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Normocalcaemic primary hyperparathyroidism: what is the role of parathyroid surgery?
No full textPrimary hyperparathyroidism (PHPT) is classically associated with both an elevated or 'inappropriately normal' parathyroid hormone (PTH) level and raised serum calcium. However, in clinical practice, increasing numbers of patients present with raised PTH but normal serum calcium, renal function and vitamin D; this is known as normocalcaemic PHPT (nPHPT). Studies investigating the clinical presentation of this condition have shown that patients may present with hypertension, nephrolithiasis, impaired glucose tolerance, osteoporosis and fragility fractures. The prevalence of such complications in nPHPT is similar to that in classical hypercalcaemic PHPT (hPHPT). Although the National Institute for Health and Care Excellence (NICE) have developed guidelines for the management of PHPT generally, a consensus is yet to be reached on the optimal management of nPHPT specifically. A review of the literature on parathyroidectomy in the treatment of nPHPT revealed that nPHPT patients were more likely to present with multi-glandular disease and significantly less nPHPT patients had an intra-operative PTH fall of >50% compared with those with hPHPT. These findings demonstrate that patients with nPHPT are more likely to receive bilateral neck explorations and require remedial surgery compared with hPHPT patients. Following surgery, improvements in bone mineral density (BMD) and renal stones are generally observed in those with nPHPT. Where surgery is not possible, medical management with alendronate has been shown to be effective in nPHPT patients. Given the higher incidence of multi-gland disease and greater possibility of remedial surgery in nPHPT, careful consideration of risks and benefits should be made on an individualised basis and surgery should be performed by surgeons experienced in four gland exploration
Morbidity and Outcomes After Distal Pancreatectomy for Primary Retroperitoneal Sarcoma: An Analysis by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group.
No full textBACKGROUND
Multi-visceral resection often is used in the treatment of retroperitoneal sarcoma (RPS). The morbidity after distal pancreatectomy for primary pancreatic cancer is well-documented, but the outcomes after distal pancreatectomy for primary RPS are not. This study aimed to evaluate morbidity and oncologic outcomes after distal pancreatectomy for primary RPS.
METHODS
In this study, 26 sarcoma centers that are members of the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) retrospectively identified consecutive patients who underwent distal pancreatectomy for primary RPS from 2008 to 2017. The outcomes measured were 90-day severe complications (Clavien-Dindo ≥ 3), postoperative pancreatic fistula (POPF) rate, and oncologic outcomes.
RESULTS
Between 2008 and 2017, 280 patients underwent distal pancreatectomy for primary RPS. The median tumor size was 25 cm, and the median number of organs resected, including the pancreas, was three. In 96% of the operations, R0/R1 resection was achieved. The 90-day severe complication rate was 40 %. The grades B and C POPF complication rates were respectively 19% and 5% and not associated with worse overall survival. Administration of preoperative radiation and factors to mitigate POPF did not have an impact on the risk for the development of a POPF. The RPS invaded the pancreas in 38% of the patients, and local recurrence was doubled for the patients who had a microscopic, positive pancreas margin (hazard ratio, 2.0; p = 0.042).
CONCLUSION
Distal pancreatectomy for primary RPS has acceptable morbidity and oncologic outcomes and is a reasonable approach to facilitate complete tumor resection
Evidence-based arterial access site practice in patients with acute coronary syndromes: Has SAFARI-STEMI changed the landscape?
No full textMinimal Important Differences and self-identifying treatment response in chronic inflammatory demyelinating polyneuropathy.
No full textINTRODUCTION
The use of outcome measures is recommended for chronic inflammatory demyelinating polyneuropathy (CIDP). Implications of minimal important differences (MID) to ascertain responder status are unknown. The reliability of patient-reported treatment-response in relation to clinically-relevant change is also unknown.
METHODS
We retrospectively studied 72 subjects with "definite" or "probable" CIDP evaluated at pre-specified time-intervals pre- and post-treatment. We derived MID and the minimum detectable change with 95% confidence intervals (MDC ) for four scales. Scale sensitivities were determined with applicable MID-defined cut-offs (aMIDc), to detect subjects with self-identifying treatment response through a single question.
RESULTS
The use of MID was not valid for the Medical Research Council (MRC) Sum Score, as MDC >MID. The aMIDc for the Overall Neuropathy Limitation Score (ONLS) was 1 (sensitivity: 84.7%). The aMIDc for the centile Inflammatory Rasch-built Overall Disability Scale (cI-RODS) was 8 (sensitivity: 62.3%). The aMIDc for grip strength was 4kg (sensitivity: 79.1%). MID-defined amelioration of any one scale amongst ONLS, cI-RODS or grip strength, significantly improved sensitivity to detect treatment-responders compared with the ONLS alone (McNemar's Test: p=0.008, OR: 3.36 [95% CI: 1.44-7.86]). Patient-reported improvement was highly reliable in relation to MID-defined amelioration on any one scale.
