Correction to: Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

[This corrects the article DOI: 10.1007/s12288-022-01602-5.].

Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

Romiplostim is a Food and Drug Administration (FDA)-approved therapy for immune thrombocytopenia (ITP). Biosimilar is a biological product that has no clinical meaningful difference from an existing FDA-approved reference product. It has a potential of lowering health-care-related cost. Biosimilar of romiplostim can be made available to patients with ITP at a low cost and can be beneficial in providing the best therapy. Thus, the efficacy and safety of biosimilar romiplostim (ENZ110) was compared with innovator romiplostim (Nplate) with respect to platelet response in patients with chronic ITP. This was a prospective, multicenter, randomized, and double-blind clinical trial. Patients with chronic ITP, aged 18-65 years, were enrolled in a study and were randomized to receive either ENZ110 or Nplate in a 3:1 ratio for a treatment period of 12 weeks, respectively. After completion of the treatment period, the patients were followed-up for one week to evaluate the platelet response and to monitor the adverse events (AEs). Over the duration of 12 weeks, platelet response of > 50 × 109/L was achieved in 85.3% patients treated with ENZ110 and in 75.0% patients treated with Nplate in per protocol population. In intent-to-treat population, 83.8% patients with ENZ110 and 76.9% patients with Nplate achieved a platelet response of > 50 × 109/L. In the ENZ110 group, 111 AEs were recorded in 66.7% patients, while 18 AEs were reported in 61.5% patients in the Nplate group. The study demonstrated non-inferiority with comparable efficacy and safety between biosimilar romiplostim and innovator romiplostim in patients with chronic ITP. Trial registration number and date of registration: CTRI/2019/04/018614.

A Case of Refractory Anemia in Patient of Chronic Kidney Disease and the Challenges in its Management.

Anemia is a common complication of chronic kidney disease (CKD) that has been classically attributed to inadequate production of endogenous erythropoietin.1 Though there are many other common causes of refractory anemia in CKD like iron deficiency, vitamin B12, and folic acid deficiency, noncompliance to dialysis and erythropoietin therapy rare causes like blood loss, bone marrow failure, infections causing aplastic crisis like CMV, parvovirus B19 should be ruled out. Parvovirus has an extreme tropism for erythroid cells and is an uncommon cause of anemia in patients with CKD on maintenance dialysis (MHD) and on erythropoietin.2 Here we are reporting a rare case of refractory anemia in a patient of CKD on MHD secondary to parvovirus-related aplastic crisis. How to cite this article: Gade K, Londhe C, Pednekar S, et al. A Case of Refractory Anemia in Patient of Chronic Kidney Disease and the Challenges in its Management. J Assoc Physicians India 2023;71(10):94-95.

COVID-19 Associated Stroke-A Single Centre Experience.

BACKGROUND AND PURPOSE: Various neurological complications have been reported in association with COVID-19. We report our experience of COVID-19 with stroke at a single center over a period of eight months spanning 1 March to 31 October 2020. METHODS: We recruited all patients admitted to Internal Medicine with an acute stroke, who also tested positive for COVID-19 on RTPCR. We included all stroke cases in our analysis for prediction of in-hospital mortality, and separately analyzed arterial infarcts for vascular territory of ischemic strokes. RESULTS: There were 62 stroke cases among 3923 COVID-19 admissions (incidence 1.6%). Data was available for 58 patients {mean age 52.6 years; age range 17-91; F/M=20/38; 24% (14/58) aged ≤40; 51% (30/58) hypertensive; 36% (21/58) diabetic; 41% (24/58) with O2 saturation <95% at admission; 32/58 (55.17 %) in-hospital mortality}. Among 58 strokes, there were 44 arterial infarcts, seven bleeds, three arterial infarcts with associated cerebral venous sinus thrombosis, two combined infarct and bleed, and two of indeterminate type. Among the total 49 infarcts, Carotid territory was the commonest affected (36/49; 73.5%), followed by vertebrobasilar (7/49; 14.3%) and both (6/49; 12.2%). Concordant arterial block was seen in 61% (19 of 31 infarcts with angiography done). 'Early stroke' (within 48 hours of respiratory symptoms) was seen in 82.7% (48/58) patients. Patients with poor saturation at admission were older (58 vs 49 years) and had more comorbidities and higher mortality (79% vs 38%). Mortality was similar in young strokes and older patients, although the latter required more intense respiratory support. Logistic regression analysis showed that low Glasgow coma score (GCS) and requirement for increasing intensity of respiratory support predicted in-hospital mortality. CONCLUSIONS: We had a 1.6% incidence of COVID-19 related stroke of which the majority were carotid territory infarcts. In-hospital mortality was 55.17%, predicted by low GCS at admission.

Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia: a retrospective cohort study with follow-up from Mumbai, India.

BACKGROUND: Cytokine storm triggered by Severe Coronavirus Disease 2019 (COVID-19) is associated with high mortality. With high Interleukin -6 (IL-6) levels reported in COVID-19 related deaths in China, IL-6 is considered to be the key player in COVID-19 cytokine storm. Tocilizumab, a monoclonal antibody against IL-6 receptor, is used on compassionate grounds for treatment of COVID-19 cytokine storm. The aim of this study was to assess effect of tocilizumab on mortality due to COVID-19 cytokine storm. METHOD: This retrospective, observational study included patients of severe COVID-19 pneumonia with persistent hypoxia (defined as saturation 94% or less on supplemental Oxygen of 15 L per minute through non-rebreathing mask or PaO2/FiO2 ratio of less than 200) who were admitted to a tertiary care center in Mumbai, India, between 31st March to 5th July 2020. In addition to standard care, single Inj. Tocilizumab 400 mg was given intravenously to 151 consecutive COVID-19 patients with persistent hypoxia, from 13th May to 5th July 2020. These 151 patients were retrospectively analysed and compared with historic controls, ie consecutive COVID-19 patients with persistent hypoxia, defined as stated above (N = 118, from our first COVID-19 admission on 31st March to 12th May 2020 i.e., till tocilizumab was available in hospital). Univariate and multivariate Cox regression analysis was performed for identifying predictors of survival. Statistical analysis was performed using IBM SPSS version 26. RESULTS: Out of 269 (151 in tocilizumab group and 118 historic controls) patients studied from 31st March to 5th July 2020, median survival in the tocilizumab group was significantly longer than in the control group; 18 days (95% CI, 11.3 to 24.7) versus 9 days (95% CI, 5.7 to 12.3); log rank p 0.007. On multivariate Cox regression analysis, independent predictors of survival were use of tocilizumab (HR 0.621, 95% CI 0.427-0.903, P 0.013) and higher oxygen saturation. CONCLUSION: Tocilizumab may improve survival in severe COVID-19 pneumonia with persistent hypoxia. Randomised controlled trials on use of tocilizumab as rescue therapy in patients of severe COVID-19 pneumonia with hypoxia (PaO2/FiO2 less than 200) due to hyperinflammatory state, are warranted.

Mortality in Malaria: Intensive Care (MIMIC).

Background: While global incidence of malaria has fallen in last decade, it continues to be an important cause of mortality and morbidity in acutely ill febrile patients. Many patients with complicated malaria require ICU care. In past it was believed that vivax is a benign form of malaria, but now all complications of malaria are reported in vivax. . Aims and Objectives: 1. To find out proportion of patients with plasmodium vivax and plasmodium falciparum malaria requiring treatment in Medical ICU. 2. To compare clinical profile and severity of illness in these patients. 3. To study treatment received including organ support requirement in these patients and compare outcome in patients with vivax and falciparum malaria. Results: During study period total 932 patients were diagnosed as confirmed malaria (601 vivax, 240 falciparum and 91 mixed) and 107 (vivax 74, falciparum 20, mixed 13) required ICU admission. Common symptoms observed apart from fever were, oliguria (48), dyspnea(41), bleeding (29), hemoptysis (15) and petechial rash (13). Mean BUN and creatinine and PT INR of falciparum/mixed malaria patients was significantly higher and HCO3 and pH significantly lower than vivax patients. But PaO2/FiO2 of vivax patient was significantly lower as compared falciparum/mixed patients. There was no significant difference between two groups with regards to requirement of supportive treatment like inotropes (11/70 vs 5/30, p=0.858), mechanical ventilation (28/70 vs 7/30, p=0.17), platelet transfusion (24/70 vs 9/30, p=0.853) and renal replacement therapy (5/70 vs 3/30 p=0.936). Out of 100 patients, 21 patients expired. Mortality in mixed malaria group (4/12, 33.3%) and vivax group ( 16/70, 22.9%) was more as compared to falciparum group (1/18, 5.6%, < 0.05). Conclusions: Incidence of Plasmodium vivax malaria is higher compared to falciparum malaria in hospitalized patients and higher percentage of these need ICU care. Most common complications of malaria are thrombocytopenia followed by renal failure, hepatic dysfunction, ARDS, shock and cerebral dysfunction respectively. Mortality was higher in vivax and mixed malaria compared to falciparum. Higher SOFA score (Sequential organ failure assessment score), lower GCS score (Glasgow coma scale), hypotension, ARDS and metabolic acidosis are predictors of mortality.

