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Background Dialysis patients and immunosuppressed renal patients are at increased risk of COVID-19 and were excluded from vaccine trials. We conducted a prospective multicentre study to assess SARS-CoV-2 vaccine antibody responses in dialysis patients and renal transplant recipients, and patients receiving immunosuppression for autoimmune disease. Methods Patients were recruited from three UK centres (ethics:20/EM/0180) and compared to healthy controls (ethics:17/EE/0025). SARS-CoV-2 IgG antibodies to spike protein were measured using a multiplex Luminex assay, after first and second doses of Pfizer BioNTech BNT162b2(Pfizer) or Oxford-AstraZeneca ChAdOx1nCoV-19(AZ) vaccine. Results Six hundred ninety-two patients were included (260 dialysis, 209 transplant, 223 autoimmune disease (prior rituximab 128(57%)) and 144 healthy controls. 299(43%) patients received Pfizer vaccine and 379(55%) received AZ. Following two vaccine doses, positive responses occurred in 96% dialysis, 52% transplant, 70% autoimmune patients and 100% of healthy controls. In dialysis patients, higher antibody responses were observed with the Pfizer vaccination. Predictors of poor antibody response were triple immunosuppression (adjusted odds ratio [aOR]0.016;95%CI0.002–0.13; p  < 0.001) and mycophenolate mofetil (MMF) (aOR0.2;95%CI 0.1–0.42; p  < 0.001) in transplant patients; rituximab within 12 months in autoimmune patients (aOR0.29;95%CI 0.008–0.096; p  < 0.001) and patients receiving immunosuppression with eGFR 15-29 ml/min (aOR0.031;95%CI 0.11–0.84; p  = 0.021). Lower antibody responses were associated with a higher chance of a breakthrough infection. Conclusions Amongst dialysis, kidney transplant and autoimmune populations SARS-CoV-2 vaccine antibody responses are reduced compared to healthy controls. A reduced response to vaccination was associated with rituximab, MMF, triple immunosuppression CKD stage 4. Vaccine responses increased after the second dose, suggesting low-responder groups should be prioritised for repeated vaccination. Greater antibody responses were observed with the mRNA Pfizer vaccine compared to adenovirus AZ vaccine in dialysis patients suggesting that Pfizer SARS-CoV-2 vaccine should be the preferred vaccine choice in this sub-group.

B cells produce alloantibodies and activate alloreactive T cells, negatively affecting kidney transplant survival. By contrast, regulatory B cells are associated with transplant tolerance. Immunotherapies are needed that inhibit B-cell effector function, including antibody secretion, while sparing regulators and minimising infection risk. B lymphocyte stimulator (BLyS) is a cytokine that promotes B-cell activation and has not previously been targeted in kidney transplant recipients. We aimed to determine the safety and activity of an anti-BLyS antibody, belimumab, in addition to standard-of-care immunosuppression in adult kidney transplant recipients. We used an experimental medicine study design with multiple secondary and exploratory endpoints to gain further insight into the effect of belimumab on the generation of de-novo IgG and on the regulatory B-cell compartment. We undertook a double-blind, randomised, placebo-controlled phase 2 trial of belimumab, in addition to standard-of-care immunosuppression (basiliximab, mycophenolate mofetil, tacrolimus, and prednisolone) at two centres, Addenbrooke's Hospital, Cambridge, UK, and Guy's and St Thomas' Hospital, London, UK. Participants were eligible if they were aged 18–75 years and receiving a kidney transplant and were planned to receive standard-of-care immunosuppression. Participants were randomly assigned (1:1) to receive either intravenous belimumab 10 mg per kg bodyweight or placebo, given at day 0, 14, and 28, and then every 4 weeks for a total of seven infusions. The co-primary endpoints were safety and change in the concentration of naive B cells from baseline to week 24, both of which were analysed in all patients who received a transplant and at least one dose of drug or placebo (the modified intention-to-treat [mITT] population). This trial has been completed and is registered with ClinicalTrials.gov, NCT01536379, and EudraCT, 2011–006215–56. Between Sept 13, 2013, and Feb 8, 2015, of 303 patients assessed for eligibility, 28 kidney transplant recipients were randomly assigned to receive belimumab (n=14) or placebo (n=14). 25 patients (12 [86%] patients assigned to the belimumab group and 13 [93%] patients assigned to the placebo group) received a transplant and were included in the mITT population. We observed similar proportions of adverse events in the belimumab and placebo groups, including serious infections (one [8%] of 12 in the belimumab group and five [38%] of 13 in the placebo group during the 6-month on-treatment phase; and none in the belimumab group and two [15%] in the placebo group during the 6-month follow-up). In the on-treatment phase, one patient in the placebo group died because of fatal myocardial infarction and acute cardiac failure. The co-primary endpoint of a reduction in naive B cells from baseline to week 24 was not met. Treatment with belimumab did not significantly reduce the number of naive B cells from baseline to week 24 (adjusted mean difference between the belimumab and placebo treatment groups −34·4 cells per μL, 95% CI −109·5 to 40·7). Belimumab might be a useful adjunct to standard-of-care immunosuppression in renal transplantation, with no major increased risk of infection and potential beneficial effects on humoral alloimmunity. GlaxoSmithKline.

