A cost analysis of treating postoperative periprosthetic femoral fractures following hip replacement surgery in a UK tertiary referral centre.

AIM: This study aims to evaluate costs associated with periprosthetic femoral fracture (PFF) treatment at a UK tertiary referral centre. METHODS: This study included 128 consecutive PFFs admitted from 02/04/2014-19/05/2020. Financial data were provided by Patient Level Information and Costing Systems. Primary outcomes were median cost and margin. Secondary outcomes were length of stay, blood transfusion, critical care, 30-day readmission, 2-year local complication, 2-year systemic complication, 2-year reoperation and 30-day mortality rates. Statistical comparisons were made between treatment type. Statistical significance was set at p<0.05. RESULTS: Across the cohort, median cost was £15,644.00 (IQR £11,031.00-£22,255.00) and median loss was £3757.50 (£599.20-£8296.20). The highest costs were ward stay (£3994.00, IQR £1,765.00-£7,013.00), theatre utilisation (£2962.00, IQR £0.00-£4,286.00) and overheads (£1705.10, IQR £896.70-£2432.20). Cost (£17,455.00 [IQR, £13,194.00-£23,308.00] versus £7697.00 [IQR £3871.00-£10,847.00], p<0.001) and loss (£4890.00 [IQR £1308.00-£10,009.00] versus £1882.00 [IQR £313.00-£3851.00], p = 0.02) were greater in the operative versus the nonoperative group. There was no difference in cost (£17,634.00 [IQR £12,965.00-£22,958.00] versus £17,399.00 [IQR £13,394.00-£23,404.00], p = 0.98) or loss (£5374.00 [IQR £1950.00-£10,143.00] versus £3860.00 [IQR -£95.50-£7601.00], p = 0.21) between the open reduction and internal fixation (ORIF) and revision groups. More patients required blood transfusion in the operative versus the nonoperative group (17 [17.9%] versus 0 [0.0%], p = 0.009). There was no difference in any clinical outcome between the ORIF and revision groups (p>0.05). CONCLUSION: PFF treatment costs are high with inadequate reimbursement from NHS tariff. Work is needed to address this disparity and reduce hospital costs. Cost should not be used to decide between ORIF and revision surgery.

The role of cholecystectomy following endoscopic sphincterotomy and bile duct stone removal.

INTRODUCTION: Choledocholithiasis is common, with patients usually treated with endoscopic retrograde cholangiopancreatography (ERCP) and subsequent cholecystectomy to remove the presumed source of common bile duct (CBD) stones. However, previous investigations into the management of patients following ERCP have focused on recurrent CBD stones, negating the risks of cholecystectomy. This article appraises the role of cholecystectomy following successful endoscopic clearance of bile duct stones. METHODS: Patients undergoing ERCP and CBD clearance for choledocholithiasis at St James's University Hospital January 2015-December 2018 were included. Patients were divided into those who received cholecystectomy and those managed non-operatively. Readmissions, operative morbidity, mortality and treatment costs were investigated. RESULTS: Eight hundred and forty-four patients received ERCP and CBD clearance with 3.9 years follow-up. Two hundred and nine patients underwent cholecystectomy with 15% requiring complex surgery. Three hundred and seventy-three patients were non-operatively managed. Unplanned readmissions occurred in 15% following ERCP, mostly within two years. There was no difference in readmissions between the two groups. Accounting for the entire patient pathway, non-operative management was less expensive. CONCLUSIONS: The majority of patients do not require readmission following ERCP for CBD stones, and cholecystectomy did not reduce the risk of readmission. Few patients have recurrent CBD stones, but complex biliary surgery is frequently required. Routine cholecystectomy following ERCP needs to be re-evaluated and a more stratified approach to future risk developed.

A rare iatrogenic association of syndrome of inappropriate secretion of antidiuretic hormone, neuroleptic malignant syndrome and rhabdomyolysis.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is considered the prevalent cause of hyponatremia in hospitalized patients. Neuroleptic malign syndrome (NMS) is an idiosyncratic drug reaction showing fever, dysautonomia and rigidity with increased levels of Creatinine-phosphokinase (CPK) dependent on leakage of muscle contents into the circulation and defined as rhabdomyolysis. Although different diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur, particularly during treatment with atypical antipsychotics. We here present a case report of a psychiatric patient affected by a SIADH complicated with NMS/rhabdomyolysis, induced by second-generation (atypical) antipsychotic drugs in combination with carbamazepine and promazine.

Localized herpes zoster infection: a rare cause of syndrome of inappropriate secretion of antidiuretic hormone.

