Dear Editor,
We read with interest the article by Robinson et al on use of Procalcitonin (PCT) in the pediatric population.[1] This article meticulously narrates the importance as well as shortcomings of the PCT in pediatric population. Being a neonatologist, I read the neonatal part very carefully and found few points which are either contrary or extension to the above article.
1. Authors stated that the number of patient used to generate nomogram for neonatal PCT were too low, to validate it and quotes an old study with 83 healthy subjects (1998) by Chiesa et al. However, the same group published another study in 2011 (not cited by authors) with 421 healthy participants, which provides largest normative data on PCT.[2] The nomograms are robust for term neonates but for preterms < 33 weeks the data is very small and needs further studies.
2. Author stated that PCT is better marker for early-onset sepsis (EOS) than late sepsis, which is not true. This statement is based on extrapolation of an old meta-analysis by Yu et al[3] which included 22 studies. In this meta-analysis also they found that PCT has moderate diagnostic accuracy in early as well as late-onset sepsis. So, the basis of author’s statement that PCT is better marker for early-onset sepsis is not very clear. On the contrary, Vouloumanou et al[4] published a systematic review and meta-analysis of 29 studies and concluded that the diagnostic accuracy is higher for late-onset neonatal se...
Dear Editor,
We read with interest the article by Robinson et al on use of Procalcitonin (PCT) in the pediatric population.[1] This article meticulously narrates the importance as well as shortcomings of the PCT in pediatric population. Being a neonatologist, I read the neonatal part very carefully and found few points which are either contrary or extension to the above article.
1. Authors stated that the number of patient used to generate nomogram for neonatal PCT were too low, to validate it and quotes an old study with 83 healthy subjects (1998) by Chiesa et al. However, the same group published another study in 2011 (not cited by authors) with 421 healthy participants, which provides largest normative data on PCT.[2] The nomograms are robust for term neonates but for preterms < 33 weeks the data is very small and needs further studies.
2. Author stated that PCT is better marker for early-onset sepsis (EOS) than late sepsis, which is not true. This statement is based on extrapolation of an old meta-analysis by Yu et al[3] which included 22 studies. In this meta-analysis also they found that PCT has moderate diagnostic accuracy in early as well as late-onset sepsis. So, the basis of author’s statement that PCT is better marker for early-onset sepsis is not very clear. On the contrary, Vouloumanou et al[4] published a systematic review and meta-analysis of 29 studies and concluded that the diagnostic accuracy is higher for late-onset neonatal sepsis than early-onset sepsis (AUC 0.95 vs 0.78 respectively). So, in the present article, the role of PCT in late-onset sepsis didn’t get due importance.
3. Also, this is important to emphasize that we must follow the age and gestation based nomograms for interpretation of PCT values as variation may be as high as 1000 times. Similarly, for C reactive protein also there are age and gestation based nomograms which should be used rather than using a single cutoff value across all gestation and ages.
4. The results of Neonatal Procalcitonin Intervention Study (NeoPInS) are encouraging for use of PCT in EOS. But at the same time we must keep in mind that these results cannot be extrapolated to preterm neonates and developing countries where the incidence of proven early-onset sepsis is high.
5. Author stated that PCT should not be used as a ‘rule-out’ test for sepsis in febrile infants. But, being a screening test its role will be only in “ruling out” rather than “ruling in” sepsis. Although the negative likelihood ratio of PCT alone is not very impressive, so it should be used in conjunction with other inflammatory markers to rule out sepsis.
In the era of emerging multidrug-resistant organisms, it is need of the hour to optimally use the pro-inflammatory markers for guiding the duration of the therapy and PCT seems promising one. There is urgent need of further studies to test whether PCT can be used as a decision-making tool for initiation of the therapy.