We have analyzed the relationship between donor mismatches at each HLA locus and development of HLA locus–specific antibodies in patients listed for repeat transplantation. HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The number of HLA mismatches and the calculated reaction frequency of antibody reactivity against 10,000 consecutive deceased organ donors were determined for each HLA locus. Two-thirds of patients awaiting repeat transplantation were sensitized (calculated reaction frequency over 15%) and half were highly sensitized (calculated reaction frequency of 85% and greater). Antibody levels peaked after re-listing for repeat transplantation, were independent of graft nephrectomy and were associated with length of time on the waiting list (odds ratio 8.4) and with maintenance on dual immunosuppression (odds ratio 0.2). Sensitization was independently associated with increasing number of donor HLA mismatches (odds ratio 1.4). All mismatched HLA loci contributed to the development of HLA locus–specific antibodies (HLA-A: odds ratio 3.2, HLA-B: odds ratio 3.4, HLA-C: odds ratio 2.5, HLA-DRB1: odds ratio 3.5, HLA-DRB3/4/5: odds ratio 3.9, and HLA-DQ: odds ratio 3.0 (all significant)). Thus, the risk of allosensitization following failure of a first renal transplant increases incrementally with the number of mismatches at all HLA loci assessed. Maintenance of re-listed patients on dual immunosuppression was associated with a reduced risk of sensitization.

Background: Chronic pain remains a major clinical challenge, which is often resistant to conventional treatments. Spinal cord stimulation has been used for decades to manage refractory pain, traditionally relying on open-loop systems with fixed-output stimulation. However, these systems fail to account for physiological variability, leading to inconsistent pain relief. Closed-loop spinal cord stimulation represents a significant advancement by utilizing evoked compound action potentials to continuously modulate stimulation intensity in real-time, ensuring more stable and effective pain management. Methods: A comprehensive literature review was conducted using PubMed and ClinicalTrials.gov to identify and synthesize relevant published and ongoing studies with a focus on open-loop spinal cord stimulation for managing lower back pain. Results: Clinical trials, including the Avalon and Evoke studies, have demonstrated that closed-loop spinal cord stimulation provides superior pain relief, functional improvement, and reduced opioid dependence compared to traditional open-loop systems. Patients receiving closed-loop stimulation reported significantly higher rates of sustained pain reduction, improved quality of life, and fewer complications related to overstimulation. Emerging studies suggest its potential for conditions beyond back pain, such as neuropathic pain, cancer-related pain, and Raynaud’s phenomenon. Furthermore, cost-effectiveness analyses indicate that closed-loop spinal cord stimulation is a more economically viable treatment option compared to conventional medical management and open-loop systems. Conclusions: Closed-loop spinal cord stimulation represents a transformative development in neuromodulation, offering personalized and adaptive pain management that is distinct from open-loop spinal cord stimulation. Further research is warranted to explore its long-term durability, broader applications, and integration with emerging technologies in pain management.

