WUTH publication: Risk factors associated with lower extremity amputation in Sudanese individuals with diabetes: The need for improvement in primary health care system

Citation: Journal of Family Medicine and Primary Care. 2021, 10(2), 985-90
Author: Alaa Tag E Elkhider, Ahmed O Almobark, Safaa Badi, Hanan Tahir, Azza Ramadan, Abbas A Khalil, Elamin Elshaikh, Mohamed H Ahmed
Abstract: Background: Lower extremity amputation (LEA) in individuals with diabetes is a serious health issue with a considerable physical and social burden. The aim of this study was to assess the prevalence and risk factors associated with LEA in diabetic foot ulcer (DFU) patients. 

Materials and methods: This was a cross-sectional health facility-based study that recruited 315 diabetes individuals with foot ulcers from the diabetes center in Khartoum, Sudan. Direct interviewing of subjects was used to obtain data, using a standardized validated questionnaire. Chi-square and logistic regression analysis were used in data analysis. 

Results: 69.5% of the diabetic participants were aged 50 years old or more, and 71.1% were males. Most of the subjects (48.2%) were diabetics for a duration of >10 years, while more than one third (37.5%) of them were diabetic for 5-10 years. The majority (89.5%) had type 2 DM, while only 10.5% were type 1 DM. Two hundred forty-five patients had a left lower foot ulcer; 55.1% of the patients' ulcers were present in the toes, while 21.6% were in the foot sole. The overall prevalence of lower limb amputation was 17.1%. Individuals with diabetes patients with LEA had a higher incidence of hypertension (P = 0.000), retinopathy (P = 0.000), nephropathy (P = 0.002), ulcer size >2.5 cm (P = 0.000), and neuropathy (P = 0.000) through Chi-square analysis. Furthermore, logistic regression analysis showed that amputation was significantly associated with retinopathy (P = 0.000), size of ulcer (P = 0.000), and neuropathy (P = 0.016). 

Conclusion: The overall prevalence of LEA was 17.1%. The primary risks factors associated with amputation were presence of neuropathy and ulcer size >2.5 cm. Presence of retinopathy predispose diabetic individuals to amputation. Amputation is associated with disability and psychological problems; therefore, there is an urgent need for more improvement in preventative measures and primary health care system in low resource setting country like Sudan in order to decrease diabetes complications, especially patient's education about diabetes management by primary care physicians. 

Keywords: Amputation; Sudan; diabetes; foot ulcer; primary care; retinopathy. 

Link to PubMed record

CCC publication: Addition of anti-thymocyte globulin in allogeneic stem cell transplantation with peripheral stem cells from matched unrelated donors improves graft-versus-host disease and relapse free survival

Citation: Clinical Lymphoma Myeloma and Leukemia. 2021
Author: M.M. Ali, B. Grønvold, M. Remberger, I.W. Abrahamsen, A.E. Myhre, G.E. Tjønnfjord, Y. Fløisand, T. Gedde-Dahl,
Abstract: Abstract: Anti-thymocyte globulin (ATG) is commonly used to prevent Graft-versus-Host Disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To evaluate the impact of ATG as part of the GvHD prophylaxis in our institution, we report the outcome of 415 patients with matched unrelated donors (MUD) transplanted for hematological malignancies with or without ATG from 2005 to 2019 at Oslo University Hospital, Norway. The following groups were compared: 1) 154 patients transplanted with peripheral blood stem cells (PBSC) without ATG 2005-2014. 2) 137 patients transplanted with bone marrow stem cells (BMSC) 2005-2019. 3) 124 patients transplanted with PBSC and ATG (PBSC + ATG) 2014-2019. Three years survival was similar in the groups; 61% following allografting with PBSC, 54% with BMSC, and 59% with PBSC+ATG. Acute GvHD grade III-IV was 14%, 14%, and 7%, chronic GvHD was 81%, 32 and 26% and extensive cGvHD 44%, 15% and 6% in the corresponding groups. Both acute and chronic GvHD were significantly reduced in the PBSC + ATG- versus the PBSC group (p < 0.05 and p < 0.001 respectively).Transplant related mortality (TRM) was 33%, 25% and 17%, (p= 0.18). Graft versus host disease and relapse free survival (GRFS) at 3 years was 43 %, 43% and 64% in the groups. Adding ATG to the GvHD prophylaxis regimen of MUD allo-HSCT with PBSC resulted in a substantial reduction of both acute and chronic GvHD without compromising the disease control, reflected in a superior 3 years GRFS. Keywords: MUD; aGvHD; cGvHD; ATG; GvHD - prophylaxis; Allo-HSCT; PBSC; BMSC

