levels of educational attainment), their partnership (no history of domestic violence and financial independence), and the household (higher quality of housing and residing without co-spouses or extended family members). Interventions to encourage and support women in safely disclosing their status are needed.     

A phase 2, randomized,double‐blind,placebo‐controlled study of siltuximab (anti‐IL‐6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma

We compared the safety and efficacy of siltuximab (S), an anti‐interleukin‐6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) + B in patients with relapsed/refractory multiple myeloma in a randomized phase 2 study. Siltuximab was given by 6 mg/kg IV every 2 weeks. On progression, B was discontinued and high‐dose dexamethasone could be added to S/plc. Response and progression‐free survival (PFS) were analyzed pre‐dexamethasone by European Group for Blood and Marrow Transplantation (EBMT) criteria. For the 281 randomized patients, median PFS for S + B and plc + B was 8.0 and 7.6 months (HR 0.869, P = 0.345), overall response rate was 55 versus 47% (P = 0.213), complete response rate was 11 versus 7%, and median overall survival (OS) was 30.8 versus 36.8 months (HR 1.353, P = 0.103). Sustained suppression of C‐reactive protein, a marker reflective of inhibition of interleukin‐6 activity, was seen with S + B. Siltuximab did not affect B pharmacokinetics. Siltuximab/placebo discontinuation (75 versus 66%), grade ≥3 neutropenia (49 versus 29%), thrombocytopenia (48 versus 34%), and all‐grade infections (62 versus 49%) occurred more frequently with S + B. The addition of siltuximab to bortezomib did not appear to improve PFS or OS despite a numerical increase in response rate in patients with relapsed or refractory multiple myeloma. © 2014 Wiley Periodicals, Inc. Am. J. Hematol. 90:42–49, 2015. © 2014 Wiley Periodicals, Inc.     

Practical management of myelofibrosis with ruxolitinib

Treatment for the majority of patients with myelofibrosis is primarily based on symptom control as curative allogeneic stem cell transplantation is typically offered only to younger patients, especially those with poor prognosis disease. Around 50% of patients with myelofibrosis have the JAK2^V617F mutation, but almost all patients have aberrant activation of the JAK‐STAT signalling pathway. Recent efforts have focussed on the clinical use of JAK2 inhibitors to treat myelofibrosis. In this article, we present our recommendations for the practical management of myelofibrosis with ruxolitinib, a selective inhibitor of both JAK1 and JAK2. Ruxolitinib can significantly improve the quality of life of patients with myelofibrosis. There is also increasing evidence of a positive impact on survival. Consistent with the physiological role of JAK signalling the major toxicity of ruxolitinib is cytopenia. Managing cytopenia is key to maximising the therapeutic benefit of ruxolitinib. Further research into the safety of ruxolitinib in patients with thrombocytopenia is warranted, as is its role in special subgroups of patients, such as those undergoing stem cell transplantation and those experiencing thrombosis as a major manifestation of myelofibrosis.     

