Staff Publication

Real-world Effectiveness and Safety of Pazopanib in Patients With Intermediate Prognostic Risk Advanced Renal Cell (2018)

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Type of publication:
Conference abstract

Author(s):
Procopio G.; Bamias A.; Schmidinger M.; Hawkins R.; Sanchez A.R.; Estevez S.V.; *Srihari N.; Kalofonos H.; Bono P.; Pisal C.B.; Hirschberg Y.; Dezzani L.; Ahmad Q.; Rodriguez C.S.; Jonasch E.

Citation:
Annals of Oncology (2018) 29 (suppl_8): p.313

Abstract:
Introduction: The objective of this study was to determine the effectiveness and safety of pazopanib in patients with intermediate-risk advanced/metastatic renal cell carcinoma in the PRINCIPAL study (NCT01649778). Patients and Methods: Patients had clear-cell advanced/metastatic renal cell carcinoma and met intermediaterisk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Assessments included progression-free survival, overall survival, objective response rate, and safety. We also evaluated effectiveness based on number of risk factors, age, and performance status (PS), as well as safety in older and younger patients.
Result(s): Three hundred forty-three and 363 intermediate-risk MSKCC and IMDC patients were included, respectively. The median progression-free survival was 13.8 months (95% confidence interval [CI], 10.7-18.1 months) and 7.4 months (95% CI, 6.2-10.3 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 13.1 months (95% CI, 10.7-18.1 months) and 8.1 months (95% CI, 6.4-10.7 months) for patients with 1 and 2 IMDC risk factors, respectively. The median overall survival was not reached and was 15.2 months (95% CI, 12.3-26.5 months) for patients with 1 and 2 MSKCC risk factors, respectively, and 33.9 months (95% CI, 33.9 months to not estimable) and 19.4 months (95% CI, 14.3 months to not estimable) with 1 and 2 IMDC risk factors, respectively. A lower overall response rate was observed with Eastern Cooperative Oncology Group PS >= 2 (vs. PS < 2). All-grade treatment-related adverse events occurred in approximately 63% of patients, and the safety profile among older and younger patients was similar.
Conclusion(s): Outcomes with pazopanib in intermediate-risk patients suggest that patients can be further stratified by number of risk factors (1 vs. 2) and Eastern Cooperative Oncology Group PS (< 2 vs. >= 2) to more accurately predict outcomes. Patients with intermediate-risk advanced renal cell carcinoma are a heterogeneous population, having either 1 or 2 risk factors. It is unclear whether all patients in this risk category should be treated similarly. A secondary analysis of the PRINCIPAL study of pazopanib found that patients can be stratified by number of risk factors and Eastern Cooperative Oncology Group performance status to more accurately predict outcomes.

Coeliac disease (2019)

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Type of publication:
Journal article

Author(s):
*Butterworth J.; *Los L.

Citation:
Medicine (United Kingdom); 2019; vol. 47, no. 5, p. 314-319

Abstract:
Coeliac disease (CD) is a common, chronic, immune-mediated small bowel enteropathy resulting from gluten exposure in genetically susceptible individuals. Considerable clinical and immunopathological heterogeneity is seen in newly diagnosed patients, and the diagnosis is not always straightforward even for experienced physicians. Population screening using tissue transglutaminase 2 has revealed a higher prevalence of seropositivity than previously appreciated. There is a wide differential diagnosis for mucosal villous atrophy, crypt hyperplasia and increased intraepithelial lymphocyte concentrations. Life-long adherence to a gluten-free diet is currently the only recommended treatment for CD, although many newer approaches are being explored. CD is rightly described as a multisystem disorder and is associated with other gastrointestinal and non-gastrointestinal related disorders, numerous complications and possibly reduced survival. The landscape has recently expanded with the identification that some patients with symptoms suggestive of CD but without the mucosal changes seem to respond to a gluten-free diet. This group of patients are currently labelled as having non-coeliac gluten sensitivity. Controversy exists over whether this is a separate disease entity. This review briefly discusses the important clinical, immunological and therapeutic aspects of CD.

Patulous Eustachian tube obliteration using endovascular coils: A novel technique (2018)

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Type of publication:
Journal article

Author(s):
*Jolly K.; *Darr A.; Chavda S.V.; Ahmed S.K.

