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The hyperinflammatory immune response in severe COVID-19 infection shares features with secondary hemophagocytic lymphohistiocytosis (sHLH) in the form of fever, cytopenia, elevated inflammatory markers, and high mortality. There are contrasting opinions regarding utility of HLH 2004 or HScore in the diagnosis of severe COVID-19-related hyperinflammatory syndrome (COVID-HIS). This was a retrospective study of 47 patients of severe COVID-19 infection, suspected to have COVID-HIS and 22 patients of sHLH to other illnesses, to evaluate the diagnostic utility and limitations of HLH 2004 and/or HScore in context to COVID-HIS and to also evaluate the utility of Temple criteria for predicting severity and outcome in COVID-HIS. Clinical findings, hematological, and biochemical parameters along with the predictor of mortality were compared between two groups. Only 6.4% (3/47) of cases fulfilled ≥5/8 HLH 2004 criteria and only 40.52% (19/47) of patients showed HScore >169 in COVID-HIS group. 65.9% (31/47) satisfied the Temple criteria in COVID-HIS as compared with 40.9% (9/22) in the non-COVID group (p = 0.04). Serum ferritin (p = 0.02), lactate dehydrogenase (p = 0.02), direct bilirubin (p = 0.02), and C-reactive protein (p = 0.03) were associated with mortality in COVID-HIS. Both HScore and HLH-2004 criteria perform poorly for identifying COVID-HIS. Presence of bone marrow hemophagocytosis may help to identify about one-third of COVID-HIS missed by the Temple Criteria.

The aim of the study was to trace and understand the origin of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through various available literatures and accessible databases. Although the world enters the third year of the coronavirus disease 2019 pandemic, health and socioeconomic impacts continue to mount, the origin and mechanisms of spill-over of the SARS-CoV-2 into humans remain elusive. Therefore, a systematic review of the literature was performed that showcased the integrated information obtained through manual searches, digital databases (PubMed, CINAHL, and MEDLINE) searches, and searches from legitimate publications (1966-2022), followed by meta-analysis. Our systematic analysis data proposed three postulated hypotheses concerning the origin of the SARS-CoV-2, which include zoonotic origin (Z), laboratory origin (L), and obscure origin (O). Despite the fact that the zoonotic origin for SARS-CoV-2 has not been conclusively identified to date, our data suggest a zoonotic origin, in contrast to some alternative concepts, including the probability of a laboratory incident or leak. Our data exhibit that zoonotic origin (Z) has higher evidence-based support as compared to laboratory origin (L). Importantly, based on all the studies included, we generated the forest plot with 95% confidence intervals (CIs) of the risk ratio estimates. Our meta-analysis further supports the zoonotic origin of SARS/SARS-CoV-2 in the included studies.

An epidemic of mucormycosis followed the second wave of COVID 19 in the state of Uttar Pradesh, India in May 2021. This epidemic, however, had additional challenges to offer in the form of acute shortage of all forms of amphotericin B, posaconazole and isavuconazole. It was, therefore, planned to assess the trends in minimum inhibitory concentration (MIC) of antifungal agents, viz itraconazole and terbinafine, and provide a template for personalized therapy to see whether the results could be translated clinically. This is an observational, single-center study. Samples comprising nasal swab, nasal and paranasal sinus tissue, brain tissue, brain abscess and orbital content, derived from 322 patients from northern India with mucormycosis, of whom 215 were male and 107 were female, were used for analysis. Cultures were identified both by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and conventional methods of identification. Antifungal susceptibility was done for amphotericin B, posaconazole, isavuconazole, itraconazole and terbinafine as per Clinical Laboratory Standard Institute M38-A2. The outcome was identification of the species of mucormycosis and susceptibility to itraconazole and terbinafine besides other primary antifungal agents. Patients or the public were not involved in the design, or conduct, or reporting or in the dissemination plans of our research. Of 322 patients, 203 were culture-positive, of whom 173 were positive by both MALDI-TOF and conventional methods of identification. Final antifungal susceptibility testing was available for 150 patients. The most common Mucorales found to cause this epidemic was Rhizopus oryzae, followed by R. microsporus. Amphotericin B, posaconazole and isavuconazole had low MIC values in 98.8% of all Mucorales identified. The MIC of itraconazole was species-dependent. 97.7% of R. oryzae had MIC ≤2 µg/mL. However, only 36.5% of R. microsporus had MIC ≤2 µg/mL. For terbinafine, 85.2% of R. microsporus had MIC ≤2 µg/mL. We conclude that identification at the species level is required as antifungal susceptibilities seem to be species-dependent. Assessment of the efficacy of itraconazole and terbinafine warrants further studies with clinical assessment and therapeutic drug monitoring as they seem to be potential candidates especially when the primary agents are not available.