Retinal Nerve Fiber Layer Thickness in Myopic,Emmetropic, and Hyperopic Children

The purpose of this study was to investigate the peripapillary retinal nerve fiber layer (RNFL) thickness in myopic, emmetropic, and hyperopic children using optical coherence tomography.Two-hundred one right eyes of subjects aged 4 to 18 years were divided into 3 groups based on their postcycloplegic spherical equivalent: myopes (<−1.0 D), emmetropes (≥−1.0 to ≤+1.0 D), and hyperopes (>+1.0 D). The RNFL was correlated with age, spherical equivalent, and axial length. The RNFL was compared between the 3 groups before and after age adjustment.The RNFL was thickest in the hyperopic group (107.2 ± 10.13 μm, n = 73), followed by the emmetropic group (102.5 ± 9.2 μm, n = 61), and then the myopic group (95.7 ± 10.3, n = 67) (all P < 0.0001). The myopic group (9.6 ± 3.9 years) was significantly older than the emmetropic (6.9 ± 2.7 years) and hyperopic (6.5 ± 1.9 years) groups (both P < 0.0001). When adjusted for age, myopes had a thinner RNFL than the other 2 groups (all P < 0.0001), but there was no RNFL thickness difference between the emmetropic and hyperopic groups (P > 0.05). A thinner RNFL was associated with an older age (r = −0.4, P < 0.0001), a more myopic spherical equivalent (r = 0.5, P < 0.0001), and a longer axial length (r = −0.4, P < 0.0001) on Pearson correlation analysis.The apparently thicker RNFL in hyperopic and emmetropic children was attributed to their younger age as compared with their myopic counterparts. When adjusted for age, only myopia was associated with a thinner RNFL, with emmetropic and hyperopic children having equal RNFL thicknesses. Advancing age, a more myopic spherical equivalent, and a longer axial length were associated with a thinner RNFL in children.     

A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)

Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gaucher’s disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is an example of an iminosugar with activity against multiple virus families that should be investigated in further safety and efficacy studies and demonstrates potential value of this drug class as antiviral therapeutics.     

Systematic mechanism-orientated approach to chronic pancreatitis pain

Pain in chronic pancreatitis(CP) shows similarities with other visceral pain syndromes(i.e.,inflammatory bowel disease and esophagitis),which should thus be managed in a similar fashion.Typical causes of CP pain include increased intrapancreatic pressure,pancreatic inflammation and pancreatic/extrapancreatic complications.Unfortunately,CP pain continues to be a major clinical challenge.It is recognized that ongoing pain may induce altered central pain processing,e.g.,central sensitization or pro-nociceptive pain modulation.When this is present conventional pain treatment targeting the nociceptive focus,e.g.,opioid analgesia or surgical/endoscopic intervention,often fails even if technically successful.If central nervous system pain processing is altered,specific treatment targeting these changes should be instituted(e.g.,gabapentinoids,ketamine or tricyclic antidepressants).Suitable tools are now available to make altered central processing visible,including quantitative sensory testing,electroencephalograpy and(functional) magnetic resonance imaging.These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes.The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved.Future research should address the circumstances under which central nervous system pain processing changes in CP,and how this is influenced by ongoing nociceptive input and therapies.Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy,leading to improved treatment of chronic pain in CP and other visceral pain disorders.     

Restoring allosterism with compensatory mutations in hemoglobin.

Abnormal human hemoglobins (HBs) with amino acid substitutions in the alpha 1 beta 2 interface have very high oxygen affinity and greatly reduced cooperativity in O2 binding compared to normal human Hb. In such abnormal Hbs with mutations at position beta 99, the intersubunit hydrogen bonds between Asp-beta 99 and Tyr-alpha 42 and between Asp-beta 99 and Asn-alpha 97 are broken, thus destabilizing the deoxyquaternary structure of these Hbs. A molecular dynamics method has been used to design compensatory amino acid substitutions in these Hbs that can restore their allosteric properties. We have designed a compensatory mutation in a naturally occurring mutant Hb, Hb Kempsey (Asp-beta 99-->Asn), and have produced it using our Escherichia coli expression plasmid pHE2. We have determined the O2 binding properties of this recombinant double mutant Hb, Hb(Asp-beta 99-->Asn and Tyr-alpha 42-->Asp) and have used 1H NMR spectroscopy to investigate the tertiary structures around the heme groups and the quaternary structure in the alpha 1 beta 2 subunit interface. Our results clearly show that the Tyr-alpha 42-->Asp replacement can substantially compensate for the functional defect of Hb Kempsey caused by the Asp-beta 99-->Asn substitution. The structural and functional information derived from this recombinant Hb provides insights into the structural basis of allosterism and the design of compensatory amino acid substitutions to restore the functional properties of other abnormal HBs associated with hemoglobinopathies.