Life-threatening Medical Complications Due to Ovarian Hyperstimulation Syndrome: A Hidden Etiology.

Ovarian hyperstimulation syndrome is usually an iatrogenic complication in women taking ovulation induction medications during assisted reproduction. We hereby report the case of a 25 years old female who presented with hypertension, polyserositis with tense ascites and large cystic ovaries. She developed sigmoid and transverse sinus thrombosis. She had undergone a clandestine ovulation induction therapy as a commercial ovum donor. She fitted in severe category of ovarian hyperstimulation syndrome.

Reversible steatohepatosis in a young boy with brittle type 1 diabetes mellitus: mauriac syndrome.

A 14-year-old male, diagnosed case of type 1 diabetes mellitus since 1 year, presented with uncontrolled blood glucose levels, non-compliance with insulin therapy and recurrent admissions with diabetic ketoacidosis. His blood glucose levels were difficult to control with wide fluctuations in insulin requirement. He had absent secondary sexual characteristics and hepatomegaly. Liver biopsy showed macrovesicularsteatosis without fibrosis or inflammation. Many glycogenated nuclei were present. He was started on intensive insulin therapy, whereby he showed subsequent regression of hepatomegaly and onset of pubertal spurt.

Renal tubular acidosis due to Wilson's disease presenting as metabolic bone disease.

Two sisters presented with lower limb deformity and difficulty in walking without support. Both had short stature; however, neurodevelopment and secondary sexual characters were normal. Abdominal examination revealed splenomegaly and ophthalmic examination showed presence of Kayser-Fleischer (K-F) rings. Diagnosis of Wilson's disease was confirmed with low serum copper and ceruloplasmin levels. Further investigations revealed urinary acidification defect with hypercalciuria pointing towards distal renal tubular acidosis. Both patients were started on copper chelation therapy and showed gradual radiographic improvement in osteopaenia.

Acrocallosal syndrome in a young hypertensive male.

Acrocallosal syndrome is an extremely rare genetic disorder with autosomal recessive inheritance. It is characterised by moderate to severe mental retardation, hypotonia, agenesis of the corpus callosum and preaxial polydactyly involving both feet and the facial features like broad forehead and hypertelorism. The authors report a case of a young hypertensive male who presented with unprovoked seizures for the first time who had multiple craniofacial, digital dysmorphic features with moderate mental retardation. The diagnosis of acrocallosal syndrome was arrived at after neuroimaging showed agenesis of corpus callosum with interhemispheric cysts.

Xanthogranulomatous pyelonephritis in a young postpartal female.

Xanthogranulomatous pyelonephritis (XGP) is a rare chronic inflammatory disorder of the kidney characterised by an infectious phlegmon arising in the renal parenchyma. It is seen in patients who have urolithiasis, urinary tract infection and immunocompromised status. The clinical presentation is variable and renal neoplasm is considered as a differential due to its characteristic extrarenal visceral invasion. The treatment is almost universally extirpative and can pose a formidable challenge to the treating physician and surgeon. The authors report a rare case of XGP in a postpartal woman who presented with multiple visceral abscesses whose diagnosis was arrived on histopathological examination.