Emphysematous pyelonephritis in renal allograft recipients is a rare but serious complication. The management of this entity is a subject of controversy in live related donor programs where the absence of a second donor is a key factor influencing surgical removal of the graft. We present a case of emphysematous pyelonephritis in a renal allograft recipient managed successfully with medical therapy alone.

Introduction Emphysematous pyelonephritis (EPN) is a deadly disease due to its associated morbidity and mortality. Attempts have been made to identify predictors of severity, mortality and need for nephrectomy in EPN with little success. Methods We conducted an ambispective study of EPN patients between March 2014 and September 2019. Retrospective data were collected which included age, sex, comorbidities, symptoms, signs, laboratory investigations including imaging, need for dialysis, management and any complications. All patients were then followed prospectively for renal dynamic scan, stone surgery or nephrectomy. Univariate analysis was performed to identify factors affecting mortality and need for elective nephrectomy. Results In total, 112 patients were included. Mean patient age was 50.01 years, 55% were female and 5% had bilateral involvement. Fever and flank pain were the most common symptoms. Diabetes was seen in 75% of cases and 30% of cases required haemodialysis at initial presentation. About 60% of patients improved with pigtail drainage. Need for nephrectomy was greater in Huang–Tseng stage 3a (14.8%). Huang–Tseng stages 3b and 4 had higher mortality rates (25%) than the other stages (2.2%). Twelve of 99 patients had non functional kidney on follow-up and underwent elective nephrectomy. Low platelet counts, high body mass index, septic shock, dialysis and higher Huang–Tseng stage were found to be predictive of mortality and renal parenchymal thickness on computed tomography scan was predictive of follow-up nephrectomy. Conclusions Thrombocytopaenia, high body mass index, septic shock, haemodialysis and higher Huang–Tseng stage are predictors of mortality and renal parenchymal thickness <5mm is a predictor of poor salvage of affected kidney on follow-up.

At two years, DFIS was associated with cost savings (£6,954 per-participant).Conclusions: Although OS just fell short of overall defined NI using this rigorous approach, probably due to fewer than expected events, QALY NI was demonstrated and a DFIS was seen to be acceptable to patients and clinicians. DFIS also appeared to be highly cost-effective compared to CCS.