Hyponatremia is the most common electrolyte abnormality observed in clinical practice and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is diagnosed in nearly 40% of the hospitalized hyponatremic patients. We present a case report of herpes zoster infection causing a severe hyponatremia/hypokalemia. This rare association between SIADH and varicella-zoster virus infection is described in only few case in the literature. In our case report, the associated hypokalemia was not related to the use of diuretics but, probably, dependent on the frank serum hyposmolality able to induce an aldosterone release.

Radioguided thyroidectomy for follicular tumors: Multicentric experience.

BACKGROUND: The diagnosis of thyroid nodular diseases requires an integrated approach that has been widely established over the past years. This strategy includes: ultrasonography (US) with; implemented Color-Power-Doppler, conventional scintigraphy also with positive indicators, specific pathological studies targeted by immunohistochemically-assays, and the fine needle; aspiration biopsy (FNAB), which, usually, in case of "Follicular Lesions" (10-20%) findings is; unable to distinguish carcinoma from follicular adenoma, then indicating the necessity of surgery to; obtain a correct diagnosis. The aim of this study was to evaluate the role of the scintigraphy with; positive indicators, both preoperatively in diagnostic approach of the thyroid nodules and; intraoperatively as a guide to the extension of the surgical excision. METHODS: On 4482 Thyroidectomy performed, we selected 360 cases of follicular neoplasms (192; females and 168 males). In the preoperative phase, these patients underwent 99 m Tc-sestaMIBI; scintigraphy with both early (10 min) and late (2 h) image acquisition, which were later; compared to the ones obtained by image subtraction of means 99 m Tc-pertechnetate. Following the; sestamibi administration before intervention, we selected the most up-taking nodularity with the; assistance of a specific surgical probe (Neoprobe), quantifying uptake with relation to the surgical pathology, for an amount of 324 total thyroidectomies and 36 hemi thyroidectomies. RESULTS: In all cases of multinodular goiter the benign nodules showed an intraoperative low sestamibi uptake whereas follicular carcinomas showed both a high preoperative uptake and, as a; percentage, the highest values of intraoperative uptake; on the other hand, follicular adenomas had; both pre-and intraoperative mean values of uptake. On the contrary, papillary carcinomas only; showed a mild uptake. CONCLUSIONS: Preoperative sestamibi scintigraphy confirmed its importance in improving the information obtained through different diagnostic investigations. Also intraoperatively, it pointed; out high-risk nodules more accurately. Therefore, radio (Sestamibi) guided surgery could have an; interesting rule in the thyroid follicular lesion treatment.

Intercellular adhesion molecule-1 is upregulated via the protein kinase C pathway in human thyroid carcinoma cell lines.

Nonantigen specific adhesion systems lymphocyte function-associated antigen 1/intercellular adhesion molecule (LFA-1/ICAM-1) and cluster designation 2/lymphocyte function-associated antigen 3 (CD2/LFA-3) are considered a crucial step in immune-mediated cell-cell adhesion reactions. In particular, the LFA-1/ICAM-1 system is deeply involved in major histocompatibility system (MHC)-restricted and non-MHC-restricted cellular cytotoxicity of effector cells against cancer tissues. We have investigated in human thyroid carcinoma cell lines the role of the protein kinase C (PKC) pathway on ICAM-1 expression. Incubation with tissue plasminogen activator (TPA), an agonist of PKC, of two papillary (NPA and TPC-1) and one anaplastic (ARO) carcinoma cell lines induced an ICAM-1 upregulation of both protein and mRNA production. This phenomenon was dependent on RNA and protein synthesis and was inhibited by PKC antagonists such as staurosporine and H-7. A parallel increase in the soluble form of ICAM-1 followed the upregulation of cellular ICAM-1 levels induced by TPA. In conclusion, the PKC pathway is involved in the regulation of ICAM-1 expression in human thyroid carcinoma cell lines. Further studies are necessary to clarify the effects of the PKC pathway on the diffusion of thyroid tumors.

Cell-to-cell contact modulates the expression of the beta 1 family of integrins in primary cultures of thyroid cells.