Citation:
Journal of Laryngology and Otology; Jun 2018; vol. 132 (no. 6); p. 564-566

Abstract:
Background: Patulous Eustachian tube is a distressing condition characterised by chronic patency of the Eustachian tube and its failure to close. Patients typically present with symptoms of autophony and aural fullness. In patients requiring surgical intervention, a variety of different procedures have been demonstrated (both transtympanic and endonasal), with limited success. Evidence of the effectiveness of a number of surgical interventions is limited to small case series only.
Objective(s): This paper describes a novel treatment for patulous Eustachian tube using a 3 mm VortX Diamond endovascular coil. Case report: A transnasal endoscopic approach was adopted, with cannulation of the Eustachian tube orifice using a Relieva sinus guide suction tube from a balloon sinuplasty set. The coil was deployed 1.5 cm deep into the Eustachian tube. Post-operative imaging was used to confirm correct positioning. Regular follow up was arranged. The patient reported complete resolution of her symptoms.
Conclusion(s): The technique has so far proved highly effective and minimally invasive. It will be employed in more patients to fully establish its effectiveness in treating patulous Eustachian tube.

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Ketoacidosis in patients on SGLT2 inhibitor: Experience from a district general hospital (2019)

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Type of publication:
Conference abstract

Author(s):
*Kandaswamy L.; *Al-Salihi A.; *Singh P.K.; *Rangan S.; *Moulik P.K.

Citation:
Diabetic Medicine; Mar 2019; vol. 36 ; p. 174

Abstract:
Introduction: European Medicines Agency recognised diabetic ketoacidosis (DKA) as a rare and serious side effect of SGLT2 inhibitors (SGLT-2i). In six months, five cases of DKA in Type 2 diabetes on SGLT-2i were diagnosed at Royal Shrewsbury hospital. Case reports: Case 1: A 63 year old lady on metformin, dapagloflozin, gliclazide with HbA1c-102mmol/mol presented with nausea, vomiting and breathlessness was treated for DKA and pneumonia with pH 7.24, blood sugar-16mmol/l, bicarbonate-17 and ketones-3.6. Case 2: A 61 year old lady on liraglutide, gliclazide, canagliflozin with HbA1c 98mmol/mol presented with nausea, vomiting and polyuria had pH 6.9, blood sugar-16.4mmol/l, bicarbonate-<3 and ketones-5.4. Cases 3, 4 and 5: Patients established on insulin treatment with compliance issues (significantly reducing and missing insulin) had DKA. One of them had associated infection.
Discussion(s): Infection predisposed to DKA in two patients. Two patients had long duration of diabetes and poorly controlled glucose on maximum oral therapy indicating reduced beta cell reserve and three were already on insulin but reduced or missed the doses. All patients were treated according to DKA protocol and made full recovery, SGLT2i was stopped and insulin commenced in two of them and continued with others. Sick day rules emphasised.
Conclusion(s): SGLT2i lowers plasma glucose through glycosuria and promotes ketogenesis. Declining beta cell reserve with increasing duration of diabetes and relative insulin deficiency at the time of stress increases the risk of DKA. Patients on SGLT-2I should be educated of these risks particularly when they have a long duration of diabetes and are established in insulin therapy.

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Variable clinical presentations of renal cyst and diabetes (RCAD) syndrome in two patients (2019)

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Type of publication:
Conference abstract

Author(s):
*Al-Salihi A.; *Kandaswamy L.; *Qamar S.; *Rangan S.; *Moulik P.; *Singh P.K.

Citation:
Diabetic Medicine; Mar 2019; vol. 36 ; p. 86

Abstract:
Maturity onset diabetes of the young Type 5 (MODY 5), known as RCAD syndrome, results from mutations in the hepatocyte nuclear factor 1-beta (HNF1B), most commonly 17q12 deletion. We present two patients with this syndrome: Patient 1: A 31 year old male presented with symptomatic hyperglycaemia. He was diagnosed with diabetes three months previously and had been treated with a sulphonylurea. His past medical history included deranged liver function tests (LFT), azoospermia and a single functioning dysplastic kidney. He had a family history of diabetes in first-degree relatives. Genetic tests confirmed HNF1B heterozygous whole gene deletion. Patient 2: A 34 year old male with diabetes diagnosed two years previously was referred for his
complex medical background. He had a history of renal problems (renal agenesis on right and cysts on left), gout and deranged LFT. His glycaemic control was adequate on Linagliptin monotherapy. Despite the absence of relevant family history, he has been referred for genetic testing.
Discussion(s): RCAD syndrome comprises 2% of all cases of MODY and features renal cysts and diabetes alongside a spectrum of other conditions such as renal dysplasia/hypoplasia/agenesis, reproductive tract anomalies, psychiatric problems, deranged LFTs and other metabolic abnormalities in various combinations. Genetic mutations can be inherited or sporadic. Absence of family history and variability in clinical manifestations can lead to delayed recognition.
Conclusion(s): Patients with RCAD syndrome can present with a varied combination of clinical features. Clinical suspicion, irrespective of family history, is key to diagnosis and management.

