Sir Ganga Ram Hospital

. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

The PROCESS Guidelines were first published in 2016 and were last updated in 2018. They provide a structure for reporting surgical case series in order to increase reporting robustness and transparency, and are used and endorsed by authors, journal editors and reviewers alike. In order to drive forwards reporting quality, they must be kept up to date. As such, we have updated these guidelines via a DELPHI consensus exercise. The updated guidelines were produced via a DELPHI consensus exercise. Members from the previous DELPHI group were again invited, alongside editorial board members and peer reviewers of the International Journal of Surgery and the International Journal of Surgery Case Reports. An online survey was completed by this expert group to indicate their agreement with proposed changes to the checklist items. A total of 53 surgical experts agreed to participate and 49 (92%) completed the survey. The responses and suggested modifications were incorporated into the previous 2018 guidelines. There was a high degree of agreement amongst the PROCESS Group, with all but one of the PROCESS items receiving over 70% of scores ranging 7–9. A DELPHI consensus exercise was completed and an updated and improved PROCESS Checklist is now presented. • This was a DELPHI consensus exercise to update the PROCESS guidelines. • Of the invited surgical experts, 49 (92%) completed the survey. There was a high level of agreement in the PROCESS Group. • The survey responses were incorporated as modifications and an improved PROCESS Checklist is now presented for use.

BACKGROUND: Among the chronic rheumatic diseases, hip and knee osteoarthritis (OA) is the most prevalent and is a leading cause of pain and disability in most countries worldwide. Its prevalence increases with age and generally affects women more frequently than men. OA is strongly associated with aging and heavy physical occupational activity, a required livelihood for many people living in rural communities in developing countries. Determining region-specific OA prevalence and risk factor profiles will provide important information for planning future cost effective preventive strategies and health care services. MATERIALS AND METHODS: The study was a community based cross sectional study to find out the prevalence of primary knee OA in India which has a population of 1.252 billion. The study was done across five sites in India. Each site was further divided into big city, small city, town, and village. The total sample size was 5000 subjects. Tools consisted of a structured questionnaire and plain skiagrams for confirmation of OA. Diagnosis was done using Kellgren and Lawrence scale for osteoarthritis. RESULTS: = 0.001). CONCLUSIONS: There is scarcity of studies done in India which has varied socio geographical background and communities. We conducted this study for analyzing the current prevalence of OA in different locations. This study has evidenced a large percentage of population as borderline OA; therefore, it depends mainly on the prevention of modifiable risk factors to preserve at ease movement in elderly population through awareness programs.

BACKGROUND: There are no national data on the magnitude and pattern of chronic kidney disease (CKD) in India. The Indian CKD Registry documents the demographics, etiological spectrum, practice patterns, variations and special characteristics. METHODS: Data was collected for this cross-sectional study in a standardized format according to predetermined criteria. Of the 52,273 adult patients, 35.5%, 27.9%, 25.6% and 11% patients came from South, North, West and East zones respectively. RESULTS: The mean age was 50.1 ± 14.6 years, with M:F ratio of 70:30. Patients from North Zone were younger and those from the East Zone older. Diabetic nephropathy was the commonest cause (31%), followed by CKD of undetermined etiology (16%), chronic glomerulonephritis (14%) and hypertensive nephrosclerosis (13%). About 48% cases presented in Stage V; they were younger than those in Stages III-IV. Diabetic nephropathy patients were older, more likely to present in earlier stages of CKD and had a higher frequency of males; whereas those with CKD of unexplained etiology were younger, had more females and more frequently presented in Stage V. Patients in lower income groups had more advanced CKD at presentation. Patients presenting to public sector hospitals were poorer, younger, and more frequently had CKD of unknown etiology. CONCLUSIONS: This report confirms the emergence of diabetic nephropathy as the pre-eminent cause in India. Patients with CKD of unknown etiology are younger, poorer and more likely to present with advanced CKD. There were some geographic variations.

