Impact on Quality of Life After Parathyroidectomy for Asymptomatic Primary Hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is associated with a poorer quality of life. The role of neuropsychiatric symptoms in asymptomatic patients who do not display classical features of PHPT remains undefined. It is unclear whether parathyroidectomy provides immediate benefit beyond the long-term risk reduction of adverse effects. The aim of the study is to assess the effect on quality of life in patients with asymptomatic PHPT undergoing parathyroidectomy. METHODS: Consecutive patients with PHPT undergoing parathyroidectomy by a single surgeon were recruited from a single center between 2014 and 2019. All patients prospectively completed the validated EQ-5D-3L health status questionnaire preoperatively and postoperatively, comprising two components: (i) five domains including physical and mental health and (ii) visual analog scale (VAS). Biochemical and clinical indices were recorded. RESULTS: Seventy-eight patients were included, 72% female (n = 56), median age 62 y (interquartile range (IQR): 52-70), and 28 (36%) asymptomatic. A global improvement in health-related quality of life was observed with a VAS score increase from 70 (IQR: 50-80) to 80 (IQR: 70-90); P < 0.001. VAS scores also improved significantly in asymptomatic patients increasing from 77 to 85 (P = 0.014), with an overall improvement in all five domains of quality of life. The symptomatic group showed a significant improvement in anxiety/depression levels (P < 0.01), although this was not the primary complaint in any of the cases. CONCLUSIONS: Parathyroidectomy is associated with a significant improvement in the quality of life of patients with asymptomatic PHPT. In symptomatic patients, this includes a reduction in anxiety and depression. Benefits are observed as early as 2 mo postoperatively, and results suggest a potentially important cognitive and social aspect of this disease.

Are we recording postoperative complications correctly? Comparison of NHS Hospital Episode Statistics with the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: Hospital Episode Statistics (HES) data are used to measure surgical outcomes, but its quality has been considered inferior to that of clinical databases. We compare the recording accuracy of HES, an administrative database used in the National Health Service (NHS), with that of ACS NSQIP (American College of Surgeons National Surgical Quality Improvement Program), a well-established clinical database. METHODS: 1323 patient records from our hospital, common to both databases were compared for ten surgical procedures (amputation, appendicectomy, cholecystectomy, femoral hernia repair, Hartmann's procedure, incisional hernia repair, inguinal hernia repair, long saphenous vein surgery, parathyroidectomy and umbilical hernia repair) and nine postoperative complications (acute renal failure, myocardial infarction, pneumonia, pulmonary embolism, urinary tract infection, blood transfusion, septic shock, surgical site infection and wound disruption) using text strings or ICD-10 (International Classification of Diseases) codes. κ coefficient was calculated as a measure of concordance between HES and ACS NSQIP databases. RESULTS: The databases showed perfect or very good agreement in recording a majority of surgical procedures (κ coefficient range 0.82-1.0), but there was discordance in recording postoperative complications. When HES was investigated using text string or ICD-10 code, the κ coefficient range for nine postoperative complications was 0.00-0.56, indicating poor to moderate inter-rater agreement. Concordance was even less when searched by HES coder's recommended way to record postoperative complications. CONCLUSIONS: HES poorly registers postoperative complications. Suggested improvements include addition of dates when a condition is diagnosed, agreed criteria to identify postoperative complications, specifically trained coding staff for surgery and consistent use of the coding guidance.

Unexpected changes in clinical diagnosis: early abdomino-pelvic computed tomography compared with clinical evaluation.

BACKGROUND: To evaluate the value of early computed tomography (CT) on identifying clinically "unexpected" diagnosis in patients presenting with "non specific" acute abdominal pain. MATERIALS AND METHODS: All patients presenting to on-call surgeons with acute abdominal pain were eligible study participants. Patients were randomised to CT within one hour of admission or supine abdominal and erect chest radiography. Ninety-nine patients randomized to CT arm were reviewed for the purpose of this study. The number and severity of unexpected and/or incidental diagnoses detected on the CT were assessed. RESULTS: In 20 of the 99 patients CT revealed primary or secondary diagnoses, which were unexpected following the initial clinical examination and led to completely different therapeutic options. In 15 of those 20 patients CT revealed clinically unexpected conditions, whereas in two patients severe complications of the clinically suspected diagnosis were detected on CT. Five patients had significant incidental findings in addition to their primary diagnosis on CT. In two of these patient CT also revealed clinically unexpected diagnoses. CONCLUSION: Early CT has the advantage of detecting unexpected clinically significant primary and secondary diagnoses in patients presenting with acute abdominal pain and best guides the surgeon to the appropriate patient management.