CCC publication: The growth rate and clinical outcomes of radiation induced meningioma undergoing treatment or active monitoring

Citation: J Neurooncol. 2021 Apr 22. Online ahead of print
Author: Gillespie CS, Islim AI, Taweel BA, Millward CP, Kumar S, Rathi N, Mehta S, Haylock BJ, Thorp N, Gilkes CE, Lawson DDA, Mills SJ, Chavredakis E, Farah JO, Brodbelt AR, Jenkinson MD
Abstract: INTRODUCTION: Radiation induced meningioma (RIM) incidence is increasing in line with improved childhood cancer survival. No optimal management strategy consensus exists. This study aimed to delineate meningioma growth rates from tumor discovery and correlate with clinical outcomes. METHODS: Retrospective study of patients with a RIM, managed at a specialist tertiary neuroscience center (2007-2019). Tumor volume was measured from diagnosis and at subsequent interval scans. Meningioma growth rate was determined using a linear mixed-effects model. Clinical outcomes were correlated with growth rates accounting for imaging and clinical prognostic factors. RESULTS: Fifty-four patients (110 meningiomas) were included. Median duration of follow-up was 74 months (interquartile range [IQR], 41-102 months). Mean radiation dose was 41 Gy (standard deviation [SD] = 14.9) with a latency period of 34.4 years (SD = 13.7). Median absolute growth rate was 0.62 cm3/year and the median relative growth rate was 72%/year. Forty meningiomas (between 27 patients) underwent surgical intervention after a median follow-up duration of 4 months (IQR 2-35). Operated RIMs were clinically aggressive, likely to be WHO grade 2 at first resection (43.6%) and to progress after surgery (41%). Median time to progression was 28 months (IQR 13-60.5). A larger meningioma at discovery was associated with growth (HR 1.2 [95% CI 1.0-1.5], P = 0.039) but not progression after surgery (HR 2.2 [95% CI 0.7-6.6], P = 0.181). Twenty-seven (50%) patients had multiple meningiomas by the end of the study. CONCLUSION: RIMs exhibit high absolute and relative growth rates after discovery. Surgery is recommended for symptomatic or rapidly growing meningiomas only. Recurrence risk after surgery is high.

CCC publication: Long term outcomes of patients with poor prognostic factors following Transanal endoscopic microsurgery for early rectal cancer

Citation: Colorectal Dis. 2021 Apr 26. Online ahead of print.
Author: Javed MA, Shamim S, Slawik S, Andrews T, Montazeri A, Ahmed S
Abstract: INTRODUCTION: Management of early rectal cancer following transanal microscopic anal surgery (TEMS) poses a management dilemma when the histopathology reveals poor prognostic features, due to high risk of local recurrence (LR). The aim of this study is to evaluate the oncological outcomes of such patients who either undergo surgery with total mesorectal excision (TME), receive adjuvant chemo/radiotherapy (CRDT/RT) or close surveillance only (no further treatment). METHODS: We identified patients with poor prognostic factors; pT2 adenocarcinoma, poor differentiation, deep submucosal invasion (kikuchi - SM3), lymphovascular invasion, tumour budding or R1 resection margin between 01.09.2012 and 31.01.2020 and report their oncological outcomes. RESULTS: Of the 53 patients; 18 had TME, 14 had CRDT and 14 had RT, seven patients did not have any further treatment. Median follow-up was 48 months, 12 developed recurrence and six died. Overall, 5-year survival (OS) was 88.9% and disease-free survival (DFS) was 79.2%. Compared to the surgical group, in which there were eight recurrences and two deaths, there were zero recurrences or deaths in the CRDT group, log-rank test p = 0.206 for OS and p = 0.005 for DFS. The 5-year survival rates in RT and surveillance only groups were OS 78.6%, DFS 85.7% and OS 71.5% and 71% respectively. TME assessment in the surgical group revealed grade 3 quality in seven of the 16 available reports. CONCLUSION: These findings support the strategy of adjuvant CRDT as first line treatment for patients undergoing TEMS for ERC with poor prognostic factors on initial histological assessment.