OBJECTIVE: To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA). METHODS: In this multinational, multicenter study, pediatric rheumatologists and hemato-oncologists entered patient data collected retrospectively into a web-based database. RESULTS: A total of 362 patients, 22% of whom had MAS at the onset of systemic JIA, were included in the study by 95 investigators from 33 countries. The most frequent clinical manifestations were fever (96%), hepatomegaly (70%), and splenomegaly (58%). Central nervous system dysfunction and hemorrhages were recorded in 35% and 20% of the patients, respectively. Platelet count and liver transaminase, ferritin, lactate dehydrogenase, triglyceride, and d-dimer levels were the sole laboratory biomarkers showing a percentage change of >50% between the pre-MAS visit and MAS onset. Evidence of macrophage hemophagocytosis was found in 60% of the patients who underwent bone marrow aspiration. MAS occurred most frequently in the setting of active underlying disease, in the absence of a specific trigger. Nearly all patients were given corticosteroids, and 61% received cyclosporine. Biologic medications and etoposide were given to 15% and 12% of the patients, respectively. Approximately one-third of the patients required admission to the intensive care unit (ICU), and the mortality rate was 8%. CONCLUSION: This study provides information on the clinical spectrum and current management of systemic JIA-associated MAS through the analysis of a very large patient sample. MAS remains a serious condition, as a sizeable proportion of patients required admission to the ICU or died.

Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India's second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05). Conclusion: : Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

BACKGROUND: There is a rising incidence of chronic kidney disease that is likely to pose major problems for both healthcare and the economy in future years. In India, it has been recently estimated that the age-adjusted incidence rate of ESRD to be 229 per million population (pmp), and >100,000 new patients enter renal replacement programs annually. METHODS: We cross-sectionally screened 6120 Indian subjects from 13 academic and private medical centers all over India. We obtained personal and medical history data through a specifically designed questionnaire. Blood and urine samples were collected. RESULTS: The total cohort included in this analysis is 5588 subjects. The mean ± SD age of all participants was 45.22 ± 15.2 years (range 18-98 years) and 55.1% of them were males and 44.9% were females. The overall prevalence of CKD in the SEEK-India cohort was 17.2% with a mean eGFR of 84.27 ± 76.46 versus 116.94 ± 44.65 mL/min/1.73 m2 in non-CKD group while 79.5% in the CKD group had proteinuria. Prevalence of CKD stages 1, 2, 3, 4 and 5 was 7%, 4.3%, 4.3%, 0.8% and 0.8%, respectively. CONCLUSION: The prevalence of CKD was observed to be 17.2% with ~6% have CKD stage 3 or worse. CKD risk factors were similar to those reported in earlier studies.It should be stressed to all primary care physicians taking care of hypertensive and diabetic patients to screen for early kidney damage. Early intervention may retard the progression of kidney disease. Planning for the preventive health policies and allocation of more resources for the treatment of CKD/ESRD patients are imperative in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

Better classification of headache disorders enables better headache research, understanding of headache, communication, and, ultimately, management of a set of disabling neurological disorders.

Protein aggregation is the hallmark of several neurodegenerative disorders. These protein aggregation (fibrillization) disorders are also known as amyloid disorders. The mechanism of protein aggregation involves conformation switch of the native protein, oligomer formation leading to protofibrils and finally mature fibrils. Mature fibrils have long been considered as the cause of disease pathogenesis; however, recent evidences suggest oligomeric intermediates formed during fibrillization to be toxic. In this review, we have tried to address the ongoing debate for these toxic amyloid species. We did an extensive literature search and collated information from Pubmed (http://www.ncbi.nlm.nih.gov) and Google search using various permutations and combinations of the following keywords: Neurodegeneration, amyloid disorders, protein aggregation, fibrils, oligomers, toxicity, Alzheimer's Disease, Parkinson's Disease. We describe different instances showing the toxicity of mature fibrils as well as oligomers in Alzheimer's Disease and Parkinson's Disease. Distinct structural framework and morphology of amyloid oligomers suggests difference in toxic effect between oligomers and fibrils. We highlight the difference in structure and proposed toxicity pathways for fibrils and oligomers. We also highlight the evidences indicating that intermediary oligomeric species can act as potential diagnostic biomarker. Since the formation of these toxic species follow a common structural switch among various amyloid disorders, the protein aggregation events can be targeted for developing broad-range therapeutics. The therapeutic trials based on the understanding of different protein conformers (monomers, oligomers, protofibrils and fibrils) in amyloid cascade are also described.