Background and Objectives. SARS-CoV-2 virus has caused a global pandemic as declared by the World Health Organisation (WHO) in March 2020. In India, the first case was reported in Kerala on the 30th of January, and since then, many states are active but some are showing flattening. Following the seroprevalence testing in healthy blood donors, we can monitor the spread of the virus among healthy people, thus eventually leading to implementing strategies to reduce the spread. Thus, a need was felt to conduct a study to assess the IgG antibody status in healthcare workers differentiating those who were in COVID-19 and others in non-COVID-19 emergency duties during this pandemic. Materials and Methods. 2085 blood donors were allowed to donate blood only after fulfilling all the criteria laid down by the FDA of India with additional history of excluding COVID-19 suspects. IgG antibody testing was performed by chemiluminescence, and results were noted along with their reactive status. Their reactive status was analyzed with donor information to get an idea of the risk parameters for COVID-19. Medical healthcare workers in whom the study was carried out were 560, out of which 114 had worked in COVID-19 duties and 446 had worked in non-COVID-19 emergencies areas. COVID-19 area duties were further subdivided into triage, holding area, isolation, and COVID-19-related duties. The samples were run on architect i2000 and evaluated for their plasma immunoglobulin G. Results. Amongst the asymptomatic blood donors, 1.9% was found to be COVID-19 IgG antibody positive. It was observed that maximum COVID-19 IgG positivity (57.1%) was seen in the age group 18–29 years followed by 26.2% in the age group 30–39 years. Donors in the age group 40–49 years showed antibody positivity of 16.7%, and no antibody-positive donors were found above 50 years of age. COVID-19 IgG positivity was maximum in replacement donors (61.9%) followed by family donors (28.6%) and least involuntary donors (0.6%) Blood donors who showed high IgG positivity were mainly of labor class. Antibody IgG testing on medical healthcare workers showed 2.3% positivity. The healthcare workers who were posted in COVID-19 duties showed 4.8% positivity in the holding area (waiting area with the treatment of patients till their RT PCR report comes) and 5.7% in other COVID-19 areas related to laboratory work. Healthcare workers doing duties in COVID-19 areas showed 2.7% positivity, while those doing duties in non-COVID-19 emergency areas showed a positivity of 2.2%. Conclusion. Our study shows that the prevalence of detectable antibodies was low in the general population in India and many patients were asymptomatic as seen in the blood donors, especially the labor class. Maximum exposure was present in young healthy males of labor class who remained asymptomatic. The healthcare workers were more exposed to COVID-19 as compared to the general population probably due to lack of precaution and awareness. Those doing non-COVID-19 duties were also exposed appreciably and needed to take all the precautions required for COVID-19 duties.