References
1 Robinson P, De SK. How to use… Procalcitonin. Arch Dis Child - Educ Pract Ed 2018;:edpract-2017- 313699. doi:10.1136/archdischild-2017-313699
2 Chiesa C, Natale F, Pascone R, et al. C reactive protein and procalcitonin: reference intervals for preterm and term newborns during the early neonatal period. Clin Chim Acta Int J Clin Chem 2011;412:1053–9. doi:10.1016/j.cca.2011.02.020
3 Yu Z, Liu J, Sun Q, et al. The accuracy of the procalcitonin test for the diagnosis of neonatal sepsis: A meta-analysis. Scand J Infect Dis 2010;42:723–33. doi:10.3109/00365548.2010.489906
4 Vouloumanou EK, Plessa E, Karageorgopoulos DE, et al. Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis. Intensive Care Med 2011;37:747–62. doi:10.1007/s00134-011-2174-8
This is a very helpful article describing the approach to children presenting with psychosis in the ED. I welcome the emphasis placed on environmental measures taken to manage agitation, which is especially important for children with Learning Disability and/or neurodevelopmental disorders. Children and young people should always be offered the option of oral medication in the first instance. We have found Promethazine or Lorazepam to be useful if medication is required in the under 12 year olds. For those aged over 12 years they may also be helpful and if necessary could be augmented by Olanzapine, Quetiapine or Risperidone, rather than using Haloperidol in this age group due to its side-effect profile.
I was fascinated by the recent article by Catherine Mark et al.
The clinical approach suggested seems reasonable, however, this will miss a lot more clinical conditions that are/may be associated with hemihypertrophy.1 The list produced in figure 2 is too restrictive.
The presence of cutaneous malformations and macrocephaly should be sought clinically. These may point towards PIK3CA-Related Segmental Overgrowth.2 3 The UK Genetic Testing Network do offer a gene panel for diagnosis. On occasions because of mosaicism, tissue biopsy may be necessary to clinch the diagnosis.
New targeted treatment options include the use of mTOR inhibitors like Sirolimus or Everolimus.4
There are two types of pathologic calcification. They are metastatic and dystrophic. Dystrophic calcification is deposition of calcium phosphate in necrotic tissue. Calcium deposition is unrelated to serum calcium and phosphate levels, which are normal . Examples include periventricular calcification in congenital cytomegalovirus infection, calcified atherosclerotic plaques, etc. Metastatic calcification is deposition of calcium phosphate in the interstitium of normal tissues. This is due to increased serum levels of calcium and/or phosphate. Examples include primary hyperparathyrodisim (due to hypercalcemia) and chronic renal failure and primary hypoparathyroidism (due to hyperphosphatemia).
In this epilogue, the subcutaneous calcifications are due to metastatic calcification rather than dystrophic calcification as there is no necrosis but serum calcium and phosphate levels are deranged.
We read with interest the clinical practice guideline by Tieder, et al. (1), proposing the new concept of Brief Resolved Unexplained Events (BRUE) replacing the old concept of apparent life-threatening events (ALTE) and the comments by Tate, et al (2). We agree that the majority of the causes of ALTE are proven not really life-threatening after the evaluation. However, we think that application of the concept of lower risk infants of BRUE and its practical recommendation might be cautious.
We have reported the analysis of 112 cases of ALTE at our institution and eighteen of them had recurrent episodes (3). We also analyzed these 112 cases of ALTE how many of them belong to the lower risk infant group of BRUE. We identified eighteen cases to belong to the lower risk group (unpublished data). Among this group, four of them had ALTE recurrence.
The BRUE guideline recommends that no necessary laboratory work to be avoided in the lower risk infants and it also recommends not to admit these infants to hospital for observation purpose. However, based on our experience, the majority of ALTE infants belong to the higher risk group and 22% (4/18) of lower risk infants presented the recurrent episodes after the first ALTE episode. Therefore, we suggest that the guideline should be examined who are really the lower risk infants and how to manage these lower risk infants, in prospective studies.
We read with interest the clinical practice guideline by Tieder, et al. (1), proposing the new concept of Brief Resolved Unexplained Events (BRUE) replacing the old concept of apparent life-threatening events (ALTE) and the comments by Tate, et al (2). We agree that the majority of the causes of ALTE are proven not really life-threatening after the evaluation. However, we think that application of the concept of lower risk infants of BRUE and its practical recommendation might be cautious.
We have reported the analysis of 112 cases of ALTE at our institution and eighteen of them had recurrent episodes (3). We also analyzed these 112 cases of ALTE how many of them belong to the lower risk infant group of BRUE. We identified eighteen cases to belong to the lower risk group (unpublished data). Among this group, four of them had ALTE recurrence.
