Clinicopathological conference

In October 1969, professor V.G. Griffiths inaugurated monthly clinicopathological conferences at St. Luke's Hospital Malta. Two of the case studies presented at the April 1970 meeting are hereby published. A guest participant was professor Linell, of the University Institute for Pathology, associated with the Almanna Sjukhuset of Malmo, Sweden, who was then visiting the medical school. The main focus of the subject of the conference is on tumours of the kidneys and ureters, whereby an interesting discussion about the cases in question is presented, outlining the respective detailed medical examinations and evaluations processes.peer-reviewe

Pyogenic granuloma as a surrogate indicator of deep seated foreign bodies: A case report

Although pyogenic granulomas are often clinically associated with foreign bodies or recurrent traumatic injury, this association is not well documented. We report a case of a recurrent, intractable pyogenic granuloma due to a missed foreign body. An extensive search retrieved no previous literature reporting this association. This lack of evidence bases may hinder the hand surgeon from extending the wound incision and thorough exploration. Recurrent pyogenic granulomas should lead the hand surgeon to entertain the possibility of a missed foreign body

Tnehid ta’ ltim

Ġabra ta’ poeżiji u proża li tinkludi: Minn fuq il-Barrakka ta’ K. Xuereb – Triqat Mitlufa ta’ Ġorġ Pisani – Għall-mewt ta’ G. K. Chesterton ta’ Karmenu Vassallo – Imħabba u mibegħda ta’ Ġużè Chetcuti – Mill-mewt għall-ħajja! ta’ R. M. B. – Tnehid ta’ ltim ta’ Mario Agius.N/

Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge city over-75s cohort (CC75C) study.

Key neuropathological changes associated with late-onset dementia are not fully understood. Population-based longitudinal studies offer an opportunity to step back and examine which pathological indices best link to clinical state. CC75C is a longitudinal study of the population aged 75 and over at baseline in Cambridge, UK. We report on the first 213 participants coming to autopsy with sufficient information for an end of life dementia diagnosis. Clinical diagnosis was ascertained by examining retrospective informant interviews, survey responses, and death certificates according to DSM-IV criteria. The neuropathological protocol was based on the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Clinical dementia was present in 113 participants (53%): 67% with Alzheimer's disease, 4% vascular dementia, 22% mixed dementia, and 1% dementia with Lewy bodies. As Alzheimer-type pathology was common, the mutually blinded clinical and neuropathological diagnoses were not strongly related. Multivariable analysis identified associations between dementia during life and entorhinal cortex neuritic plaques, hippocampal diffuse plaques, neocortical neurofibrillary tangles, white matter pallor, Lewy bodies, and hippocampal atrophy. These results were consistent in those with clinical Alzheimer's disease. Vascular pathologies, especially microinfarcts, were more common in those with clinical diagnoses including vascular dementia. Alzheimer-type and cerebrovascular pathology are both common in the very old. A greater burden of these pathologies, Lewy bodies, and hippocampal atrophy, are associated with a higher risk of, but do not define, clinical dementia in old age

When birth is not as expected: a systematic review of the impact of a mismatch between expectations and experiences.

BACKGROUND: Pregnancy and childbirth are significant events in women's lives and most women have expectations or plans for how they hope their labour and birth will go. It is possible that strong expectations about labour and birth lead to dissatisfaction or other negative outcomes if these expectations are not met, but it is not clear if this is the case. The aim was therefore to synthesise prospective studies in order to understand whether unmet birth expectations are associated with adverse outcomes for women, their partners and their infants. METHOD: Searches were carried out in Academic Search Complete; CINAHL; Medline; PsycINFO, PsychArticles, PubMed, SCOPUS and Web of Science. Forward and backward searches were also completed. Studies were included if they reported prospective empirical research that examined the association between a mismatch in birth expectations/experience and postnatal outcomes in women, their children and/or their partners. Data were synthesised qualitatively using a narrative approach where study characteristics, context and methodological quality were extracted and summarised and then the differences and similarities among studies were used to draw conclusions. RESULTS: Eleven quantitative studies were identified for inclusion from nine countries. A mismatch between birth expectations and experiences was associated with reduced birth satisfaction. Three studies found a link between a mismatch and the development of postnatal post-traumatic stress disorder (PTSD). The evidence was inconsistent for postnatal depression, and fear of childbirth. Only one study looked at physical outcomes in the form of health-related quality of life. CONCLUSIONS: A mismatch between birth expectations and experiences is associated with birth satisfaction and it may increase the risk of developing postnatal PTSD. However, it is not clear whether a mismatch is associated with other postnatal mental health conditions. Further prospective research is needed to examine gaps in knowledge and provide standardised methods of measuring childbirth expectations-experiences mismatch. To ensure women's expectations are met, and therefore experience a satisfying birth experience, maternity providers should provide sensitive care, which acknowledges women's needs and preferences, is based on open and clear communication, is delivered as early in pregnancy as possible, and enables women to make their own decisions about care. TRIAL REGISTRATION: Protocol registration: PROSPERO CRD42020191081