G. E. R. LLOYD. The Ambitions of Curiosity: Understanding the World in Ancient Greece and China. New York: Cambridge University Press, 2002. Pp. xvi, 175. $22.00 (US), paper; GEOFFREY LLOYD and NATHAN SIVIN. The Way and the Word: Science and Medicine in Early China and Greece. New Haven and London: Yale University Press, 2002. Pp. xvii, 348. $35.00 (US); $22.00 (US), paper. Reviewed by Paul S. Cartledge FRANÇOIS CHAMOUX. Hellenistic Civilization, trans. Michel Roussel (in cooperation with Margaret Roussel). Oxford and Maiden: Blackwell, 2003. Pp. xii, 452. $67.95 (US). Reviewed by Daniel Ogden RAYMOND VAN DAM. Kingdom of Snow: Roman Rule and Greek Culture in Cappadocia. Philadelphia: University of Pennsylvania Press, 2002; dist. Toronto: Scholarly Book Services. Pp. viii, 290. $82.50 (CDN). Reviewed by Arthur M. Eckstein CYRIL MANGO, ed. The Oxford History of Byzantium. New York: Oxford University Press, 2002. Pp. xviii, 334. $45.00 (US). Reviewed by Sebastian Brock ROBERT MORRISSEY. Charlemagne and France: A Thousand Years of Mythology, trans. Catherine Tihanyi. Notre Dame, IN: University of Notre Dame Press, 2003. Pp. xii, 391. $40.00 (US). Reviewed by H. E. J. Cowdrey MALCOLM BARBER and KEITH BATE, eds. The Templars: Selected Sources Translated and Edited. Manchester: Manchester University Press, 2002; dist. Vancouver: University of British Columbia Press. Pp. xiv, 350. $29.95 (US), paper. Reviewed by John France IAN ROBERTSON. Tyranny under the Mande of St Peter: Pope Paul II and Bologna. Turnhout, Belgium: Brepols, 2002. Pp. x. 245. €55.00. Reviewed by David Nicholas GÁBOR KLANICZAY. Holy Rulers and Blessed Princesses: Dynastic Cults in Medieval Central Europe, trans. Éva Pálmai. New York: Cambridge University Press, 2002. Pp. xviii, 490. $95.00 (US). Reviewed by Diana Webb FlNN-ElNAR ELIASSEN, JØRGEN MlKKELSEN, and BJØRN POULSEN, eds. Regional Integration in Early Modern Scandinavia. Odense: Odense University Press, 2001; dist. Portland: ISBS. Pp. 287. $37.50 (US), paper. Reviewed by Paul Douglas Lockhart THOMAS JAMES DANDELET. Spanish Rome, 1500-1700. New Haven and London: Yale University Press, 2001. Pp. 278. $35.00 (US). Reviewed by Maria Antonietta Visceglia ANTHONY LEVI. Renaissance and Reformation: The Intellectual Genesis. New Haven and London: Yale University Press, 2002. Pp. xi, 483. $39.95 (US). Reviewed by Paul W. Knoll THOMAS B. F. CUMMINS. Toasts with the Inca: Andean Abstraction and Colonial Images on Quero Vessels. Ann Arbor: University of Michigan Press, 2002. Pp. xii, 377. $69.50 (US). Reviewed by Rebecca Stone-Miller JANET M. HARTLEY. Charles Whitworth: Diplomat in the Age of Peter the Great. Aldershot and Burlington: Ashgate, 2002. Pp. xvi, 242. $79.95 (US). Reviewed by John T. Alexander OWEN CONNELLY. On War and Leadership: The Words of Combat Commanders from Frederick the Great to Norman Schwarzkopf. Princeton and Oxford: Princeton University Press, 2002. Pp. viii, 347. $29.95 (US). Reviewed by Dennis E. Showalter EDMUND S. MORGAN. Benjamin Franklin. New Haven and London: Yale University Press, 2002. Pp. xi, 339. $24.95 (US). Reviewed by Lawrence S. Kaplan ANDREAS FAHRMEIR, OLIVIER FARON, and PATRICK WEIL, eds. Migration Control in the North Atlantic World: The Evolution of State Practices in Europe and the United States from the French Revolution