The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence.Methods: Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs.Results: In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence.Conclusion: This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.

Forty-three patients averaging 28.2 (range 16-74) years with open fractures of the lower limbs were studied prospectively for 40 weeks using anthropometrical, biochemical and haematological parameters to ascertain their relationship to wound healing following injury. Nearly half (21/43) of the patients were malnourished at admission and the number increased to 22 a week after injury. Dietary advice and better food intake improved nutritional status with only 13 patients remaining malnourished at the 40th week. Wound healing was earlier when creatinine-height index was normal throughout the course of treatment and was delayed when serum albumin level was low.Résumé Nous avons suivi prospectivement, pendant quarante semaines, 43 malades avec des fractures combinées du membre inférieur en utilisant des paramètres anthropométrique, biochimique et hématologique pour étudier leur relation avec la cicatrisation des parties molles après l'accident. Prés de la moitié des patients (21/43) étaient considérés comme malnutris à leur admission. Les conseils diététiques et une meilleure prise de la nourriture ont amélioré le statut nutritionnel avec seulement treize malades dans le groupe malnutris à la quarantième semaine. La guérison des blessures était plus précoce quand l'index de créatinine était normal durant le cours du traitement et a été retardée quand le niveau de sérum albumine était bas.

MDR1 3435C>T gene polymorphism influences the clinical phenotype and adverse events to MTX in the South Indian cohort of patients with RA.

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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple etiological factors. Mannose-binding lectin (MBL) plays a key role in innate immunity by activating antibody-independent lectin complement pathway, opsonisation, phagocytosis, and immune complex (IC) clearance. Genetic polymorphisms in the promoter and coding regions of MBL gene affect the circulatory levels and biological activity of MBL. Defects in MBL can lead to defective opsonisation and, hence, hamper clearance of apoptotic debris, the persistence of which can drive autoantibody formation in lupus. The exon1 variants at codon 52, 54, and 57 have been reported to augment the risk of SLE in different ethnic populations. Three hundred South Indian Tamil patients with SLE and 460 age-, sex-, and ethnicity-matched controls were genotyped for three polymorphisms at codon 52, 54, and 57 in exon1 of MBL gene by Taqman real-time PCR. The three polymorphisms in exon1 of MBL were observed not to confer risk of developing SLE. However, MBL codon 54 rs1800450 polymorphism was associated with the development of medium vessel vasculitis and gangrene (OR-2.29, CI 95% 1.08-4.83, p = 0.02), whereas, the ancestral allele G conferred protection (OR-0.44, CI 95% 0.21-0.93, p = 0.02). Genetic variants in the exon1 of MBL gene per se are not risk factors for SLE in South Indian Tamils. However, the association of codon 54 (rs1800450) with medium vessel vasculitis suggests that it may be a genetic modifier of clinical phenotype in SLE.

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Background Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with predominant involvement of exocrine glands in middle aged females. It may involve extra-glandular tissues such as lung, liver, kidney, pancreas, skin, and central nervous system. Clinically significant renal involvement in pSS is rare and interstitial nephritis is the commonest histopathological finding1. The resulting tubular defects may present with failure to concentrate urine (hyposthenuria) and type I (distal) renal tubular acidosis characterized by hyperchloremic metabolic acidosis and hypokalemia. We describe a series of 15 cases of pSS who presented with hypokalemic periodic paralysis as the initial manifestation. Their clinical features; biochemical and immunological parameters are compared and contrasted with those without hypokalemic weakness. Objectives To explore the clinical, biochemical, serologic features, and therapeutic responses in Primary Sjogrens syndrome (pSS) patients who presented with hypokalemic paralysis as the initial manifestation. Methods Sixty patients of pSS (diagnosis based on modified European-American classification criteria) are on our follow up from November 2009 to August 2012. A few of these patients were diagnosed following admission to emergency services with hypokalemic paralysis. They were compared for differences in clinical features, biochemistry and serological parameters with pSS patients without hypokalemic paralysis. Results Symptomatic hypokalemia was the presenting symptom in 15 out of 60 (25%) primary SS. All patients in the hypokalemic paralysis group were females and with a lower age of onset (27.8±8.3 vs 38.85±11.5 yrs). Six of 15 (40%) patients did not have the classical sicca symptoms. All patients with hypokalemic paralysis had biochemical features of distal renal tubular acidosis and high titers of anti SSA antibody. During a mean follow up of sixteen months, only two patient developed relapse of hypokalemic weakness following stoppage of potassium supplements. Conclusions There exists a distinct subset of pSS who present with onset at younger age, distal RTA, hypokalemic paralysis and high titres of anti SSA antibody sometimes even without characteristic exocrinopathy. Genetic analysis may help in further characterization of these patients. Therefore, all young females presenting with hypokalemic paralysis should be investigated for underlying pSS. References Andreas V. Goules, Ioanna P. Tatouli, Haralampos M. Moutsopoulos, Athanasios G. Tzioufas. Clinically Significant Renal Involvement in Primary Sjögren's Syndrome. Clinical Presentation and Outcome. Arthritis & Rheumatism.2013 Nov;65(11):2945–53 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1739

The association of malignancy with autoimmune rheumatic diseases has been a subject of investigation. It has been shown that there is increased risk of malignancies, mainly non-Hodgkin lymphoma, in patients with autoimmune disorders. There is scarcity of data about malignancy in juvenile idiopathic arthritis (JIA). We report the occurrence of anaplastic large cell lymphoma in a patient with systemic onset juvenile idiopathic arthritis treated with low dose methotrexate (MTX). A relationship between MTX treatment and the occurrence of lymphoma in autoimmune diseases has been suggested. The hypothesis that MTX has a role in the aetiology of lymphoproliferative disorders is supported by the observation of spontaneous remission of lymphoma in few cases on cessation of MTX therapy. However, systemic onset juvenile idiopathic arthritis patients receiving MTX must be periodically examined for the development of lymphoproliferative disorder especially if the disease is difficult to control or patient develop new symptoms on therapy.