Premature declaration of death

A 3-year-old girl woke up during her funeral before being officially declared dead after doctors mistakenly presumed her dead the first time. 

The family of Camila Roxana Martinez Mendoza is accusing the Salinas de Hidalgo Basic Community Hospital of negligence after reportedly declaring the toddler dead too soon. 

The young girl was experiencing stomach pains, vomiting and fever when her mother, Mary Jane Mendoza, took her to see a pediatrician in the family’s hometown of Villa de Ramos on Aug. 17, El Universal newspaper reported. 

The doctor escalated the issue and recommended that the child be taken to the hospital in the central Mexican state of San Luis Potosí to be treated for dehydration. 

Doctors at Salinas de Hidalgo Basic Community Hospital placed a cold towel over her little body to lower her body temperature and placed a pulse oximeter on one of her fingers to keep track of her oxygen levels.

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Camila was released from the hospital with a prescription for paracetamol — which treats pain and fever — but continued to deteriorate as the day continued. She was seen by another doctor who instructed her mother to feed her fruits and water and prescribed a different medication. 

Despite the medications and advice from medical experts, the toddler continued vomiting. Her worried parents took her to see another doctor, who suggested she be rushed to the emergency room. 

Camila was readmitted to Salinas between 9 and 10 p.m., and doctors worked to help the young girl. 

“They wanted to give her (intravenous therapy). They took a long time to put oxygen on her,” her mother said. “They didn’t put it on her because they couldn’t find her little veins; finally, a nurse managed it.” 

After about 10 minutes, the IV was removed from the little girl, who was then taken away to rest. “She still was hugging me, they took her away and told me, ‘You have to let her rest in peace.'” the grieving mother remembered. 

Bizarrely, Mendoza was then kept from her ailing daughter in a separate, locked room. She was able to get out but still could not get into the room where her daughter was being kept. Camila was later declared dead from dehydration. 

The next day, a funeral viewing was held for friends and family to mourn the beloved toddler when Mendoza noticed the glass window of the coffin fogging up. 

Other funeral attendees told the distraught mother that she must be hallucinating and dissuaded her from opening the coffin. However, Camila’s paternal grandmother reportedly rushed to take a closer look when she noticed Camila’s eyes moving and shockingly discovered she had a pulse. 

Camila was rushed by ambulance back to the Salinas hospital, where doctors unsuccessfully attempted to revive her and declared her dead again — this time from cerebral edema (brain swelling). 

“That was really where my baby was done. We are devastated because my girl was a very happy person, she got along with everyone, she didn’t single anyone out,” Mendoza said. “We have many people on the ranch who support us because she was cherished.” 

The family was planning to send Camila to her first day of kindergarten this week. 

https://nypost.com/2022/08/24/girl-3-declared-dead-wakes-up-at-her-funeral-then-dies-again/

See: https://childnervoussystem.blogspot.com/2018/05/premature-organ-donation.html

https://childnervoussystem.blogspot.com/2018/04/premature-death-declaration.html

 

 

 
 

Expanding the phenotype of DNAJC30-associated Leigh syndrome

Zawadzka M, Krygier M, Pawłowicz M, Wilke MVMB, Rutkowska K, Gueguen N, Desquiret-Dumas V, Klee EW, Schimmenti LA, Sławek J, Procaccio V, Płoski R, Mazurkiewicz-Bełdzińska M. Expanding the phenotype of DNAJC30-associated Leigh syndrome. Clin Genet. 2022 Jul 21. doi: 10.1111/cge.14196. Epub ahead of print. PMID: 35861300.

Abstract

Leigh syndrome (LS) is a progressive neurodegenerative disease, characterized by extensive clinical, biochemical, and genetic heterogeneity. Recently, biallelic variants in DNAJC30 gene, encoding a protein crucial for the repair of mitochondrial complex I subunits, have been associated with Leber hereditary optic neuropathy and LS. It was suggested that clinical heterogeneity of DNAJC30-associated mitochondrial disease may be attributed to digenic inheritance. We describe three Polish patients, a 9-year-old boy, and female and male siblings, aged 17 and 11 years, with clinical and biochemical manifestations of LS. Exome sequencing (ES) identified a homozygous pathogenic variant in DNAJC30 c.152A>G, p.(Tyr51Cys) in the 9-year-old boy. In the siblings, ES identified two DNAJC30 variants: c.152A>G, p.(Tyr51Cys) and c.130_131del, p.(Ser44ValfsTer8) in a compound heterozygous state. In addition, both siblings carried a novel heterozygous c.484G>T, p.(Val162Leu) variant in NDUFS8 gene. This report provides further evidence for the association of DNAJC30 variants with LS. DNAJC30-associated LS is characterized by variable age at onset, movement disorder phenotype and normal or moderately elevated blood lactate level. Identification of a candidate heterozygous variant in NDUFS8 supports the hypothesis of digenic inheritance. Importantly, DNAJC30 pathogenic variants should be suspected in patients with LS irrespective of optic nerve involvement.