CCC publication: Theoretical investigation of the impact of different timing schemes in hypofractionated radiotherapy

Citation: Med Phys. 2021 Apr 27. Online ahead of print.
Author: Stavrev PV, Stavreva NA, Ruggieri R, Nahum AE, Tsonev P, Penev D, Pressyanov D
Abstract: PURPOSE: This study compares the effectiveness of three fractionation schemes of equal fraction size, comprising five fractions of SBRT over five days, ten days, or fifteen days respectively. METHOD: This comparative study is based on two tumour-control-probability (TCP) models that take into account tumour cell re-sensitization and repopulation during treatment; the Zaider-Minerbo-Stavreva (ZMS) and the Ruggieri-Nahum (RN) models. The ZMS model is further modified to include also re-sensitization according to the β mechanism of the linear-quadratic (LQ) model of cell killing. The modified version of the ZMS model is verified through fitting to the experimental data set of Fisher and Moulder. The study applies an idea used in a plan ranking methodology developed for the case when the specific values of the model parameters are not known. RESULTS: The TCPs of the compared regimens are calculated for various values of the model parameters and for two different values of the dose per fraction. The TCPs are presented as 2-D functions of two of the model parameters for each model correspondingly. The differences between the TCPs of each of the prolonged regimens and the TCP of the every week day regimen are also calculated for each model. CONCLUSIONS: Both models predict that the prolonged regimens are superior in terms of TCP to the every week-day ones for most of the studied cases; however this is shown to exist to a different degree by the two models. It is shown again to a different degree that reversed situations where the every week day schedule is better than the prolonged regimens are also possible. It is concluded that a 30% TCP difference observed in a clinical study in favour of the fifteen-days regimen is theoretically possible. However, the fifteen-days regimen is outperformed in terms of TCP by the every week day regimen in more cases than the regimen lasting ten days. Therefore the choice of a prolongation in time must be made with care.

CCC publication: Carfilzomib or bortezomib in combination with cyclophosphamide and dexamethasone followed by carfilzomib maintenance for patients with multiple myeloma after one prior therapy: results from a multi-centre, phase II, randomized, controlled trial (MUKfive)

Citation: Haematologica. 2021 Apr 29. Online ahead of print.
Author: Yong KL, Hinsley S, Auner HW, Bygrave C, Kaiser MF, Ramasamy K, De Tute RM, Sherratt D, Flanagan L, Garg M, Hawkins S, Williams C, Cavenagh J, Rabin NK, Croft J, Morgan G, Davies F, Owen RG, Brown SR
Abstract: The proteasome inhibitors (PIs), carfilzomib and bortezomib, are widely used to treat myeloma but head-to-head comparisons have produced conflicting results. We compared the activity of these PIs in combination with cyclophosphamide and dexamethasone (KCd vs VCd) in second line treatment using fixed duration therapy and evaluated the efficacy of carfilzomib maintenance. MUKfive was a phase II controlled, parallel group trial that randomised patients (2:1) to KCd (201) or VCd (99); responding patients on carfilzomib were randomised to maintenance carfilzomib (69) or no further treatment (72). Primary endpoints were (i) very good partial response (VGPR, non-inferiority, OR 0.8) at 24 weeks, and (ii) progression-free survival (PFS). More participants achieved ≥VGPR with carfilzomib compared to bortezomib (40.2% vs. 31.9%, OR=1.48, 90%CI:0.95,2.31; non-inferior), with a trend for particular benefit in adverse risk disease. KCd was associated with higher overall response (≥PR, 84.0% vs. 68.1%, OR=2.72, 90%CI:1.62,4.55, p=0.001). Neuropathy (grade ≥3 or ≥2 with pain) was more common with bortezomib (19.8% vs. 1.5%, p.