DISCUSSION
In subjects with CIDP, MID-defined amelioration of any one of 3 commonly used outcome measures offers optimum relevance and sensitivity to detect self-identifying treatment-responders. Patient reliability to single-question ascertainment of response is high in relation to MID-defined clinical relevance. These findings support use of multiple outcome measures in CIDP monitoring and justify enhanced patient involvement in the process
Familial wild-type gastrointestinal stromal tumour in association with germline truncating variants in both SDHA and PALB2.
No full textGastrointestinal stromal tumour (GIST) is a mesenchymal neoplasm arising in the gastrointestinal tract. A rare subset of GISTs are classified as wild-type GIST (wtGIST) and these are frequently associated with germline variants that affect the function of cancer predisposition genes such as the succinate dehydrogenase subunit genes (SDHA, SDHB, SDHC, SDHD) or NF1. However, despite this high heritability, familial clustering of wtGIST is extremely rare. Here, we report a mother-son diad who developed wtGIST at age 66 and 34 years, respectively. Comprehensive genetic testing revealed germline truncating variants in both SDHA (c.1534C>T (p.Arg512*)) and PALB2 (c.3113G>A (p.Trp1038*)) in both affected individuals. The mother also developed breast ductal carcinoma in-situ at age 70 years. Immunohistochemistry and molecular analysis of the wtGISTs revealed loss of SDHB expression and loss of the wild-type SDHA allele in tumour material. No allele loss was detected at PALB2 suggesting that wtGIST tumourigenesis was principally driven by succinate dehydrogenase deficiency. However, we speculate that the presence of multilocus inherited neoplasia alleles syndrome (MINAS) in this family might have contributed to the highly unusual occurrence of familial wtGIST. Systematic reporting of tumour risks and phenotypes in individuals with MINAS will facilitate the clinical interpretation of the significance of this diagnosis, which is becoming more frequent as strategies for genetic testing for hereditary cancer becomes more comprehensive
The Impact of Adult Uveitis on Quality of Life: An Exploratory Study.
No full text: This exploratory qualitative research was conducted to understand the quality of life (QoL) impacts of adult uveitis to develop a uveitis QoL item bank, and we present here the results of qualitative analysis of uveitis patient experience.: A qualitative approach with phenomenological study design was employed to explore the common QoL domains in uveitis. Data were collected using focus groups and face-to-face interviews. The sessions were audio-recorded, transcribed verbatim, and analysed thematically. NViVo software was used to perform qualitative analysis.: Eight focus groups and 10 interviews were conducted with 41 patients with uveitis. Seven QoL domains were identified, namely symptoms, emotional, activity limitation, health concerns, convenience, social, and economic impact. Although these QoL domains have been previously identified in other eye diseases, the sub-themes within each QoL domain were unique to uveitis. Participants described a variety of symptoms including increased light sensitivity, blurred vision, pain, redness, and tearing. Participants repeatedly described feeling frustrated due to prognostic uncertainty and associated discomfort. Participants were concerned about the frequent relapses of inflammation, as well as side-effects from long-term systemic medications. Uveitis affected their ability to perform daily tasks such as using computers, driving, and reading books. Direct financial impacts included reduced work hours and the costs of treatment and specialist care.: Participants with uveitis experience many symptoms in addition to medication-related inconveniences and activity limitations. The QoL issues identified will be used to develop a uveitis-specific QoL item bank
Esophagectomy or Total Gastrectomy for Siewert 2 Gastroesophageal Junction (GEJ) Adenocarcinoma? A Registry-Based Analysis.
No full textBACKGROUNDS
Due to a lack of randomized and large studies, the optimal surgical approach for Siewert 2 gastroesophageal junctional (GEJ) adenocarcinoma remains unknown. This population-based cohort study aimed to compare survival between esophagectomy and total gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma.
METHODS
Data from the National Cancer Database (NCDB) from 2010 to 2016 was used to identify patients with non-metastatic Siewert 2 GEJ adenocarcinoma who received either esophagectomy (n = 999) or total gastrectomy (n = 8595). Propensity score-matching (PSM) and multivariable analyses were used to account for treatment selection bias.
RESULTS
Comparison of the unmatched cohort's baseline demographics showed that the patients who received esophagectomy were younger, had a lower burden of medical comorbidities, and had fewer clinical positive lymph nodes. The patients in the unmatched cohort who received gastrectomy had a significantly shorter overall survival than those who received esophagectomy (median, 47 vs. 68 months [p < 0.001]; 5-year survival, 45 % vs. 53 %). After matching, gastrectomy was associated with significantly reduced survival compared with esophagectomy (median, 51 vs. 68 months [p < 0.001]; 5-year survival, 47 % vs. 53 %), which remained in the adjusted analyses (hazard ratio [HR], 1.22; 95 % confidence interval [CI], 1.09-1.35; p < 0.001).