Expression of the neuropathy-associated MTMR2 gene rescues MTM1-associated myopathy

Myotubularins (MTMs) are active or dead phosphoinositides phosphatases defining a large protein family conserved through evolution and implicated in different neuromuscular diseases. Loss-of-function mutations in MTM1 cause the severe congenital myopathy called myotubular myopathy (or X-linked centronuclear myopathy) while mutations in the MTM1-related protein MTMR2 cause a recessive Charcot-Marie-Tooth peripheral neuropathy. Here we aimed to determine the functional specificity and redundancy of MTM1 and MTMR2, and to assess their abilities to compensate for a potential therapeutic strategy. Using molecular investigations and heterologous expression of human MTMs in yeast cells and in Mtm1 knockout mice, we characterized several naturally occurring MTMR2 isoforms with different activities. We identified the N-terminal domain as responsible for functional differences between MTM1 and MTMR2. An N-terminal extension observed in MTMR2 is absent in MTM1, and only the short MTMR2 isoform lacking this N-terminal extension behaved similarly to MTM1 in yeast and mice. Moreover, adeno-associated virus-mediated exogenous expression of several MTMR2 isoforms ameliorates the myopathic phenotype owing to MTM1 loss, with increased muscle force, reduced myofiber atrophy, and reduction of the intracellular disorganization hallmarks associated with myotubular myopathy. Noteworthy, the short MTMR2 isoform provided a better rescue when compared with the long MTMR2 isoform. In conclusion, these results point to the molecular basis for MTMs functional specificity. They also provide the proof-of-concept that expression of the neuropathy-associated MTMR2 gene improves the MTM1-associated myopathy, thus identifying MTMR2 as a novel therapeutic target for myotubular myopathy

Diet and Physical Activity for the Prevention of Noncommunicable Diseases in Low- and Middle-Income Countries: A Systematic Policy Review

Background: Diet-related noncommunicable diseases (NCDs) are increasing rapidly in low-and middle-income countries (LMICs) and constitute a leading cause of mortality. Although a call for global action has been resonating for years, the progress in national policy development in LMICs has not been assessed. This review of strategies to prevent NCDs in LMICs provides a benchmark against which policy response can be tracked over time. Methods and Findings: We reviewed how government policies in LMICs outline actions that address salt consumption, fat consumption, fruit and vegetable intake, or physical activity. A structured content analysis of national nutrition, NCDs, and health policies published between 1 January 2004 and 1 January 2013 by 140 LMIC members of the World Health Organization (WHO) was carried out. We assessed availability of policies in 83% (116/140) of the countries. NCD strategies were found in 47% (54/116) of LMICs reviewed, but only a minority proposed actions to promote healthier diets and physical activity. The coverage of policies that specifically targeted at least one of the risk factors reviewed was lower in Africa, Europe, the Americas, and the Eastern Mediterranean compared to the other two World Health Organization regions, South-East Asia and Western Pacific. Of the countries reviewed, only 12% (14/116) proposed a policy that addressed all four risk factors, and 25% (29/116) addressed only one of the risk factors reviewed. Strategies targeting the private sector were less frequently encountered than strategies targeting the general public or policy makers. Conclusions: This review indicates the disconnection between the burden of NCDs and national policy responses in LMICs. Policy makers urgently need to develop comprehensive and multi-stakeholder policies to improve dietary quality and physical activity

Validation of the new consensus criteria for the diagnosis of corticobasal degeneration