BACKGROUND AND STUDY AIMS: The aim of this prospective study was to compare fine-needle aspiration guided by endoscopic ultrasonography (EUS-FNA) using 25-gauge and 22-gauge needles with the EUS-guided 19-gauge Trucut needle biopsy (EUS-TNB) in patients with solid pancreatic mass. PATIENTS AND METHODS: Twenty-four consecutive patients with pancreatic mass underwent biopsies by both EUS-FNA and EUS-TNB. Three needles were compared with respect to technical success rate, tissue size obtained, overall diagnostic accuracy and accuracy for histological and cytological diagnosis. RESULTS: The 25-gauge EUS-FNA was technically easier and obtained superior overall diagnostic accuracy than the 22-gauge and Trucut needles, especially in lesions of the pancreas head and uncinate process. Overall accuracy for the 25-gauge, 22-gauge and Trucut needle was 91.7%, 79.7% and 54.1%, respectively. Accuracy for cytological diagnosis irrespective the site of lesions with 25-gauge, 22-gauge and Trucut needles was 91.7%, 75.0%, and 45.8%, respectively. For uncinate masses, it was 100%, 33.3%, and 0.0%, respectively. These differences were significant. Among technically successful patients, the accuracy for histological diagnosis using the 25-gauge was significantly inferior (P < 0.05) to 22-gauge and Trucut needles and the rates were 45.8%, 78.9% and 83.3%. CONCLUSIONS: The 25-gauge FNA needle was significantly superior in terms of technical success rate and overall diagnostic accuracy, especially for the head and uncinate lesions, compared to the 22-gauge and Trucut needles and could be considered 'the best choice needle for cytological diagnosis' of solid pancreatic lesions. If histological diagnosis is required, the 22-gauge FNA needle and Trucut needle may be advantageous for use in head/uncinate and body/tail lesions, respectively.

OBJECTIVES: Screening for esophageal varices (EV) is recommended in patients with cirrhosis. Noninvasive tests had shown varying sensitivity (Se) and specificity (Sp) for predicting EV. Splenomegaly is a common finding in liver cirrhosis because of portal and splenic congestion. These changes can be quantified by transient elastography; hence, the aim of this study was to investigate the utility of spleen stiffness (SS) in evaluating EV in comparison with other noninvasive tests. METHODS: We measured SS and liver stiffness (LS) by using FibroScan in 200 consecutive cirrhotic patients who met the inclusion criteria. Patients were also assessed by hepatic venous pressure gradient (HVPG), upper gastrointestinal endoscopy, LS-spleen diameter to platelet ratio score (LSPS), and platelet count to spleen diameter ratio (PSR). RESULTS: Of 200 patients enrolled, 174 patients had valid LS and SS measurement, and 124 (71%) patients had EV (small, n=46 and large n=78). There was a significant difference in median LS (51.4 vs. 23.9 kPa, P=0.001), SS (54 vs. 32 kPa, P=0.001), LSPS (6.1 vs. 2.5, P=0.001), and PSR (812 vs. 1,165, P=0.001) between patients with EV and those without EV. LS ≥27.3 kPa had an Se of 91%, Sp of 72%, positive predictive value (PPV) of 89%, negative predictive value (NPV) of 76%, and a diagnostic accuracy of 86% in predicting EV. LSPS ≥3.09 had Se and Sp of 89% and 76%, respectively, and a PSR cutoff value of 909 or less had Se of 64%, Sp of 76%, and diagnostic accuracy of 68% in predicting EV. SS ≥40.8 kPa had Se (94%), Sp (76%), PPV (91%), NPV (84%), and diagnostic accuracy of 86% for predicting EV. SS was significantly higher in patients who had large varices (56 vs. 49 kPa, P=0.001) and variceal bleed (58 vs. 50.2 kPa, P=0.001). Combining LS+SS (27.3+40.8 kPa) had Se of 90%, Sp 90%, PPV 96%, NPV 79%, and a diagnostic accuracy of 90%. HVPG (n=52) showed significant correlation with SS (r=0.433, P=0.001), LSPS (r=0.335, P=0.01), and PSR (r=-0.270, P=0.05), but not with LS (r=0.178, P=0.20). CONCLUSIONS: Measurement of SS can be used for noninvasive assessment of EV and can differentiate large vs. small varices and nonbleeder vs. bleeder.