The second wave of COVID-19 in India was followed by large number of mucormycosis cases. Indiscriminate use of immunosuppressive drugs, underlying diseases such as diabetes, cancers, or autoimmune diseases was thought to be the cause. However, the mortality was not as high as that seen in non-COVID mucormycosis.To study the detailed characteristics of T-cells for evaluating the underlying differences in the T-cell immune dysfunction in post-COVID and non-COVID mucor patients.The study included histopathologically confirmed cases of mucor (13 post-COVID, 13 non-COVID) and 15 healthy individuals (HI). Expression of T-cell activation (CD44, HLADR, CD69, CD38) and exhaustion (CTLA, PD-1, LAG-3 and TIM-3) markers was evaluated by flow cytometry.All cases showed significant depletion of T-cells compared to HI. Both post-COVID and non-COVID groups showed increased activation and exhaustion as compared to HI. Non-COVID mucor group showed significant activation of CD4+ T cells for HLADR and CD38 (p = .025, p = .054) and marked T-cell exhaustion in form of expression of LAG-3 on both CD4+ T and CD8+ T cells in comparison with post-COVID patients (p = .011, p = .036). Additionally, co-expression of PD-1LAG-3 and LAG-3TIM-3 on CD8+ T cells was statistically significant in non-COVID mucor patients (p = .016, p = .027).Immunosuppression in non-COVID mucor showed pronounced exhaustion of T-cells in comparison to post-COVID mucor cases implicating T-cell immune dysfunction is much more severe in non-COVID mucor which are in a state of continuous activation followed by extreme exhaustion leading to poorer outcome.

An ongoing pandemic Coronavirus disease (COVID-19), caused by a newly emerged Coronavirus, SARS-CoV-2 has affected millions of people globally. One of the most crucial structural proteins of SARS-CoV-2 is the Spike glycoprotein (S-glycoprotein), for which the first de novo modelling was envisaged by our group in early 2020, and was superimposed to its predecessor SARS-CoV S-glycoprotein, to determine structural divergence, glycosylation and antigenic variation between SARS-CoV-2 and SARS-CoV. S-glycoprotein is involved in binding with the cellular receptor, membrane fusion, internalization via angiotensin-converting enzyme 2 (ACE2) receptor, and tissue tropism. Upon internalization into the target host cells, the viral genome encodes two precursor polypeptides which get processed into 16 mature nonstructural proteins that play a crucial role in replication and transcription of SARS-CoV-2. Currently S-glycoprotein is one of the most vital targets for vaccine and therapeutics development for COVID-19.

The increase in the number of antibiotic-resistant microbial strains makes it evident to discover and develop newer efficacious anti-infective drugs. High-throughput screening (HTS) is a robust technology that plays a crucial role in identifying novel anti-infective lead compounds. This chapter briefly explains the role of virtual HTS (vHTS) and HTS technologies in lead identification using various categories of chemical libraries through structure-based drug design, ligand-based drug design, in vitro cell-based assay, and biochemical assay approaches involved in the process of drug design and discovery. The chapter also gives an insightful survey of the technologies such as fluorescence, luminescence, and atomic absorbance used for the detection of biological responses in the HTS bioassays. Applications of HTS, reverse pharmacology, current challenges, and future perspectives of HTS in the pharmaceutical and biotechnology industry are discussed in the context of anti-infective drug design, discovery, and development.

The pharmaceutical industry has undergone a severe economic crunch in antibiotic discovery research due to evolving bacterial resistance along with enormous time and money that gets consumed in de novo drug design and discovery strategies. Nevertheless, drug repurposing has evolved as an economically safer and excellent alternative strategy to identify approved drugs for new therapeutic indications. Virtual high throughput screening (vHTS) and phenotype-based high throughput screening (HTS) of approved molecules play a crucial role in identifying, developing, and repurposing old drug molecules into anti-infective agents either alone or in synergistic combination with antibiotic therapy. This chapter briefly explains the process of drug repurposing/repositioning in comparison to de novo methods utilizing vHTS and HTS technologies along with ‘omics- and poly-pharmacology-based drug repurposing strategies in the identification and development of anti-microbial agents. This chapter also gives an insightful survey of the intellectual property landscape on drug repurposing. Further, the challenges and applications of drug repurposing strategies in the discovery of anti-infective drugs are exemplified. The future perspectives of drug repurposing in the context of anti-infective agents are also discussed.