BACKGROUND: Corticobasal degeneration (CBD) is a complex neurodegenerative disorder. Accurate diagnosis is increasingly important, with the advent of clinical trials of drugs aimed at modifying the underlying tau pathology. CBD often presents with a ‘corticobasal syndrome’ including impairments of movement and cognition. However, patients with similar corticobasal syndromes can have neurodegenerative pathologies that are not CBD. In addition, patients with CBD may present with aphasia or behavioural change. The clinical diversity of CBD and mimicry by non-CBD pathologies hinders accurate diagnosis. METHODS: We applied the new consensus criteria of Armstrong and colleagues et al 1 to a cohort of patients with detailed longitudinal clinical evaluation and neuropathology. RESULTS: In patients with pathologically confirmed CBD, accuracy of diagnosis was similar under the new and previous criteria: 9/19 (47%) met criteria for probable CBD at presentation, 13/19 (68%) at last clinical assessment. Patients with a corticobasal syndrome but without CBD pathology all (14/14) met the new diagnostic criteria of probable or possible CBD, demonstrating that the new criteria lacks the necessary specificity for an accurate ante mortem clinical diagnosis of CBD. None of the clinical features used in the new criteria were more common in the patients with CBD pathology (n=19) than without (n=14). CONCLUSIONS: The Armstrong criteria usefully broadens the recognised clinical phenotype of CBD but does not sufficiently improve the specificity of diagnosis to increase the power of clinical trials or targeted applications of tau-based disease-modifying therapies. Further work is required to show whether biomarkers could be more effective than clinical signs in the diagnosis of CBD

Exploring the evidence base for how people with dementia and their informal carers manage their medication in the community:a mixed studies review

BACKGROUND: Little is known about the general medicines management issues for people with dementia living in the community. This review has three aims: firstly to explore and evaluate the international literature on how people with dementia manage medication; assess understanding of medicines management from an informal carers perspective; and lastly to understand the role that healthcare professionals play in assisting this population with medicines management. METHODS: A mixed studies review was conducted. Web of Knowledge, PubMed and Cochrane Library were searched post-1999 for studies that explored medicines management in people with dementia dwelling in the community, and the role healthcare professionals play in supporting medicines management in people with dementia. Following screening, nine articles were included. Data from included studies were synthesised using a convergent synthesis approach and analysed thematically to combine findings from studies using a range of methods (qualitative, quantitative and mixed methods). RESULTS: Four themes were generated from the synthesis: The nature of the disease and the effects this had on medicines management; the additional responsibilities informal carers have; informal caregivers' knowledge of the importance of managing medication and healthcare professionals' understanding of medicines management in people with dementia. Consequently, these were found to affect management of medication, in particular adherence to medication. CONCLUSIONS: This review has identified that managing medication for people with dementia dwelling in the community is a complex task with a frequently associated burden on their informal caregivers. Healthcare professionals can be unaware of this burden. The findings warrant the need for healthcare professionals to undergo further training in supporting medicines management for people with dementia in their own homes

Lewy Body Variant of Alzheimer's Disease: Selective Neocortical Loss of t-SNARE Proteins and Loss of MAP2 and α-Synuclein in Medial Temporal Lobe

Lewy bodies (LBs) appear in the brains of nondemented individuals and also occur in a range of neurodegenerative disorders, such as dementia with Lewy bodies (DLB) and Parkinson's disease. A number of people with a definite diagnosis of Alzheimer's disease (AD) also exhibit these intraneuronal inclusions in allo- and/or neocortical areas. The latter, referred to as Lewy body variant of AD (LBV), bears a clinical resemblance to AD in terms of age at onset, duration of illness, cognitive impairment, and illness severity. Since the presence of LBs is accompanied by neuronal cytoskeleton changes, it is possible that the latter may influence neuronal connectivity via alterations to the synaptic network. To address this, we examined the expression of synaptic proteins (synaptophysin, syntaxin, SNAP-25, and α-synuclein) and two cytoskeletal proteins (tau and MAP2) in the brain tissue of subjects enrolled in a population-based autopsy study (n = 47). They were divided into groups with no memory problems (control group, n = 15), LBV (n = 5), AD devoid of LBs (n = 17), cerebrovascular dementia (n = 3), and mixed dementia (n = 7). The LBV and AD groups had a similar degree of cognitive impairment and neuropathological staging in terms of Braak staging and CERAD score. In comparison with the control group and the dementia groups without LBs, the LBV group had significantly lower levels of syntaxin and SNAP-25 (23%) in the neocortex, and depletion of MAP2 (64%), SNAP-25 (34%), and α-synuclein (44%) proteins in the medial temporal lobes. These findings suggest that the t-SNARE complex deficit present in LBV may be associated with the presence of LB-related pathology and may explain the more profound cholinergic loss seen in these patients