CCC publication: Autologous Hematopoietic Stem Cell Transplantation for Behçet's Disease: A Retrospective Survey of Patients Treated in Europe, on Behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation

Citation: Front Immunol. 2021, 12, 638709. eCollection 
Author: Puyade M, Patel A, Lim YJ, Blank N, Badoglio M, Gualandi F, Ma DD, Maximova N, Greco R, Alexander T, Snowden JA
Abstract: BACKGROUND: Behçet's Disease (BD) is an autoimmune disease mostly presenting with recurrent oral and genital aphthosis, and uveitis. Patients are rarely refractory to immunosuppressive treatments. Autologous hematopoietic stem cell transplantation (aHSCT) is a standard of care in other autoimmune diseases. Some patients with BD have been treated with aHSCT based on compassionate use. OBJECTIVES: Evaluate the outcome of aHSCT in adult patients with BD treated in member centers of the European Society for Blood and Marrow Transplantation (EBMT). METHODS: Adults who received aHSCT primarily for BD were identified retrospectively in the EBMT registry and/or in published literature. Data were extracted from either medical records of the patient or from publications. RESULTS: Eight out of 9 cases reported to the registry and extracted data of 2 further patients from literature were analyzed. Four were female, median age at onset of BD was 24y (range 9-50). Median age at aHSCT was 32y (27-51). Patients had received median 4 (2-11) previous lines of therapy (89% corticosteroids, 50% methotrexate, anti-TNFα therapy or cyclophosphamide). All patients had active disease before mobilization. Conditioning regimen was heterogeneous. Median follow-up was 48 months (range 6-240). No treatment-related mortality was reported. This procedure induced complete remission (CR) in 80%, partial remission in 10% and lack of response in 10% of the patients. Relapse rate was 30% (2 relapses in patients in CR and 1 relapse in the patient in PR) with panuveitis (n=1), aphthosis (n=2) and arthralgia (n=1). Six patients were in CR. No late complications were reported. CONCLUSION: aHSCT has an acceptable safety profile and represents a feasible and relatively effective procedure in severe and conventional treatment-resistant cases of BD and has the potential to stabilize BD in patients with life-threatening involvements.

CCC publication: Retrospective analysis of real-world treatment patterns and clinical outcomes in patients with advanced non-small cell lung cancer starting first-line systemic therapy in the United Kingdom.

Citation: BMC Cancer. 2021, 21(1), 515
Author: Lester J, Escriu C, Khan S, Hudson E, Mansy T, Conn A, Chan S, Powell C, Brock J, Conibear J, Nelless L, Nayar V, Zhuo X, Durand A, Amin A, Martin P, Zhang X, Pawar V
Abstract: BACKGROUND: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom. METHODS: Electronic prescribing records of treatment-naive patients starting first-line (1 L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response. RESULTS: In all, 1003 patients were evaluated (median age, 68 years [range, 28-93 years]; 53.9% male). Use of 1 L IO monotherapy (0-25.9%) and targeted therapy (11.8-15.9%) increased during the study period, but chemotherapy remained the most common 1 L treatment at all time points (88.2-58.2%). Median OS was 9.5 months (95% CI, 8.8-10.7 months) for all patients, 8.1 months (95% CI, 7.4-8.9 months) with chemotherapy, 14.0 months (95% CI, 10.7-20.6 months) with IO monotherapy, and 20.2 months (95% CI, 16.0-30.5 months) with targeted therapy. In the 28.6% of patients who received second-line treatment, IO monotherapy was the most common drug class (used in 51.6%). CONCLUSIONS: Although use of 1 L IO monotherapy for aNSCLC increased in the United Kingdom during the study period, most patients received 1 L chemotherapy. An OS benefit for first-line IO monotherapy vs chemotherapy was observed but was numerically smaller than that reported in clinical trials. Targeted therapy was associated with the longest OS, highlighting the need for improved treatment options for tumors lacking targetable mutations.