to the Inter-War Period. New York: Berghahn, 2003. Pp. xiii, 322. $75.00 (US). Reviewed by Donald Harman Akenson PAUL ROBERT MAGOCSI. The Roots of Ukrainian Nationalism: Galicia as Ukraine's Piedmont. Toronto: University of Toronto Press, 2002. Pp. xi, 214. $50.00 (CDN). Reviewed by George O. Liber JEREMY KING. Budweisers into Czechs and Germans: A Local History of Bohemian Politics, 1848-1948. Princeton and Oxford: Princeton University Press, 2002. Pp. xv, 284. $39.50 (US). Reviewed by Gary B. Cohen SUSAN J. FERNANDEZ. Encumbered Cuba: Capital Markets and Revolt, 1878-1895. Gainesville: University Press of Florida, 2002; dist. Toronto: Scholarly Book Services. Pp. xii, 203. $92.50 (CDN). Reviewed by Franklin W. Knight SHIRLEY ARDENER, ed. with commentaries. Swedish Ventures in Cameroon, 1883-1923: Trade and Travel, People and Politics: The Memoir of Knut Knutson, with Supporting Material. New York: Berghahn, 2002. Pp. xv, 288. $79.95 (US), cloth; $29.00 (US), paper. Reviewed by John Flint J. L. GRANATSTEIN. Canada's Army: Waging War and Keeping the Peace. Toronto: University of Toronto Press, 2002. Pp. xv, 519. $50.00 (CDN). Reviewed by Ken Reynolds PETER MANGOLD. Success and Failure in British Foreign Policy: Evaluating the Record, 1900-2000. Basingstoke and New York: Palgrave Macmillan, 2001. Pp. viii, 243. $65.00 (US). Reviewed by John Charmley CLEMENT M. HENRY and ROBERT SPRTNGBORG. Globalization and the Politics of Development in the Middle East. New York: Cambridge University Press, 2001. Pp. xxi, 258. $55.00 (US). Reviewed by Roger Owen PETER HOLQUIST. Making War, Forging Revolution: Russia's Continuum of Crisis, 1914-1921. Cambridge, MA and London: Harvard University Press, 2002. Pp. ix, 359. $45.00 (US). Reviewed by Terence Emmons NORMAN RICH. Great Power Diplomacy: Since 1914. New York: McGraw-Hill, 2003. Pp. xxiii, 565. $42.50 (US), paper. Reviewed by Margaret Lamb AVIEL ROSHWALD. Ethnic Nationalism and the Fall of Empires: Central Europe, Russia, and the Middle East, 1914-1923. London and New York: Routledge, 2001. Pp. x. 273. $27.95 (US), paper; ACHIM MÜLLER. Zwischen Annäherung und Abgrenzung. Österreich-Ungarn und die Diskussion urn Mitteleuropa im Ersten Weltkrieg. Marburg: Tectum Verlag, 2001. Pp. 412. €25.90. Reviewed by Lothar Höbelt JOHN GRIGG. Lloyd George: War Leader, 1916-1918. London: Allen Lane, The Penguin Press, 2002. Pp. xv, 669. $55.00 (CDN). Reviewed by Sidney Aster MICHAEL HOPKINSON. The Irish War of Independence. Montreal and Kingston: McGill-Queen's University Press, 2002. Pp. xxi, 274. $60.00 (CDN). Reviewed by David Harkness BERTRAND M. PATENAUDE. The Big Show in Bololand: The American Relief Expedition to Soviet Russia in the Famine of 1921. Stanford: Stanford University Press, 2002. Pp. viii, 817. $29.95 (US), paper. Reviewed by Betty Miller Unterberger STEPHANIE BURROWS. Tucholsky and France. Leeds: Maney Publishing, 2001; dist. Portland: ISBS. Pp. x, 269. $78.00 (US), paper. Reviewed by Talbot Imlay ELEANOR M. HADLEY with PATRICIA HAGAN KUWAYAMA. Memoir of a Trustbuster: A Lifelong Adventure with Japan. Honolulu: University of Hawaii Press, 2003. Pp. viii, 175. $22.00 (US). Reviewed by Laura Hein DARLENE RIVAS. Missionary Capitalist: Nelson Rockefeller in Venezuela. Chapel Hill and London: University of North Carolina Press, 