Therapeutic approaches to COVID-19 treatment require appropriate inhibitors to target crucial proteins of SARS-CoV-2 replication machinery. It's been approximately 12 months since the pandemic started, yet no known specific drugs are available. However, research progresses with time in terms of high throughput virtual screening (HTVS) and rational design of repurposed, novel synthetic and natural products discovery by understanding the viral life cycle, immuno-pathological and clinical outcomes in patients based on host's nutritional, metabolic, and lifestyle status. Further, complementary and alternative medicine (CAM) approaches have also improved resiliency and immune responses. In this article, we summarize all the therapeutic antiviral strategies for COVID-19 drug discovery including computer aided virtual screening, repurposed drugs, immunomodulators, vaccines, plasma therapy, various adjunct therapies, and phage technology to unravel insightful mechanistic pathways of targeting SARS-CoV-2 and host's intrinsic, innate immunity at multiple checkpoints that aid in the containment of the disease.

Health care workers [HCW] are at a higher risk of infection SARS CoV2 infection due to frequent and close contact to patients with COVID-19.Serum samples from 500 HCW's were tested for SARS CoV2 IgG antibodies in October 2020. A questionnaire was used to collect demographic and clinical data. All these HCWs were tested for COVID-19, in 2nd week of September 2020, as a hospital policy.Anti SARS CoV2 antibodies were detected in 128/ 500 [25.6%] HCWs. A total of 195/ 500 [39%] enrolled cases had already tested positive for Covid-19 at least once in last six months by RT-PCR. Sixty eight percent of HCWs with previous COVID-19 positivity by RT- PCR tested positive for Anti SARS CoV2 antibodies, whereas only 2.76% of asymptomatic HCWs tested positive. Of 121 anti SARS-CoV-2 IgG positive persons, 70 [57.85%] had CT value ​ ​25. Low CT value and asymptomatic cases had a strong reverse statistically significant association with SARS CoV2 IgG antibody positivity.We report that sero-conversion rate in HCWs is similar to that in general population suggesting that preventive practices used in hospitals are satisfactory. Cases with low viral counts in respiratory sample and asymptomatic cases have lower rate of seroconversion.

Background Congenital pyloric atresia (CPA) is a rare anomaly with an incidence of 1 in 100,000 live births. Depending on the type of anomaly patients can either present in the neonatal period or later in life with subtle nonspecific signs and symptoms. We present our institute's experience in handling these cases over the last decade and highlight lessons learnt. Materials and methods We retrospectively reviewed records of patients diagnosed with CPA and managed at our centre between Jan 2006 to June 2016. We looked into the period of gestation, birth weight, gender, age at onset of symptoms, age at presentation to the hospital, symptoms, investigations, associated anomalies, management and outcomes and follow up periods. Results Nine patients were operated during the ten year period of study (6 males and 3 females). The median age at onset of symptoms was 06 months (01 day-36 months) and the median age of reporting to the hospital was 07 months (01 day-44 months) with a mean delay of 5 months between onset of symptoms and reporting to hospital. Six patients (67%) had associated anomalies including one with posterior urethral valve which has been reported for the first time in literature. Four out of five (80%) late presenters underwent an upper gastrointestinal endoscopy for diagnostic confirmation. All patients were operated upon and Type 1 CPA was seen in five patients (56%), Type 2 in two patients (33%) and Type 3 in one patient (11%). The overall survival was 89% as one patient with associated Epidermolysis Bullosa expired after 4 months due to fulminant sepsis. Three patients were lost to follow up and amongst the remaining five; the median follow up period is 36 months. Conclusion CPA is a rare entity that may present late with subtle signs like failure to thrive and nonbilious vomit. A high index of suspicion is mandated in these cases and an Upper Gastrointestinal Endoscopy will help in early diagnosis and avoid further unnecessary investigations. A feeding jejunostomy may benefit malnourished sick children before definitive surgery. Level of evidence Level 3, Type of study: Retrospective study.