PURPOSE: A retrospective study was carried out of patients who underwent laparoscopic ventral abdominal wall hernia repair (excluding groin hernias) between January 1994 and January 1999. PATIENTS AND METHODS: Laparoscopic ventral hernia repair was performed on 202 patients for defects ranging from 1.5 cm to 12 cm in diameter. Of these, 35 patients had multiple hernial defects. After reduction of the hernial contents and adhesiolysis, a polypropylene mesh was used intraperitoneally in all patients, such that there was a margin of at least 3 cm from the edge of the defect as well as the previous scar. RESULTS: The mean operating time decreased from 90 minutes in the initial 3 years to 50 minutes in the last 2 years. Postoperatively, the mean hospital stay was 1.8 days. Patients complained of somatic abdominal pain at the site of mesh insertion for a mean of 7 days. There were two postoperative hernia recurrences at a mean follow-up of 2.9 years. The incidence of seroma formation postoperatively was 32% in the first 3 years but declined to 18% subsequently with postoperative abdominal-wall pressure dressings. There were no postoperative sequelae related to bowel adhesions. Negligible wound sepsis (superficial wound infection in five patients), decreased morbidity, and all the other advantages of a minimally invasive surgical approach were evident in this group of patients. CONCLUSION: These promising early results need to be confirmed by a prospective controlled trial, especially recurrence rates and incidence of postoperative adhesions.

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple café-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P < 0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients.

Prolactin (PRL) is an anterior pituitary hormone which has its principle physiological action in initiation and maintenance of lactation. In human reproduction, pathological hyperprolactinemia most commonly presents as an ovulatory disorder and is often associated with secondary amenorrhea or oligomenorrhea. Galactorrhea, a typical symptom of hyperprolactinemia, occurs in less than half the cases. Out of the causes of hyperprolactinemia, pituitary tumors may be responsible for almost 50% of cases and need to be investigated especially in the absence of history of drug induced hyperprolactinemia. In women with hyperprolactinemic amenorrhea one important consequence of estrogen deficiency is osteoporosis, which deserves specific therapeutic consideration. Problem in diagnosing and treating hyperprolactinemia is the occurrence of the 'big big molecule of prolactin' that is biologically inactive (called macroprolactinemia), but detected by the same radioimmunoassay as the biologically active prolactin. This may explain many cases of very high prolactin levels sometimes found in normally ovulating women and do not require any treatment. Dopamine agonist is the mainstay of treatment. However, presence of a pituitary macroadenoma may require surgical or radiological management.