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The safety and efficacy of laparoscopic ventral mesh rectopexy - Can excellent outcomes be achieved in a district general (2018)

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Type of publication:
Conference abstract

Author(s):
*Yassin N.A.; *Orfanos G.; *Farquharson A.L.; *Lacy-Colson J.C.H.

Citation:
Surgical Endoscopy; Dec 2018; vol. 32; Supplement 2, p. S553

Abstract:
Introduction: Laparoscopic ventral mesh rectopexy (VMR) is a popular treatment for symptoms of obstructive defecation in patients suffering with rectal prolapse and rectorectal intussusception. The procedure is technically challenging and may result in serious complications, such as mesh erosions. This study examines the clinical and functional outcomes of patients undergoing VMR in a district general hospital.
Method(s): A retrospective analysis was made of a prospectively maintained database of all laparoscopic VMR procedures. All cases performed by 2 surgeons between February 2012 and June 2016 were included. Length of stay, post-operative complications and functional outcomes were assessed.
Result(s): One hundred patients underwent a laparoscopic VMR procedure during the study period. The mean age was 59.7 years. Nineteen of the patients had external prolapse and 81 had functional bowel symptoms with internal prolapse (rectocele and/or intussusception) as demonstrated on proctography. Pre-operative investigations and pelvic floor multi-disciplinary team (MDT) discussions were performed in all cases. Forty percent of patients had previous pelvic surgery. In the external prolapse group there were 2/19 recurrences (10%). Functional improvement was reported in 96% of the patients. There was only 1 mesh complication (1%).
Conclusion(s): Laparoscopic VMR is an effective and safe procedure for the treatment of symptoms of obstructive defecation. This procedure can be safely performed in the district general hospital setting with excellent clinical and functional outcomes. Thorough preoperative investigations, MDT discussions and standardisation of the surgical technique lead to excellent outcomes.

A 5-year follow-up of vulval swelling due to extraskeletal myxoid chondrosarcoma: A rare case report (2019)

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Type of publication:
Journal article

Author(s):
O'Neill D.; El-Ghobashy A.; Elghobashy M.; Abdelsalam H.; *Metelko M.

Citation:
Molecular and Clinical Oncology; May 2019; vol. 10 (no. 5); p. 483-486

Abstract:
Vulval extraskeletal myxoid chondrosarcoma (EMC) is a rare cause of vulval swelling, reported <10 times in the literature to date. EMC in this location is frequently misdiagnosed due to its rarity, and patients may incur delays in diagnosis and treatment. We herein present the diagnosis and management of the case of vulval EMC in a 42-year-old Caucasian female patient who presented in 2011 with a swelling on the right labium majus. The tumour was initially misdiagnosed as a Bartholin's cyst and managed conservatively. The tumour was ultimately diagnosed as EMC and treated by radical surgical excision and adjuvant radiotherapy. The aim of the present study was to report the results after a long-terms follow-up period and review the available relevant literature.

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A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy (2019)

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Type of publication:
Randomised controlled trial

Author(s):
A. Coomarasamy, A.J. Devall, V. Cheed, H. Harb, L.J. Middleton, I.D. Gallos, H. Williams, A.K. Eapen, T. Roberts, C.C. Ogwulu, I. Goranitis, J.P. Daniels, A. Ahmed, R. Bender‑Atik, K. Bhatia, C. Bottomley, J. Brewin, M. Choudhary, F. Crosfill, S. Deb, W.C. Duncan, A. Ewer, K. Hinshaw, T. Holland, F. Izzat, J. Johns, K. Kriedt, M.-A. Lumsden, P. Manda, J.E. Norman, N. Nunes, C.E. Overton, S. Quenby, S. Rao, J. Ross, A. Shahid, *M. Underwood , N. Vaithilingam, L. Watkins, C. Wykes, A. Horne, and D. Jurkovic

Citation:
New England Journal of Medicine 2019;380:p.1815-24.

Abstract:
BACKGROUND
Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy.
METHODS
We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data.
RESULTS
A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P=0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P=0.08). The incidence of adverse events did not differ significantly between the groups.
CONCLUSIONS
Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.)

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