Medulloblastoma is the most common malignant pediatric brain tumor with a high mortality rate. A comprehensive protein-coding and regulatory transcriptomics is needed to understand four major molecular subgroups. Molecularly sub-classified 22 histo-pathologically characterized Medulloblastoma (MB) into group4-MB (G4), group3-MB (G3), Wnt-MB and SHH-MB two approved methods were used Molecular Inversion Probe based Array (Oncoscan Array) and transcript-probe-based Nanostring assay. For 2-control, normal tissue extracted while reaching tumor was utilized. Out of 22, 12 samples (10 MB and 2 controls) including all sub-groups of MB was considered for long and short read sequencing. Assembly was done through PacBio and ToFU pipeline to obtain consensus transcripts. Sqanti was used to assess the quality of data and the pre-processing pipeline using 47 unique descriptors. All the above samples were aligned to human reference genome and differential expression level matrix was created between tumor and control samples. Using standard settings (minimum fold change 2.0 and p value correction was through Bonferroni and cut off p value was 0.05) heat map was generated between control and experimental samples. Using standard t-test each subtype was compared with control as well as subtypes were also compared among themselves. Novel-Canonical (NC) junctions were identified in Novel in catalogue {NIC (1-5%)}, Novel not in catalogue {NNC (25%)}, Antigenic and Intergenic transcripts. Novel-Non-Canonical junctions was not observed among the structurally classified transcripts. Also identified sub-group specific 6 fusion transcripts. Novel Antisense (AS) transcripts were also identified: CROCC, TOM1, STON2 and AK5 were WNT-specific; CENPX and EZR were common between SHH and G-3; while ZNF391 and ZNF 865 were specific to G-3 and COL18A1 and ZC3HAV1L to G-4. Differential Analysis among all subtypes of MB versus control was analyzed, we identified TTR, PDLIM3 and SFRP1 significantly up-regulated transcripts in SHH compared to both G-3/4. NRL was specifically increased in G-3 compared to SHH and G-4. While NNAT was up-regulated in G-4 compared to SHH and G-3. Have created a customized Nanostring based panel in which 35 differentially expressed transcripts, 30 AS and previously reported 22 transcripts. This panel can comprehensively and specifically characterize Indian MB and can also be used for future clinical trials and personalized medicine. Antisense transcripts and fusion transcripts can be used as target for developing small molecules. Citation Format: Neetu Singh, Nawazish Alam, Dinesh K. Sahu, Ratnesh K. Tripathi, Mayank Jain, Pratap Shankar, Hari Shyam, Archana Mishra, Anil Kumar, Uma S. Singh, Anil Chandra, Chhitij Srivastava, Bal K. Ojha, Devendra K. Gupta, Ravi Kant, Bipin Puri. Comprehensive coding and non coding transcript based characterization of Indian medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3050.

War strategies have been evolving with time and battlefield casualty care services have been trying to keep pace with the changing demands. Technological advances in the field of trauma care have revolutionised the way in which erstwhile 'non-salvageable' lives and limbs are managed with more favourable outcome. The quality of Pre-Hospital Trauma Care Services will largely determine the survival statistics of battle casualties. The surgeon has to acknowledge the various resource constraints imposed upon him in the course of delivery of expert trauma care in the battlefield. The philosophy of Tactical Field Care and TACEVAC has, to a great extent, standardized point-of-care services and the manner in which combat casualties are managed. This has resulted in increasing favourable clinical outcome in a demanding, resource restricted and challenging environment. Training of Military Surgeons prior to induction into theatres of combat is an operational imperative and has to be based on validated guidelines promulgated by apex institutes specialised in Combat Casualty Care. CASEVAC hurdles, resource paucity, command and tactical decisions, govern casualty care and impose serious constraints that are not present in an urban setting. This article highlights the basic tenets of battlefield care, the challenges associated with it and the way forward.

Non Syndromic Hearing Loss is an important cause for hearing loss. One in 1000 newborns have some hearing impairment. Over 400 genetic syndromes have been described. Non Syndromic Hearing Loss (NSHL) can be inherited in an Autosomal Dominant, Autosomal Recessive or a Sex Linked fashion. There are several reasons why genetic testing should be done in cases of NSHL, the main reasons being for genetic screening and for planning treatment. This review describes the genes involved in NSHL and the genetic mechanisms involved in the pathogenesis of the disease.