The BRUE guideline recommends that no necessary laboratory work to be avoided in the lower risk infants and it also recommends not to admit these infants to hospital for observation purpose. However, based on our experience, the majority of ALTE infants belong to the higher risk group and 22% (4/18) of lower risk infants presented the recurrent episodes after the first ALTE episode. Therefore, we suggest that the guideline should be examined who are really the lower risk infants and how to manage these lower risk infants, in prospective studies.
Satoshi Nakagawa, Riyo Ueda, and Osamu Nomura
1. Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief Resolved Unexplained Events (Formerly Apparent Life- Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics. 2016;137(5):e20160590.
2. Tate C, Sunley R. Brief REsolved unexplained evsents (formerly apparent life-threatening events) and evaluation of lower risk infants. Arch Did Child Educ Pract Ed published online September 18, 2017.
3. Ueda R, Nomura O, Maekawa T, et al. Independent risk factors for recurrence of apparent life-threatening events in infants. Eur J Pedaitr 2017;176:443-448.
I would like to thank the authors for making this important point and highlighting the error in Illuminations (ADC E&P, 102(5), pp. 265-266.); ‘A source of tension’. A check for appropriate placement of support lines and tubes is just as important as identifying pathology when reviewing imaging. In small infants variations in head position may significantly alter the endotracheal tube (ETT) tip position and the difference between one vertebral body level and the next may be as little as 5-10mm. Therefore careful examination of the chest radiograph followed by any necessary alteration of the ETT will reduce the likelihood of complications secondary to misplacement.
It is also important to carefully check your manuscript when submitting material for publication. My intention was to point out the suboptimal positions of both the ETT and nasogastric (NG) tubes, in addition to the large tension pneumothorax. The ETT tip is too low in the distal trachea, and the NG tube tip is in the lower oesophagus and should be advanced into the stomach. Unfortunately, somewhere in the process of author checking and internal review this was omitted in error. Thanks once again for pointing this out.
I would like to thank the authors for making this important point and highlighting the error in Illuminations (ADC E&P, 102(5), pp. 265-266.); ‘A source of tension’. A check for appropriate placement of support lines and tubes is just as important as identifying pathology when reviewing imaging. In small infants variations in head position may significantly alter the endotracheal tube (ETT) tip position and the difference between one vertebral body level and the next may be as little as 5-10mm. Therefore careful examination of the chest radiograph followed by any necessary alteration of the ETT will reduce the likelihood of complications secondary to misplacement.
It is also important to carefully check your manuscript when submitting material for publication. My intention was to point out the suboptimal positions of both the ETT and nasogastric (NG) tubes, in addition to the large tension pneumothorax. The ETT tip is too low in the distal trachea, and the NG tube tip is in the lower oesophagus and should be advanced into the stomach. Unfortunately, somewhere in the process of author checking and internal review this was omitted in error. Thanks once again for pointing this out.
I read with interest the review by Green and Lillie[1] of the NICE guideline (N29) on intravenous fluid therapy in children[2]. The new guideline correctly questions the routine use of the Holliday-Segar formula for calculation of maintenance fluids[3], but the recommendation of 0.9% saline as the maintenance fluid must still be questioned.
The review opens with two contradictory statements in the first two paragraphs:
“The prescription of intravenous fluids requires an understanding of fluid homeostasis and should be tailored to the individual, the disease and the intended therapeutic goal.”
and, in reference to the NICE guideline:
“…its aim was to offer a ‘standardised approach to assessing patient’s fluid and electrolyte status and prescribing IV fluid therapy in term neonates, children and young people’.”
I agree wholeheartedly with the first statement but it does not fit with the second proposal of a “standardised” approach. The problem hinges around the idea of “replacement” and “maintenance” fluids and this was reviewed in an excellent paper by Malcolm Coulthard in 2007 when he questioned the switch from 0.18% saline to 0.45% saline as the recommended maintenance fluid[4]. The arguments he used are now doubly relevant when you move to 0.9% saline.
Patients who need fluid “replacement” need an iv fluid matching extracellular fluid composition and 0.9% saline fits the bill. Patients who need iv “maintenance” fluid need some...
I read with interest the review by Green and Lillie[1] of the NICE guideline (N29) on intravenous fluid therapy in children[2]. The new guideline correctly questions the routine use of the Holliday-Segar formula for calculation of maintenance fluids[3], but the recommendation of 0.9% saline as the maintenance fluid must still be questioned.