ObjectivesThe pathophysiology of SARS-Cov-2 is characterized by inflammation, immune dysregulation, coagulopathy, and endothelial dysfunction. No single therapeutic agent can target all these pathophysiologic substrates. Moreover, the current therapies are not fully effective in reducing mortality in moderate and severe disease. Hence, we aim to evaluate the combination of drugs (aspirin, atorvastatin, and nicorandil) with anti-inflammatory, antithrombotic, immunomodulatory, and vasodilator properties as adjuvant therapy in covid- 19.Trial designSingle-centre, prospective, two-arm parallel design, open-label randomized control superiority trial. ParticipantsThe study will be conducted at the covid centre of Dr. Rajendra Prasad Government Medical College Tanda Kangra, Himachal Pradesh, India. All SARS-CoV-2 infected patients requiring admission to the study centre will be screened for the trial. All patients >18years who are RT-PCR/RAT positive for SARS-CoV-2 infection with pneumonia but without ARDS at presentation (presence of clinical features of dyspnoea hypoxia, fever, cough, spo2 <94% on room air and respiratory rate >24/minute) requiring hospital admission and consenting to participate in the trial will be included.Patients with documented significant liver disease/dysfunction (AST/ALT > 240), myopathy and rhabdomyolysis (CPK > 5x normal), allergy or intolerance to statins, allergy or intolerance to aspirin, patients taking medications with significant interaction with statins, prior statin use (within 30 days), prior aspirin use (within 30 days), history of active GI bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, patient unable to take oral or nasogastric medications, patients in altered mental status, shock, acute renal failure, acute coronary syndrome, sepsis and ARDS at presentation will be excluded. Intervention and comparatorAfter randomization, participants in the intervention group will receive aspirin, atorvastatin, and nicorandil. Atorvastatin will be prescribed as 40 mg starting dose followed by 40 mg oral tablets once daily for ten days or till hospital discharge whichever is later. Aspirin dose will be 325 starting dose followed by 75 mg once daily for ten days or till hospital discharge whichever is later. Nicorandil will be given as 10 mg starting dose followed by 5mg twice daily ten days or till hospital discharge whichever is later. All patients in the intervention and control group will receive a standard of care for covid management as per national guidelines. All patients will receive symptomatic treatment with antipyretics, adequate hydration, anticoagulation with low molecular weight heparin, intravenous remdesivir, corticosteroids (intravenous dexamethasone for 5 days or more duration if oxygen requirement increasing or inflammatory markers are raised), and oxygen support. Patients will receive treatment for comorbid conditions as per guidelines.Main outcomesThe patients will be followed up for outcomes during the hospital stay or for ten days whichever is longer. The primary outcome will be in-hospital mortality. Any progression to ARDS, shock, acute kidney injury, impaired consciousness, length of hospital stay, length of mechanical ventilation (invasive plus non-invasive) will be secondary outcomes. Changes in serum markers (CRP, D –dimer, S ferritin) will be other secondary outcomes. The safety endpoints will be hepatotoxicity (ALT/AST > 3x ULN; hyperbilirubinemia), myalgia—muscle ache, or weakness without creatine kinase (CK) elevation, myositis—muscle symptoms with increased CK levels (3-10) ULN, rhabdomyolysis—muscle symptoms with marked CK elevation (typically substantially greater than 10 times the upper limit of normal [ULN]) and with creatinine elevation (usually with brown urine and urinary myoglobin) observed during the hospital stay. RandomizationComputer-generated block randomization will be used to randomize the participants in a 1:1 ratio to the active intervention group A (Aspirin, Atorvastatin, Nicorandil) plus conventional therapy and control group B conventional therapy only. Blinding (masking)The study will be an open-label trial. Numbers to be randomized (sample size)A total of 396 patients will participate in this study, which is randomly divided with 198 participants in each group.Trial statusThe first version of the protocol was approved by the institutional ethical committee on 1st February 2021, IEC /006/2021. The recruitment started on 8/4/2021 and will continue until 08/07/2021. A total of 281 patients have been enrolled till 21/5/2021.Trial registrationThe trial has been prospectively registered in Clinical Trial Registry – India (ICMR- NIMS): CTRI/2021/04/032648 [Registered on: 08/04/2021].Full protocolThe full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported under the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Objectives The pathophysiology of SARS-Cov-2 is characterized by inflammation, immune dysregulation, coagulopathy, and endothelial dysfunction. No single therapeutic agent can target all these pathophysiologic substrates. Moreover, the current therapies are not fully effective in reducing mortality in moderate and severe disease. Hence, we aim to evaluate the combination of drugs (aspirin, atorvastatin, and nicorandil) with anti-inflammatory, antithrombotic, immunomodulatory, and vasodilator properties as adjuvant therapy in covid- 19. Trial design Single-centre, prospective, two-arm parallel design, open-label randomized control superiority trial. Participants The study will be conducted at the covid centre of Dr. Rajendra Prasad Government Medical College Tanda Kangra, Himachal Pradesh, India. All SARS-CoV-2 infected patients requiring admission to the study centre will be screened for the trial. All patients >18years who are RT-PCR/RAT positive for SARS-CoV-2 infection with pneumonia but without ARDS at presentation (presence of clinical features of dyspnoea hypoxia, fever, cough, spo2 <94% on room air and respiratory rate >24/minute) requiring hospital admission and consenting to participate in the trial will be included. Patients with documented significant liver disease/dysfunction (AST/ALT > 240), myopathy and rhabdomyolysis (CPK > 5x normal), allergy or intolerance to statins, allergy or intolerance to aspirin, patients taking medications with significant interaction with statins, prior statin use (within 30 days), prior aspirin use (within 30 days), history of active GI bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, patient unable to take oral or nasogastric medications, patients in altered mental status, shock, acute renal failure, acute coronary syndrome, sepsis and ARDS at presentation will be excluded. Intervention and comparator After randomization, participants in the intervention group will receive aspirin, atorvastatin, and nicorandil (Fig. 1). Atorvastatin will be prescribed as 40 mg starting dose followed by 40 mg oral tablets once daily for ten days or till hospital discharge whichever is later. Aspirin dose will be 325 starting dose followed by 75 mg once daily for ten days or till hospital discharge whichever is later. Nicorandil will be given as 10 mg starting dose followed by 5mg twice daily ten days or till hospital discharge whichever is later. All patients in the intervention and control group will receive a standard of care for covid management as per national guidelines. All patients will receive symptomatic treatment with antipyretics, adequate hydration, anticoagulation with low molecular weight heparin, intravenous remdesivir, corticosteroids (intravenous dexamethasone for 5 days or more duration if oxygen requirement increasing or inflammatory markers are raised), and oxygen support. Patients will receive treatment for comorbid conditions as per guidelines. Main outcomes The patients will be followed up for outcomes during the hospital stay or for ten days whichever is longer. The primary outcome will be in-hospital mortality. Any progression to ARDS, shock, acute kidney injury, impaired consciousness, length of hospital stay, length of mechanical ventilation (invasive plus non-invasive) will be secondary outcomes. Changes in serum markers (CRP, D –dimer, S ferritin) will be other secondary outcomes. The safety endpoints will be hepatotoxicity (ALT/AST > 3x ULN; hyperbilirubinemia), myalgia—muscle ache, or weakness without creatine kinase (CK) elevation, myositis—muscle symptoms with increased CK levels (3-10) ULN, rhabdomyolysis—muscle symptoms with marked CK elevation (typically substantially greater than 10 times the upper limit of normal [ULN]) and with creatinine elevation (usually with brown urine and urinary myoglobin) observed during the hospital stay. Randomization Computer-generated block randomization will be used to randomize the participants in a 1:1 ratio to the active intervention group A (Aspirin, Atorvastatin, Nicorandil) plus conventional therapy and control group B conventional therapy only. Blinding (masking) The study will be an open-label trial. Numbers to be randomized (sample size) A total of 396 patients will participate in this study, which is randomly divided with 198 participants in each group. Trial status The first version of the protocol was approved by the institutional ethical committee on 1st February 2021, IEC /006/2021. The recruitment started on 8/4/2021 and will continue until 08/07/2021. A total of 281 patients have been enrolled till 21/5/2021. Trial registration The trial has been prospectively registered in Clinical Trial Registry – India (ICMR- NIMS): CTRI/2021/04/032648 [Registered on: 8 April 2021]. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported under the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.