Background Genetic polymorphisms in the exon 15 and exon 16 of the ACTN3 gene are believed to be associated with athletic performance. Paratroopers are some of the fittest soldiers in the Indian Armed Forces. This study was taken up to assess if there was a significant difference in the genetic profile between paratroopers and non-paratroopers. Method Polymerase chain reaction (PCR) followed by restriction length fragment polymorphism (RFLP) was used to analyse the genetic polymorphisms in the exon 15 and 16 of the ACTN3 gene. Results There was a significant difference between paratroopers and non-paratroopers in the polymorphic loci at codon 15 and 16. Conclusions The study suggests that there is a significant difference in the genotype between paratroopers and non-paratroopers. It is likely that the differences in muscle fibres as a result of these genotypic changes confer a ‘survival advantage’; people with a homozygous genotype are more likely to pass the harsh probation and qualify for the Parachute Regiment.

After an anorectal malformation (ARM) is repaired, the goal is fecal continence of the patient. Toilet training is not complete in children below 4 years of age. Manometric and radiological studies need cooperation of the child, and are therefore of little value during the critical preschool years. In this present study, we used only clinical criteria to assess the child for constipation and incontinence after definitive operation. We included all patients of ARM wef 01 April 1998 to 31 March 2000. Only 2 children had crossed 4 years of age at the time of this assessment and therefore it was not possible to assess total continence postoperatively. We found that the incidence of incontinence was less in low anomalies and more in high or intermediate anomalies, while the incidence of constipation was higher in low anomalies and less in high and intermediate anomalies. 31% of all patients born with anorectal malformations and subjected to posterior sagittal anorectoplasty (PSARP) approach were totally continent, 38% suffered with soiling of faeces while 31% had problems of constipation. The higher incidence of constipation as well as incontinence in our study is because of a short follow-up and secondly, these problems are known to improve with passage of time. The purpose of this article is to highlight the problems of bowel control even after the definitive operation and still much more is required to improve the quality of life of these unfortunate children.

Eight patients with bowel incontinence underwent an open Malone Antegrade Continence Enema (MACE) procedure between May 1997 to May 2000. Indications for the procedure included high anorectal malformation in 3, bowel dysmotility in 1. spinal dysraphism in 3 and presacral teratoma in 1. Age at presentation varied between 06 to 12 years. All but one patient claimed excellent results. Complications of the procedure included stomal stenosis in 1, stomal leak in 2 and inadequate emptying of effluent in 1. Patient selection was the key to success. All patients except one, were children who were literate and had access to a western toilet Whereas, for the vast majority in the Indian rural setting, the procedure may not be beneficial but for a select group of bowel incontinence children, this procedure may bring a dawn of hope.

Craniosynostosis is defined as premature fusion of one or more cranial sutures, which may occur in isolation or in association with a syndromic constellation, resulting in cranial deformity. Functionally, craniosynostosis may be defined as the premature conversion of dynamic region of growth and resorption between two adjacent bones of the cranium into a static region of bony union. In the treatment of such cases, each case must be judged individually and a multidisciplinary approach is recommended. We present a case of microcephaly with bilateral coronal craniosynotosis treated with early wide linear craniectomy followed by relative normalization of skull and facial appearance.

Neonatal Lupus Erythematosus (NLE) is an uncommon condition manifesting with congenital complete heart block and occasionally other manifestations like hepatitis. Neonatal Lupus with severe cholestasis with positive anti SS-A/Ro and anti SS-B/La antinuclear antibodies in the mother and child is being reported.

In higher vertebrates, nature interposed the urinary bladder between the kidneys and the external environment to allow continence. The bladder functions as a storage organ that can empty to completion at an appropriate time and place. At times problems relating to the bladder are obvious as in an incontinent, dribbling child where the problem may be due to an anatomical or neurological anomaly. But at other times they may not be so obvious and children present to the paediatrician, with problems such as recurrent urinary tract infections or nocturnal enuresis with daytime symptoms. Under such circumstances it is important to consider a possible functional voiding disorder and evaluate the child. Early intervention may prevent renal damage due to retrograde effects of high pressure within the bladder. Managing these children requires an understanding of the functioning of the urinary bladder.