2002; dist. Toronto: Scholarly Book Services. Pp. xiv, 290. $32.95 (CDN), paper. Reviewed by William O. Walker III GERD R. UEBERSCHÄR, ed. Der deutsche Widerstand gegen Hitler: Wahmehmung und Wertung in Europa und den USA. Darmstadt: Wissenschaftliche Buchgesellschaft, 2002. Pp. 300. €49.90. Reviewed by Andreas Fahrmeir RONALD W. ZWEIG. The Gold Train: The Destruction of the Jews and the Second World War's Most Terrible Robbery. London: Allen Lane, The Penguin Press, 2002. Pp. xxiii, 311. £20.00. Reviewed by Norman J. W. Goda DAVID M. GLANTZ. The Battle for Leningrad, 1941-1944. Lawrence: University Press of Kansas, 2002. Pp. xxiii, 660. $39.95 (US). Reviewed by Catherine Andreyev ANTONIO VARSORI and ELENA CALANDRI, eds. The Failure of Peace in Europe, 1943-48. Basingstoke and New York: Palgrave Macmillan, 2002. Pp. xii, 342. $72.00 (US). Reviewed by Leopoldo Nuti EMIKO OHNUKI-TIERNEY. Kamikaze, Cherry Blossoms, and Nationalisms: The Militarization of Aesthetics in Japanese History. Chicago and London: University of Chicago Press, 2002. Pp. xvii, 411. $20.00 (US), paper. Reviewed by Karl F. Friday WILLIAM HENRY POPE, MC. Leading from the Front: The War Memoirs of Harry Pope. Waterloo: The Laurier Centre for Military Strategic and Disarmament Studies, Wilfrid Laurier University, 2002. Pp. xxiv, 248. $24.00 (CDN), paper. Reviewed by Desmond Morton T. FUJITANI, GEOFFREY M. WHITE, and LISA YONEYAMA, eds. Perilous Memories: The Asia-Pacific War(s). Durham, NC and London: Duke University Press, 2001. Pp. vi, 462. $19.95 (US), paper. Reviewed by Jeffrey G. Barlow ROGER BUCKLEY. The United States in the Asia-Pacific since 1945. New York: Cambridge University Press, 2002. Pp. x, 258. $65.00 (US), cloth; $23.00 (US), paper. Reviewed by Akira Iriye J. N. DIXIT. India-Pakistan in War and Peace. London and New York: Routledge, 2002. Pp. 501. $27.50 (US). Reviewed by Sumit Ganguly JON V. KOFAS. The Sword of Damocles: US Financial Hegemony in Colombia and Chile, 1950-1970. Westport: Praeger, 2002. Pp. xix, 238. $64.95 (US). Reviewed by Paul W. Drake WILLIAM STUECK. Rethinking the Korean War: A New Diplomatic and Strategic History. Princeton and Oxford: Princeton University Press, 2002. Pp. xiv, 285. $29.95 (US). Reviewed by James I. Matray BRENT BYRON WATSON. Far Eastern Tour: The Canadian Infantry in Korea, 1950-1953. Montreal and Kingston: McGill-Queen's University Press, 2002. Pp. xiii, 238. $34.95 (CDN). Reviewed by Steven Hugh Lee JOHN A. NAGL. Counterinsurgency Lessons from Malaya and Vietnam: Learning to Eat Soup with a Knife. Westport: Praeger, 2002. Pp. xxi, 249. $67.95 (US). Reviewed by Philip E. Catton BRUNA BAGNATO, ed. I Diari di Luca Pietromarchi: Ambasciatore Italiano a Mosca (1958-1961). Florence: Leo S. Olschki, 2002. Pp. 1,446. €49.00, paper. Reviewed by Mario Del Pero NORRIE MACQUEEN. United Nations Peacekeeping in Africa since 1960. London and New York: Longman, 2002. Pp. xiii, 308. £19.99, paper. Reviewed by David Birmingham WILLIAM MALEY. The Afghanistan Wars. Basingstoke and New York: Palgrave Macmillan, 2002. Pp. ix, 340. $65.00 (US), cloth; $19.95 (US), paper. Ludwig W. Adamec AMY BASS. Not the Triumph but the Struggle: The 1968 Olympics and the Making of the Black Athlete. Minneapolis: University of Minnesota Press, 2002. Pp. xxi, 438. $27.95 (US). Reviewed by Geoffrey