The review opens with two contradictory statements in the first two paragraphs:
“The prescription of intravenous fluids requires an understanding of fluid homeostasis and should be tailored to the individual, the disease and the intended therapeutic goal.”
and, in reference to the NICE guideline:
“…its aim was to offer a ‘standardised approach to assessing patient’s fluid and electrolyte status and prescribing IV fluid therapy in term neonates, children and young people’.”
I agree wholeheartedly with the first statement but it does not fit with the second proposal of a “standardised” approach. The problem hinges around the idea of “replacement” and “maintenance” fluids and this was reviewed in an excellent paper by Malcolm Coulthard in 2007 when he questioned the switch from 0.18% saline to 0.45% saline as the recommended maintenance fluid[4]. The arguments he used are now doubly relevant when you move to 0.9% saline.
Patients who need fluid “replacement” need an iv fluid matching extracellular fluid composition and 0.9% saline fits the bill. Patients who need iv “maintenance” fluid need something that matches what they would normally be drinking. If we take a 10kg child for simplicity, assume a sodium requirement of 2.5 mmol/kg and a water requirement of 100 ml/kg this equates to 1000 ml of a solution containing 25 mmol of sodium. The nearest iv solution matching this recipe is 0.18% saline containing 31 mmol of sodium in the litre administered (still a bit too much!). If you use the same volume of 0.9% saline you will be giving 154 mmol of sodium i.e. 15.4 mmol/kg which should be considered excessive.
The key to fluid management is being able to tailor the fluids to the individual as advocated in the first paragraph of the review. It has correctly been recognised that children do not usually need the volume of maintenance fluid previously advocated and it was this excess volume of water that led to problems of hyponatraemia not the lack of sodium.
The syndrome of inappropriate antidiuretic hormone (SIADH) is rare and is not the reason for the development of hyponatraemia in most cases. As a medical student I was taught by Professor George Haycock at the same hospital as the authors of this review and he was an authority on this subject. He would tell us that rather than SIADH these patients would usually have “appropriate” ADH secretion. These patients would have an unrecognised fluid deficit and needed “replacement” fluid that should be isotonic and the administration of a hypotonic solutions would lead to a dilutional hyponatraemia. Once the patient is fluid replete the solution should be changed to a hypotonic one administered at an appropriate rate. A volume of 50-80% of the previous calculated routine maintenance would be reasonable. In our patients we do not use 0.9% saline as a "maintenance " fluid, instead giving 0.45% saline plus dextrose, which is still probably too much sodium. The key is regular review of the patient with daily checking of serum electrolytes. Urine electrolytes can also be useful and I am confident that very few patients will be found to be producing urine containing 150 mmol/l of sodium unless that is what they are being given as "maintenance" fluid.
I feel that the guideline has been developed in response to the practice of poor medicine and the failure to recognise the needs of individual patients. I believe that with these guidelines poor medicine is at risk of continuing.
References
1. Green J, Lillie J. Intravenous fluid therapy in children and young people in hospital N29. Arch Dis Child Educ Pract Ed 2017; 102: 327–331.
2. Intravenous fluid therapy in children and young people in hospital NICE guideline N29. nice. org. uk/ guidance/ ng29
3. Holliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics 1957; 19: 823–32.
4. Coulthard MG. Will changing maintenance intravenous fluid from 0.18% to 0.45% saline do more harm than good? Arch Dis Child 2008; 93: 335–340
Preschool recurrent wheeze affects many children in the UK and causes great strain in their families (1). The pharmacological management during the acute episodes of wheeze offers significant relief. However, the evidence around the maintenance therapy is not conclusive.
The majority of these children grow out of the condition. The current pharmacological treatment though has not been shown to change the natural course of the disease (2, 3). Therefore, it could be argued that addressing the actual concerns of their parents/carers should be the focus that makes a significant difference to their everyday lives.
Defining personalised outcomes for preschool children with recurrent wheeze requires an understanding of what really matters for these families. A major step towards an efficient treatment would then involve reaching these outcomes and a measurement tool could monitor this.