Noninvasive imaging of the transcriptional activities of human telomerase promoter fragments in mice.

We have assessed the feasibility of positron emission tomography (PET) and ex vivo gamma-counting to measure the pattern of expression of telomerase promoter fragments in vivo. Promoter fragments from either the RNA [human telomerase RNA (hTR)] or the catalytic components [human telomerase reverse transcriptase (hTERT)] of the telomerase genes were used to drive the expression of the sodium iodide symporter PET reporter gene in recombinant adenoviruses. Both promoter fragments provided cancer-selective expression that could be visualized and quantitated by PET. The transcriptional activity of the hTR promoter was found to be consistently stronger than that of the hTERT promoter. Both promoters appear therefore to be good candidates for safe use in gene therapy, and PET imaging can be used to assess the selectivity of promoters in vivo. Given that this methodology is directly scalable to humans, imaging gene expression using the sodium iodide symporter PET reporter gene could be applied to measure telomerase promoter activity in humans.

Quantitative imaging of Na/I symporter transgene expression using positron emission tomography in the living animal.

Transgene expression can be measured in living animals by positron emission tomography (PET) using reporter genes associated with radiolabeled substrates or ligands. We examined here whether PET images obtained with a new reporter gene system (sodium/iodide symporter (NIS) and [124I]iodide) could provide quantitative information on gene expression in mice. Mice received various doses of recombinant adenovirus in which the expression of the NIS cDNA was driven by the CMV promoter and subsequently [124I]iodide. Postmortem gamma counting of liver biopsies was correlated to the adenovirus dose and with NIS mRNA concentration. In addition, immunohistochemically NIS-positive cells increased with higher tissue activities. Finally, a linear relationship existed between the postmortem gamma counting in liver tissues and that calculated from images obtained through small animal PET scanning (r = 0.9581), although there was a bias at high and low specific values. This systematic study on 35 animals demonstrates that quantitative information on gene expression can be obtained from PET images using the NIS reporter system. This new methodology of quantitative imaging of gene expression presents the advantage of avoiding extensive radiochemistry, an important step for more disseminated use of this emerging technology. In addition, this work supports further development of the NIS system for noninvasive assessment of gene delivery in preclinical and clinical studies.

In Vivo Noninvasive Imaging for Gene Therapy.

Gene therapy is reaching a stage where some clinical benefits have been demonstrated on patients involved in phase I/II clinical trials. However, in many cases, the clinical benefit is hardly measurable and progress in the improvement of gene therapy formulations is hampered by the lack of objective clinical endpoints to measure transgene delivery and to quantitate transgene expression. However, these endpoints rely almost exclusively on the analysis of biopsies by molecular and histopathological methods. These methods provide only a limited picture of the situation. Therefore, there is a need for a technology that would allow precise, spacio-temporal measurement of gene expression on a whole body scale upon administration of the gene delivery vector. In the field of gene therapy, a considerable effort is being invested in the development of noninvasive imaging of gene expression and this review presents the various strategies currently being developed.

Adenovirus biodistribution and noninvasive imaging of gene expression in vivo by positron emission tomography using human sodium/iodide symporter as reporter gene.

Amongst the various methods that can be developed for noninvasive monitoring of gene expression in vivo, the use of positron emission tomography (PET) appears to be the most promising both for preclinical and clinical studies. Various genes have been described as potential PET reporters, but there is a need to develop new approaches that exploit transgenes with both therapeutic and imaging potential. The Na/I symporter (NIS) gene is expressed mainly in the thyroid and is responsible for iodide accumulation in this organ. The NIS gene has been used in gene therapy experimentation. Ectopic expression of this gene in various type of malignant cells has led to radiosensitization and in some cases tumor regression in xenograft models in nude mice, highlighting the therapeutic potential of this approach. In the present study, we demonstrate the potential of the human NIS gene (hNIS) as a reporter gene. Expression of hNIS, after plasmid transfection or adenoviral gene delivery, can be monitored in vitro on incubation with (125)I. Iodide uptake in the transduced cells can be directly correlated with the levels of gene expression in vitro. Ectopic expression of the NIS gene in vivo can be monitored in biodistribution studies on intravenous injection of (125)I. Adenovirus delivery induces gene expression essentially in the liver, adrenal glands, lungs, pancreas, and spleen. Expression of hNIS in tumor xenograft models can also be detected when the virus is injected intratumorally. Finally, hNIS expression was monitored by PET after intravenous injection of (124)I, demonstrating the potential of this approach for noninvasive imaging.