CCC publication: T2*-weighted MRI produces viable fetal "Black-Bone" contrast with significant benefits when compared to current sequences

Citation: Br J Radiol. 2021, May 21, 20200940. Online ahead of print
Author: Goodall AF, Barrett A, Whitby E, Fry A

Abstract: OBJECTIVES: Fetal "black bone" MRI could be useful in the diagnosis of various skeletal conditions during pregnancy without exposure to ionizing radiation. Previously suggested susceptibility-weighted imaging (SWI) is not available in the suggested form on all scanners leading to long imaging times that are susceptible to motion artefacts. We aimed to assess if an optimized T2*-weighted GRE sequence can provide viable "black bone" contrast and compared it to other sequences in the literature. METHODS: A retrospective study was conducted on 17 patients who underwent fetal MRI. Patients were imaged with an optimized T2*-weighted GRE sequence, as well as at least one other "black-bone" sequence. Image quality was scored by four blinded observers on a five-point scale. RESULTS: The T2*-weighted GRE sequence offered adequate to excellent image quality in 63% of cases and scored consistently higher than the three other comparison sequences when comparing images from the same patient. Image quality was found to be dependent on gestational age with good image quality achieved on almost all patients after 26 weeks. CONCLUSIONS: T2*-weighted GRE imaging can provide adequate fetal "black bone" contrast and performs at least as well as other sequences in the literature due to good bone to soft tissue contrast and minimal motion artefacts. ADVANCES IN KNOWLEDGE: T2*-weighted fetal "black-bone" imaging can provide excellent bone to soft tissue contrast without using ionizing radiation. It is as good as other "black bone" sequences and may be simpler and more widely implemented, with less motion artefacts.

National Epilepsy Week

This week is National Epilepsy Week - 24th-30th May 2021

WUTH publication: How Does Hypodontia Compare in Nonsyndromic Pierre Robin Sequence Versus Isolated Cleft Palate and Isolated Cleft Lip?

Citation: The Cleft palate-craniofacial journal. 2021 May 21. Online ahead of print
Author: Maria Dillon, Madhavi Seshu, Norah Flanigan, Susana Dominguez-Gonzalez
Abstract: Objective: To assess the prevalence and patterns of hypodontia in nonsyndromic Pierre Robin sequence (PRS) and compare it with hypodontia in nonsyndromic isolated cleft palates and isolated cleft lips.
Design: Retrospective cohort study.
Setting: Alder Hey Children's Hospital, United Kingdom.
Patients: Patients with nonsyndromic PRS (group 1), isolated cleft palate (group 2), and isolated cleft lip (group 3).
Main outcome measures: Hypodontia in the permanent dentition assessed from orthopantomographs.
Results: A total of 154 patients were included. Group 1 had the highest incidence of hypodontia with 47% having at least one tooth congenitally absent. Groups 2 and 3 had reduced rates of hypodontia with 27% and 19% of the groups missing teeth, respectively; 93% of cases of hypodontia in group 1 involved the absence of at least one second premolar. Of these patients, there was found to be bilateral agenesis of second premolars in 50% of cases.
Conclusions: Patients with PRS and cleft palates are more likely to have hypodontia than those with isolated cleft palates or unilateral cleft lips. Patients with PRS have more severe hypodontia than those with isolated cleft palates or unilateral cleft lips. Bilateral agenesis of lower second premolars is a commonly seen pattern among patients with PRS. In this large UK study, a similar prevalence and pattern of hypodontia to other nonsyndromic PRS populations worldwide has been demonstrated.
Keywords: Pierre Robin sequence; cleft lip; cleft palate; hypodontia.

Link to PubMed record

International Nurses Day

To celebrate International Nurses Day we put up a collection of photographs of nurses through the years.

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International Day of the Midwife - 5th May 2021

This article produced by BBC Learning and The Conversation provides a whistle-stop tour of midwifery from the18th Century to present day.
Drunken midwives and snooty surgeons: a short history of giving birth (theconversation.com)