Asthma Action Plans for children with a diagnosis of asthma have been shown to reduce the rates of hospital admissions, emergency department visits and school absence rates (4). In Australia, the introduction of a personalised wheeze action plan shows the potential to reduce the treatment with corticosteroids and to improve the education of these families around acute management but this is not clear as to whether this is related to a decrease in emergency department admissions (5).
Although education and management plans are an important part of the non-pharmacological mana...
Preschool recurrent wheeze affects many children in the UK and causes great strain in their families (1). The pharmacological management during the acute episodes of wheeze offers significant relief. However, the evidence around the maintenance therapy is not conclusive.
The majority of these children grow out of the condition. The current pharmacological treatment though has not been shown to change the natural course of the disease (2, 3). Therefore, it could be argued that addressing the actual concerns of their parents/carers should be the focus that makes a significant difference to their everyday lives.
Defining personalised outcomes for preschool children with recurrent wheeze requires an understanding of what really matters for these families. A major step towards an efficient treatment would then involve reaching these outcomes and a measurement tool could monitor this.
Asthma Action Plans for children with a diagnosis of asthma have been shown to reduce the rates of hospital admissions, emergency department visits and school absence rates (4). In Australia, the introduction of a personalised wheeze action plan shows the potential to reduce the treatment with corticosteroids and to improve the education of these families around acute management but this is not clear as to whether this is related to a decrease in emergency department admissions (5).
Although education and management plans are an important part of the non-pharmacological management of these children, other aspects should also be considered. In the UK, navigation, or signposting, through healthcare services, especially for new parents, as well as the co-ordination between primary and secondary care for the management of these children, are emerging as important interventions in order to address what really matters for families. It is therefore recommended that healthcare professionals should start their consultation by asking these parents which are their main concerns and then try to address them by the end of the consultation. In the case that they realise that these parents need further navigation around the healthcare system, they should use or highlight to them the available sources of information. Appropriate interventions need to focus on coordinating primary secondary care and eliminate unnecessary confusion for these families.
Healthcare systems are becoming more and more complicated. As providers of healthcare, we should ensure that our everyday role in the bedside is filled with all those core essentials that mean the world to our patients. Recurrent wheeze can be troublesome and there is a lot to be done around the pharmacological management, but we do not need to have it all figured out to move forward. We need to listen to the patients’ needs and assure them that their dreams are stronger than their demons.
We read with interest the article by Jane Armer and Christian De Goede appearing in a recent issue of the Journal (1). We congratulate the Authors for their superb job in summarizing such a difficult field represented by the differential diagnosis of disorders of copper metabolism. However, we noticed that in their accurate recognition of the causes of reduced serum values of ceruloplasmin, the Authors missed to mention the Congenital Disorders of Glycosylation (CDGs), which are rare as single disorders but not as a group. CDGs in fact represent nowadays more than 100 distinct genetic multisystem disorders characterized by defective glycosylation of glycoconjugates.(2) We previously signaled that patients with some types of CDGs may have low ceruloplasmin values and abnormal copper metabolism. (3, 4) Presently we know that in at least 3 types of CDGs with prevalent hepatic presentation ± CNS minor signs (TMEM199-CDG, CCDC115-CDG; ATP6AP1-CDG) and 2 with prevalent neurological presentation ± minor signs of hepatic involvement (PMM2-CDG, COG2-CDG) there is a documented disturbance of copper metabolism (Table 1). The mechanisms underlying these abnormalities are unclear, and may probably depend on the biochemical nature of ceruloplasmin itself (a glycoprotein with 6 N-linked glycans) and/or involve at least partial loss of copper transporting proteins. (5) In conclusion, in addition to the group of rare conditions signaled by the Authors, we suggest that the diagnostic algor...