The technique of minimally invasive repair of pectus excavatum is a new operation that allows for repair of this deformity without any cartilage resection or sternal osteotomy. The procedure has revolutionized the management of pectus excavatum. Six cases of pectus excavatum were referred to our centre for surgical correction. However, based on Haller's CT index 2 merited surgery. Our results suggest that the minimally invasive repair of pectus excavatum is an exciting operation with minimal morbidity and excellent results. The innovative incorporation of thoracoscopic techniques and small but important modifications to the techniques will make this operation very effective and safe.

Short bowel syndrome, a devastating outcome after major intestinal resection, manifests as malabsorption and diarrhoea. Improved outcome in recent years has come about with better understanding of the disease and its sequelae. Medical therapy using H2 receptor antagonists, loperamide and growth hormone analogues has been found useful. Total parenteral nutrition has revolutionized the outcome of this crippling disorder. Diverse spectrums of surgical procedures aimed at deceleration of intestinal transit and intestinal lengthening have not found favour in clinical practice. Intestinal transplantation remains the only viable option when intestinal adaptation is inadequate and complications of total parenteral nutrition ensue.

Most children of total colonic anganglionosis (TCA) present with distal intestinal obstruction in the neonatal period. However, in some children it is relatively common to pass some stools and not be instantly recognised as having aganglionosis with distal ileal involvement presenting late in life. Appropriate surgical management of TCA, which can often be a diagnostic dilemma, is discussed. Case Report A one year old boy was admitted with complaints of chronic constipation with history of repeated diarrhoea and vomiting. Mother also gave history of delayed passage of meconium after birth. Examination revealed a poorly nourished child with height of 71 cms (ie. less than 10th percentile curve) and weighing 6 Kg (i.e. below the 3rd percentile of body weight). There was distension of abdomen and per rectal digital examination was followed by passage of copious amount of foul smelling faeces. While in the hospital the baby developed enterocolitis in the form of foul smelling loose stools, vomiting and fever. He was treated with IV fluid, broad-spectrum antibiotics and rectal washouts to which he responded well. A clinical diagnosis of the Hirschsprung's disease was entertained. Barium enema did not reveal any transitional zone or microcolon. Rectal biopsy confirmed rectal aganglionosis. Exploratory laparotomy revealed a normal caliber colon with a classical transitional zone in the terminal ileum (Fig 1). There was no organic intraluminal obstruction. Multiple seromuscular biopsies were taken from the rectum upwards to transitional zone including the removal of appendix. A full thickness rectal biopsy was also taken. The ileostomy was placed just proximal to the transitional zone. Histopathological examination revealed absence of ganglion cells in all samples excepts from ileum proximal to the transitional zone thus confirming the diagnosis of total colonic aganglionosis (Fig 2). Open in a separate window Fig. 1 Operative photograph showing total colonic aganglionosis with terminal ileal involvement. A cone shaped transitional zone is clearly visible in the terminal ileum

This brief update reviews the recent literature available on fluid resuscitation from hemorrhagic shock and considers the applicability of this evidence for use in resuscitation of combat casualties in the combat casualty care (CCC) environment. A number of changes need to be incorporated in the CCC guidelines: (1) dried plasma (DP) is added as an option when other blood components or whole blood are not available; (2) the wording is clarified to emphasize that Hetastarch is a less desirable option than whole blood, blood components, or DP and should be used only when these preferred options are not available; (3) the use of blood products in certain tactical field care settings where this option might be feasible (FSC, GH) is discussed; (4) 1:1:1 damage control resuscitation (DCR) with plasma: packed red blood cells (PRBC): platelets is preferred to 1:1 DCR with plasma: PRBC when platelets are available; and (5) the 30-min wait between increments of resuscitation fluid administered to achieve clinical improvement or target blood pressure has been eliminated. Also included is an order of precedence for resuscitation fluid options. There should be an emphasis on hypotensive resuscitation in order to minimize (1) interference with the body’s hemostatic response and (2) the risk of complications of over resuscitation. Hetastarch is retained as the preferred option over crystalloids when blood products are not available because of its smaller volume and the potential for long evacuations in the military setting.