CONCLUSIONS
In this large-scale population study with propensity-matching to adjust for confounders, esophagectomy was prognostically superior to gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma despite comparable lymph node harvest, length of stay, and 90-day mortality. Adequately powered randomized controlled trials with robust surgical quality assurance are the next step in evaluating the prognostic outcomes of these surgical strategies for GEJ cancer
Burn injury prevention in low- and middle- income countries: scoping systematic review.
No full textBackground
Burn injuries are a leading cause of morbidity and disability, with the burden of disease being disproportionately higher in low- and middle-income countries (LMIC). Burn prevention programmes have led to significant reductions in the incidence of burns in high-income countries. However, a previous systematic review published in 2015 highlighted that implementation and evaluation of similar programmes has been limited in LMIC. The objective of this scoping review and narrative synthesis was to summarise and understand the initiatives that have been carried out to reduce burn injuries in LMIC and their effectiveness.
Methods
We aimed to identify publications that described studies of effectiveness of burn prevention interventions applied to any population within a LMIC and measured burn incidence or burns-related outcomes. Suitable publications were identified from three sources. Firstly, data was extracted from manuscripts identified in the systematic review published by Rybarczyk . We then performed a search for manuscripts on burn prevention interventions published between January 2015 and September 2020. Finally, we extracted data from two systematic reviews where burn evidence was not the primary outcome, which were identified by senior authors. A quality assessment and narrative synthesis of included manuscripts were performed.
Results
In total, 24 manuscripts were identified and categorized according to intervention type. The majority of manuscripts ( = 16) described education-based interventions. Four manuscripts focused on environmental modification interventions and four adopted a mixed-methods approach. All of the education-based initiatives demonstrated improvements in knowledge relating to burn safety or first aid, however few measured the impact of their intervention on burn incidence. Four manuscripts described population-based educational interventions and noted reductions in burn incidence. Only one of the four manuscripts describing environmental modification interventions reported burns as a primary outcome measure, noting a reduction in burn incidence. All mixed-method interventions demonstrated some positive improvements in either burn incidence or burns-related safety practices.
Conclusion
There is a lack of published literature describing large-scale burn prevention programmes in LMIC that can demonstrate sustained reductions in burn incidence. Population-level, collaborative projects are necessary to drive forward burn prevention through specific environmental or legislative changes and supplementary educational programmes
Regulatory T-Cell Therapy in Liver Transplantation and Chronic Liver Disease.
No full textThe constant exposure of the liver to gut derived foreign antigens has resulted in this organ attaining unique immunological characteristics, however it remains susceptible to immune mediated injury. Our understanding of this type of injury, in both the native and transplanted liver, has improved significantly in recent decades. This includes a greater awareness of the tolerance inducing CD4 CD25 CD127 T-cell lineage with the transcription factor FoxP3, known as regulatory T-Cells (Tregs). These cells comprise 5-10% of CD4 T cells and are known to function as an immunological "braking" mechanism, thereby preventing immune mediated tissue damage. Therapies that aim to increase Treg frequency and function have proved beneficial in the setting of both autoimmune diseases and solid organ transplantations. The safety and efficacy of Treg therapy in liver disease is an area of intense research at present and has huge potential. Due to these cells possessing significant plasticity, and the potential for conversion towards a T-helper 1 (Th1) and 17 (T17) subsets in the hepatic microenvironment, it is pre-requisite to modify the microenvironment to a Treg favourable atmosphere to maintain these cells' function. In addition, implementation of therapies that effectively increase Treg functional activity in the liver may result in the suppression of immune responses and will hinder those that destroy tumour cells. Thus, fine adjustment is crucial to achieve this immunological balance. This review will describe the hepatic microenvironment with relevance to Treg function, and the role these cells have in both native diseased and transplanted livers
Genomic investigation of a suspected outbreak in a neonatal care unit in sub-Saharan Africa.
No full textA special-care neonatal unit from a large public hospital in Malawi was noted as having more frequent, difficult-to-treat infections, and a suspected outbreak of multi-drug-resistant was investigated using genomic characterisation. All bloodstream infections (BSIs) from patients in the neonatal ward (=62), and a subset of BSI isolates (=38) from other paediatric wards in the hospital, collected over a 4 year period were studied. After whole genome sequencing, the strain sequence types (STs), plasmid types, virulence and resistance genes were identified. One ST340 clone, part of clonal complex 258 (CC258) and an ST that drives hospital outbreaks worldwide, harbouring numerous resistance genes and plasmids, was implicated as the likely cause of the outbreak. This study contributes molecular information necessary for tracking and characterizing this important hospital pathogen in sub-Saharan Africa