We read with interest the article by Jane Armer and Christian De Goede appearing in a recent issue of the Journal (1). We congratulate the Authors for their superb job in summarizing such a difficult field represented by the differential diagnosis of disorders of copper metabolism. However, we noticed that in their accurate recognition of the causes of reduced serum values of ceruloplasmin, the Authors missed to mention the Congenital Disorders of Glycosylation (CDGs), which are rare as single disorders but not as a group. CDGs in fact represent nowadays more than 100 distinct genetic multisystem disorders characterized by defective glycosylation of glycoconjugates.(2) We previously signaled that patients with some types of CDGs may have low ceruloplasmin values and abnormal copper metabolism. (3, 4) Presently we know that in at least 3 types of CDGs with prevalent hepatic presentation ± CNS minor signs (TMEM199-CDG, CCDC115-CDG; ATP6AP1-CDG) and 2 with prevalent neurological presentation ± minor signs of hepatic involvement (PMM2-CDG, COG2-CDG) there is a documented disturbance of copper metabolism (Table 1). The mechanisms underlying these abnormalities are unclear, and may probably depend on the biochemical nature of ceruloplasmin itself (a glycoprotein with 6 N-linked glycans) and/or involve at least partial loss of copper transporting proteins. (5) In conclusion, in addition to the group of rare conditions signaled by the Authors, we suggest that the diagnostic algorithm of a challenging case of Wilson Disease should include also CDGs. They represent increasingly diagnosed conditions that warrant consideration especially when assessing children with liver involvement and/or CNS signs, a scenario which is typical of both conditions.
REFERENCES: 1. Armer J, De Goede C. How to use tests for disorders of copper metabolism. Arch Dis Child Educ Pract Ed. 2017 [Epub ahead of print] 2. Jaeken J, Péanne R. What is new in CDG? J Inherit Metab Dis. 2017;40:569-6. 3. Mandato C, Brive L, Miura Y, Davis JA, Di Cosmo N, Lucariello S, Pagliardini S, Seo NS, Parenti G, Vecchione R, Freeze HH, Vajro P. Cryptogenic liver disease in four children: a novel congenital disorder of glycosylation. Pediatr Res. 2006;59:293-8. 4. Nicastro E, Ranucci G, Vajro P, Vegnente A, Iorio R. Re-evaluation of the diagnostic criteria for Wilson disease in children with mild liver disease. Hepatology. 2010;52:1948-56. 5. Liu Y, Pilankatta R, Hatori Y, Lewis D, Inesi G. Comparative features of copper ATPases ATP7A and ATP7B heterologously expressed in COS-1 cells. Biochemistry. 2010;49:10006-12.
TABLE 1. LOW CERULOPLASMIN CDGs, AND THEIR MAIN LABORATORY CHARACTERISTICS
• TMEM199-CDG (CDG-IIp) TRANSMEMBRANE PROTEIN 199: < Ceruloplasmin, > Transaminases; > LDL-C; > AP; < Antithrombin; > H-Cu; Normal U-Cu
Dear Editor,
Show MoreWe read with interest the article by Robinson et al on use of Procalcitonin (PCT) in the pediatric population.[1] This article meticulously narrates the importance as well as shortcomings of the PCT in pediatric population. Being a neonatologist, I read the neonatal part very carefully and found few points which are either contrary or extension to the above article.
1. Authors stated that the number of patient used to generate nomogram for neonatal PCT were too low, to validate it and quotes an old study with 83 healthy subjects (1998) by Chiesa et al. However, the same group published another study in 2011 (not cited by authors) with 421 healthy participants, which provides largest normative data on PCT.[2] The nomograms are robust for term neonates but for preterms < 33 weeks the data is very small and needs further studies.
2. Author stated that PCT is better marker for early-onset sepsis (EOS) than late sepsis, which is not true. This statement is based on extrapolation of an old meta-analysis by Yu et al[3] which included 22 studies. In this meta-analysis also they found that PCT has moderate diagnostic accuracy in early as well as late-onset sepsis. So, the basis of author’s statement that PCT is better marker for early-onset sepsis is not very clear. On the contrary, Vouloumanou et al[4] published a systematic review and meta-analysis of 29 studies and concluded that the diagnostic accuracy is higher for late-onset neonatal se...
This is a very helpful article describing the approach to children presenting with psychosis in the ED. I welcome the emphasis placed on environmental measures taken to manage agitation, which is especially important for children with Learning Disability and/or neurodevelopmental disorders. Children and young people should always be offered the option of oral medication in the first instance. We have found Promethazine or Lorazepam to be useful if medication is required in the under 12 year olds. For those aged over 12 years they may also be helpful and if necessary could be augmented by Olanzapine, Quetiapine or Risperidone, rather than using Haloperidol in this age group due to its side-effect profile.
I was fascinated by the recent article by Catherine Mark et al.