The expression of the beta 1 family of integrins was studied in normal thyroid tissue cultures and monolayer cell cultures. The expression of the various subunits was measured by flow cytofluorometry with specific monoclonal antibodies and by Northern analysis. In monolayer cell cultures but not in tissue cultures, the expression of the alpha 3 subunit on the cell membrane progressively increased soon after plating, reaching a 30-fold higher intensity. The alpha 2 subunit, not detectable in native follicular cells, was expressed de novo and reached a remarkable high level. Up-regulation of alpha 2 and alpha 3 in monolayer cell cultures was serum-independent and preceded the expression of proliferating cell nuclear antigen, [3H]thymidine incorporation, and cell replication. Northern analysis demonstrated an increased level of beta 1 integrin mRNA. The increase of alpha 2 and alpha 3 was readily reversible since the expression of these molecules returned to a lower level when cultures reached a high cell density. Down-regulation did not occur until cell cultures were confluent. When cells from high cell density and low integrin expression were harvested and sparsely seeded in culture, up-regulation of integrins was observed again, while rapid reaggregation of isolated cells inhibited this phenomenon. Altogether these data suggest that cell-to-cell contact may regulate the expression of beta 1 integrins in thyroid primary cultures.

Retinoic acid induces intercellular adhesion molecule-1 hyperexpression in human thyroid carcinoma cell lines.

The expression of intercellular adhesion molecule-1 (ICAM-1) in tumoral tissues may promote their interaction with the immune system and cytotoxic effect on tumoral cells. This observation led to the investigation of ICAM-1 expression and modulation in different tumoral cell systems in vitro. Recently, retinoic acid-responsive elements have been found in the 5'-regulatory region of the human ICAM-1 gene. In the present study, we investigated, by flow cytometry, the effect of retinoic acid on the surface expression of ICAM-1 in human thyroid carcinoma cell lines. Two papillary (NPA and TPC-1), one follicular (WRO), one anaplastic (ARO) and one immortalized fetal (TAD-2) cell line have been studied. All of them produced constitutively ICAM-1; its surface expression and specific messenger ribonucleic acid (mRNA) levels were increased significantly by retinoic acid in all except the WRO cell line. ICAM-1 hyperexpression by retinoic acid was time dependent, reversible, and dependent on mRNA and protein synthesis. Furthermore, cytokines, such as interferon-gamma and tumor necrosis factor-alpha, both individually and, to a greater extent, in combination with retinoic acid, increased ICAM-1 surface expression and its mRNA levels. In conclusion, retinoic acid is able to induce ICAM-1 up-regulation via mRNA accumulation in human thyroid carcinoma cell lines.

Loss of polarity and de novo expression of the beta 1 family of integrins in thyroid tumors.

The expression and cell-membrane distribution of the beta 1 family of integrins (very-late-activation antigens, VLA) were investigated in benign and malignant human thyroid tumors. We compared tissue samples of normal glands, nodular goiters, adenomas and carcinomas. We also examined 3 thyroid-carcinoma cell lines cultured in vitro. The expression of subunits of the beta 1 family of integrins was assessed by flow cytometry and specific antibodies in dispersed single-cell suspensions and by immunofluorescence on frozen tissue sections. In contrast to the heterogeneity of the expression of beta 1 integrins observed in other tumors, thyroid neoplastic lesions showed a remarkably constant VLA profile. In all tumors, benign as well as malignant, and in carcinoma cell lines, all sub-units of beta 1 integrins were expressed at high levels. While sub-units alpha 1, alpha 3, alpha 5, alpha 6 and occasionally alpha 2 were also present in a cell sub-set of normal glands and nodular goiters, expression of alpha 4 was restricted to neoplastic lesions; this integrin can be therefore considered an antigen associated with thyroid tumors. It has been reported that in normal glands and in nodular goiters, the expression of beta 1 integrins is restricted to the basal-cell membrane. Immunofluorescence on tissue sections showed instead that, in adenomas and carcinomas, the polarized distribution of these integrins on the cell membrane is lost.

Integrin expression in thyroid cells from normal glands and nodular goiters.

To assess the expression of the very late antigens family of the integrin superfamily in normal and diseased thyroid glands, tissue specimens were digested to a single cell suspension and analyzed by flow cytometry with antibodies against the common beta 1 chain and the six alpha chains known to be associated to beta 1. In multinodular goiters, two cell populations were recognized. The thyroglobulin containing follicular cell population, represented the majority of cells; a minor population was composed of leukocytes. In normal glands, more than 97% of follicular cells expressed the beta 1 chain, associated with high levels of alpha 3 and very low levels of alpha 1, alpha 5, and alpha 6. The remaining cells (< 3%) expressed the beta 1 chain with a 10-fold higher intensity, associated with relatively high levels of alpha 1, alpha 5, and alpha 6, in addition to alpha 3. This small subset was much more represented in multinodular goiters, where it ranged from 10-60% of the total follicular cell population. Immunofluorescence on tissue sections showed that very late antigens were mostly located on the basal cell membrane and that in multinodular goiters cells expressing the alpha 1, alpha 5, and alpha 6 chains occurred in clusters.