OBJECTIVES: To describe antimicrobial susceptibility among bacterial isolates associated with hospital infections collected from 266 centres in Asia/Pacific Rim (n = 1,947), North America (n = 24,283), Latin America (n = 1,957) and Europe (n = 8,796). METHODS: Isolates were collected from blood, respiratory tract, urine, skin, wound, body fluids and other defined sources between January 2004 and August 2006. Only one isolate per patient was accepted. In vitro MICs for the isolates were determined according to the CLSI (formerly NCCLS) guidelines. RESULTS: Key organisms collected were Acinetobacter baumannii (n = 2,902), Enterobacter spp. (n = 5,731), Escherichia coli (n = 6,504), Klebsiella pneumoniae (n = 4,916), Pseudomonas aeruginosa (n = 5,128), Serratia marcescens (n = 2,313), Enterococcus faecalis (n = 2,701), Enterococcus faecium (n = 1,035) and Staphylococcus aureus (n = 5,753). Rates of methicillin resistance among S. aureus and of vancomycin resistance among enterococci were highest in North America (2,016/3,809, 52.9% and 571/2,544, 22.4%, respectively) and lowest in Europe (337/1,340, 25.1% and 36/916, 3.9%, respectively). Tigecycline was the only antimicrobial to maintain activity against all Gram-positive isolates (MIC(90) values of <or=0.25 mg/L). Overall, tigecycline and imipenem were the most active (>93% susceptibility in all regions) antimicrobials against the Gram-negative species, except for A. baumannii and P. aeruginosa. Piperacillin/tazobactam and amikacin were the most active against P. aeruginosa. Extended-spectrum beta-lactamase producers among K. pneumoniae occurred most frequently in Latin America (124/282, 44.0%). CONCLUSIONS: Tigecycline is a novel broad-spectrum antimicrobial that is active against the common organisms associated with infections.

In January 2005, the government of India enacted a new rule that allows foreign pharmaceutical companies and other interested parties to conduct trials of new drugs in India at the same time that trials of the same phase are being conducted in other countries. This new rule supersedes a directive of India's Drugs and Cosmetics Rules that required a “phase lag” between India and the rest of the world. According to the old rule, if a phase 3 study had been completed elsewhere, only a phase 2 study was permitted in India. Even under the new rule, phase 1 trials . . .

Purpose: Critically ill coronavirus disease 2019 (COVID-19) patients need hospitalization which increases their risk of acquiring secondary bacterial and fungal infections. The practice of empiric antimicrobial prescription, due to limited diagnostic capabilities of many hospitals, has the potential to escalate an already worrisome antimicrobial resistance (AMR) situation in India. This study reports the prevalence and profiles of secondary infections (SIs) and clinical outcomes in hospitalized COVID-19 patients in India. Patients and Methods: A retrospective study of secondary infections in patients admitted in intensive care units (ICUs) and wards of ten hospitals of the Indian Council of Medical Research (ICMR) AMR surveillance network, between June and August 2020, was undertaken. The demographic data, time of infection after admission, microbiological and antimicrobial resistance data of secondary infections, and clinical outcome data of the admitted COVID-19 patients were collated. Results: Out of 17,534 admitted patients, 3.6% of patients developed secondary bacterial or fungal infections. The mortality among patients who developed secondary infections was 56.7% against an overall mortality of 10.6% in total admitted COVID-19 patients. Gram-negative bacteria were isolated from 78% of patients. Klebsiella pneumoniae (29%) was the predominant pathogen, followed by Acinetobacter baumannii (21%). Thirty-five percent of patients reported polymicrobial infections, including fungal infections. High levels of carbapenem resistance was seen in A. baumannii (92.6%) followed by K. pneumoniae (72.8%). Conclusion: Predominance of Gram-negative pathogens in COVID-19 patients coupled with high rates of resistance to higher generation antimicrobials is an alarming finding. A high rate of mortality in patients with secondary infections warrants extra caution to improve the infection control practices and practice of antimicrobial stewardship interventions not only to save patient lives but also prevent selection of drug-resistant infections, to which the current situation is very conducive. Keywords: COVID-19, secondary infections, antimicrobial resistance, hospital acquired infections, antibiotics

Heme oxygenase-1 (HO-1) is a stress-induced enzyme that catalyses the oxidation of heme to biliverdin. The primary deficiency of this enzyme has been shown in HO-1 knockout mice, and is characterized by intrauterine death and chronic inflammation. The first case of human HO-1 deficiency was reported in 1999. Human HO-1 deficiency has been observed to involve the endothelial cells more severely, resulting in hemolysis and disseminated intravascular coagulation. We report another case of human HO-1 deficiency in a young girl with congenital asplenia, who presented with severe hemolysis, inflammation, nephritis, which was refractory to therapy with corticosteroids, cyclophosphamide, and rituximab.