The clinical approach suggested seems reasonable, however, this will miss a lot more clinical conditions that are/may be associated with hemihypertrophy.1 The list produced in figure 2 is too restrictive.
The presence of cutaneous malformations and macrocephaly should be sought clinically. These may point towards PIK3CA-Related Segmental Overgrowth.2 3 The UK Genetic Testing Network do offer a gene panel for diagnosis. On occasions because of mosaicism, tissue biopsy may be necessary to clinch the diagnosis.
New targeted treatment options include the use of mTOR inhibitors like Sirolimus or Everolimus.4
References
1. http://www.overgrowthstudy.medschl.cam.ac.uk/for-health-care-professionals/
2. https://decipher.sanger.ac.uk/gene-disorder/NBK153722#overview
3. https://www.ncbi.nlm.nih.gov/books/NBK153722/
4. https://clinicaltrials.gov/ct2/show/NCT02428296
There are two types of pathologic calcification. They are metastatic and dystrophic. Dystrophic calcification is deposition of calcium phosphate in necrotic tissue. Calcium deposition is unrelated to serum calcium and phosphate levels, which are normal . Examples include periventricular calcification in congenital cytomegalovirus infection, calcified atherosclerotic plaques, etc. Metastatic calcification is deposition of calcium phosphate in the interstitium of normal tissues. This is due to increased serum levels of calcium and/or phosphate. Examples include primary hyperparathyrodisim (due to hypercalcemia) and chronic renal failure and primary hypoparathyroidism (due to hyperphosphatemia).
In this epilogue, the subcutaneous calcifications are due to metastatic calcification rather than dystrophic calcification as there is no necrosis but serum calcium and phosphate levels are deranged.
We read with interest the clinical practice guideline by Tieder, et al. (1), proposing the new concept of Brief Resolved Unexplained Events (BRUE) replacing the old concept of apparent life-threatening events (ALTE) and the comments by Tate, et al (2). We agree that the majority of the causes of ALTE are proven not really life-threatening after the evaluation. However, we think that application of the concept of lower risk infants of BRUE and its practical recommendation might be cautious.
We have reported the analysis of 112 cases of ALTE at our institution and eighteen of them had recurrent episodes (3). We also analyzed these 112 cases of ALTE how many of them belong to the lower risk infant group of BRUE. We identified eighteen cases to belong to the lower risk group (unpublished data). Among this group, four of them had ALTE recurrence.
The BRUE guideline recommends that no necessary laboratory work to be avoided in the lower risk infants and it also recommends not to admit these infants to hospital for observation purpose. However, based on our experience, the majority of ALTE infants belong to the higher risk group and 22% (4/18) of lower risk infants presented the recurrent episodes after the first ALTE episode. Therefore, we suggest that the guideline should be examined who are really the lower risk infants and how to manage these lower risk infants, in prospective studies.
Satoshi Nakagawa, Riyo Ueda, and Osamu Nomura
1. Tieder JS,...
Show MoreI would like to thank the authors for making this important point and highlighting the error in Illuminations (ADC E&P, 102(5), pp. 265-266.); ‘A source of tension’. A check for appropriate placement of support lines and tubes is just as important as identifying pathology when reviewing imaging. In small infants variations in head position may significantly alter the endotracheal tube (ETT) tip position and the difference between one vertebral body level and the next may be as little as 5-10mm. Therefore careful examination of the chest radiograph followed by any necessary alteration of the ETT will reduce the likelihood of complications secondary to misplacement.
It is also important to carefully check your manuscript when submitting material for publication. My intention was to point out the suboptimal positions of both the ETT and nasogastric (NG) tubes, in addition to the large tension pneumothorax. The ETT tip is too low in the distal trachea, and the NG tube tip is in the lower oesophagus and should be advanced into the stomach. Unfortunately, somewhere in the process of author checking and internal review this was omitted in error. Thanks once again for pointing this out.
I would like to thank the authors for making this important point and highlighting the error in Illuminations (ADC E&P, 102(5), pp. 265-266.); ‘A source of tension’. A check for appropriate placement of support lines and tubes is just as important as identifying pathology when reviewing imaging. In small infants variations in head position may significantly alter the endotracheal tube (ETT) tip position and the difference between one vertebral body level and the next may be as little as 5-10mm. Therefore careful examination of the chest radiograph followed by any necessary alteration of the ETT will reduce the likelihood of complications secondary to misplacement.
It is also important to carefully check your manuscript when submitting material for publication. My intention was to point out the suboptimal positions of both the ETT and nasogastric (NG) tubes, in addition to the large tension pneumothorax. The ETT tip is too low in the distal trachea, and the NG tube tip is in the lower oesophagus and should be advanced into the stomach. Unfortunately, somewhere in the process of author checking and internal review this was omitted in error. Thanks once again for pointing this out.
I read with interest the review by Green and Lillie[1] of the NICE guideline (N29) on intravenous fluid therapy in children[2]. The new guideline correctly questions the routine use of the Holliday-Segar formula for calculation of maintenance fluids[3], but the recommendation of 0.9% saline as the maintenance fluid must still be questioned.
The review opens with two contradictory statements in the first two paragraphs:
“The prescription of intravenous fluids requires an understanding of fluid homeostasis and should be tailored to the individual, the disease and the intended therapeutic goal.”
and, in reference to the NICE guideline:
“…its aim was to offer a ‘standardised approach to assessing patient’s fluid and electrolyte status and prescribing IV fluid therapy in term neonates, children and young people’.”
I agree wholeheartedly with the first statement but it does not fit with the second proposal of a “standardised” approach. The problem hinges around the idea of “replacement” and “maintenance” fluids and this was reviewed in an excellent paper by Malcolm Coulthard in 2007 when he questioned the switch from 0.18% saline to 0.45% saline as the recommended maintenance fluid[4]. The arguments he used are now doubly relevant when you move to 0.9% saline.
Patients who need fluid “replacement” need an iv fluid matching extracellular fluid composition and 0.9% saline fits the bill. Patients who need iv “maintenance” fluid need some...
Show MorePreschool recurrent wheeze affects many children in the UK and causes great strain in their families (1). The pharmacological management during the acute episodes of wheeze offers significant relief. However, the evidence around the maintenance therapy is not conclusive.
Show MoreThe majority of these children grow out of the condition. The current pharmacological treatment though has not been shown to change the natural course of the disease (2, 3). Therefore, it could be argued that addressing the actual concerns of their parents/carers should be the focus that makes a significant difference to their everyday lives.
Defining personalised outcomes for preschool children with recurrent wheeze requires an understanding of what really matters for these families. A major step towards an efficient treatment would then involve reaching these outcomes and a measurement tool could monitor this.
Asthma Action Plans for children with a diagnosis of asthma have been shown to reduce the rates of hospital admissions, emergency department visits and school absence rates (4). In Australia, the introduction of a personalised wheeze action plan shows the potential to reduce the treatment with corticosteroids and to improve the education of these families around acute management but this is not clear as to whether this is related to a decrease in emergency department admissions (5).
Although education and management plans are an important part of the non-pharmacological mana...
We read with interest the article by Jane Armer and Christian De Goede appearing in a recent issue of the Journal (1). We congratulate the Authors for their superb job in summarizing such a difficult field represented by the differential diagnosis of disorders of copper metabolism. However, we noticed that in their accurate recognition of the causes of reduced serum values of ceruloplasmin, the Authors missed to mention the Congenital Disorders of Glycosylation (CDGs), which are rare as single disorders but not as a group. CDGs in fact represent nowadays more than 100 distinct genetic multisystem disorders characterized by defective glycosylation of glycoconjugates.(2) We previously signaled that patients with some types of CDGs may have low ceruloplasmin values and abnormal copper metabolism. (3, 4) Presently we know that in at least 3 types of CDGs with prevalent hepatic presentation ± CNS minor signs (TMEM199-CDG, CCDC115-CDG; ATP6AP1-CDG) and 2 with prevalent neurological presentation ± minor signs of hepatic involvement (PMM2-CDG, COG2-CDG) there is a documented disturbance of copper metabolism (Table 1). The mechanisms underlying these abnormalities are unclear, and may probably depend on the biochemical nature of ceruloplasmin itself (a glycoprotein with 6 N-linked glycans) and/or involve at least partial loss of copper transporting proteins. (5) In conclusion, in addition to the group of rare conditions signaled by the Authors, we suggest that the diagnostic algor...
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