Neurodevelopmental outcomes at 1 year in infants of mothers who tested positive for SARS-CoV-2 during pregnancy

 Edlow AG, Castro VM, Shook LL, Kaimal AJ, Perlis RH. Neurodevelopmental Outcomes at 1 Year in Infants of Mothers Who Tested Positive for SARS-CoV-2 During Pregnancy. JAMA Netw Open. 2022 Jun 1;5(6):e2215787. doi: 10.1001/jamanetworkopen.2022.15787. PMID: 35679048; PMCID: PMC9185175.

Abstract

Importance: Epidemiologic studies suggest maternal immune activation during pregnancy may be associated with neurodevelopmental effects in offspring.

Objective: To evaluate whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth.

Design, setting, and participants: This retrospective cohort study examined live offspring of all mothers who delivered between March and September 2020 at any of 6 Massachusetts hospitals across 2 health systems. Statistical analysis was performed from October to December 2021.

Exposures: Maternal SARS-CoV-2 infection confirmed by a polymerase chain reaction test during pregnancy.

Main outcomes and measures: Neurodevelopmental disorders determined from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnostic codes over the first 12 months of life; sociodemographic and clinical features of mothers and offspring; all drawn from the electronic health record.

Results: The cohort included 7772 live births (7466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean (SD) maternal age of 32.9 (5.0) years; offspring were 9.9% Asian (772), 8.4% Black (656), and 69.0% White (5363); 15.1% (1134) were of Hispanic ethnicity. Preterm delivery was more likely among exposed mothers: 14.4% (32) vs 8.7% (654) (P = .003). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses in unadjusted models (odds ratio [OR], 2.17 [95% CI, 1.24-3.79]; P = .006) as well as those adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status (adjusted OR, 1.86 [95% CI, 1.03-3.36]; P = .04). Third-trimester infection was associated with effects of larger magnitude (adjusted OR, 2.34 [95% CI, 1.23-4.44]; P = .01).

Conclusions and relevance: This cohort study of SARS-CoV-2 exposure in utero found preliminary evidence that maternal SARS-CoV-2 may be associated with neurodevelopmental sequelae in some offspring. Prospective studies with longer follow-up duration will be required to exclude confounding and confirm these associations.

Decompressive craniectomy vs standard medical care at 24 months

Kolias AG, Adams H, Timofeev IS, Corteen EA, Hossain I, Czosnyka M, Timothy J, Anderson I, Bulters DO, Belli A, Eynon CA, Wadley J, Mendelow AD, Mitchell PM, Wilson MH, Critchley G, Sahuquillo J, Unterberg A, Posti JP, Servadei F, Teasdale GM, Pickard JD, Menon DK, Murray GD, Kirkpatrick PJ, Hutchinson PJ; RESCUEicp Trial Collaborators. Evaluation of Outcomes Among Patients With Traumatic Intracranial Hypertension Treated With Decompressive Craniectomy vs Standard Medical Care at 24 Months: A Secondary Analysis of the RESCUEicp Randomized Clinical Trial. JAMA Neurol. 2022 Jul 1;79(7):664-671. doi: 10.1001/jamaneurol.2022.1070. PMID: 35666526; PMCID: PMC9171657.

Abstract

Importance: Trials often assess primary outcomes of traumatic brain injury at 6 months. Longer-term data are needed to assess outcomes for patients receiving surgical vs medical treatment for traumatic intracranial hypertension.

Objective: To evaluate 24-month outcomes for patients with traumatic intracranial hypertension treated with decompressive craniectomy or standard medical care.

Design, setting, and participants: Prespecified secondary analysis of the Randomized Evaluation of Surgery With Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp) randomized clinical trial data was performed for patients with traumatic intracranial hypertension (>25 mm Hg) from 52 centers in 20 countries. Enrollment occurred between January 2004 and March 2014. Data were analyzed between 2018 and 2021. Eligibility criteria were age 10 to 65 years, traumatic brain injury (confirmed via computed tomography), intracranial pressure monitoring, and sustained and refractory elevated intracranial pressure for 1 to 12 hours despite pressure-controlling measures. Exclusion criteria were bilateral fixed and dilated pupils, bleeding diathesis, or unsurvivable injury.

Interventions: Patients were randomly assigned 1:1 to receive a decompressive craniectomy with standard care (surgical group) or to ongoing medical treatment with the option to add barbiturate infusion (medical group).

Main outcomes and measures: The primary outcome was measured with the 8-point Extended Glasgow Outcome Scale (1 indicates death and 8 denotes upper good recovery), and the 6- to 24-month outcome trajectory was examined.

Results: This study enrolled 408 patients: 206 in the surgical group and 202 in the medical group. The mean (SD) age was 32.3 (13.2) and 34.8 (13.7) years, respectively, and the study population was predominantly male (165 [81.7%] and 156 [80.0%], respectively). At 24 months, patients in the surgical group had reduced mortality (61 [33.5%] vs 94 [54.0%]; absolute difference, -20.5 [95% CI, -30.8 to -10.2]) and higher rates of vegetative state (absolute difference, 4.3 [95% CI, 0.0 to 8.6]), lower or upper moderate disability (4.7 [-0.9 to 10.3] vs 2.8 [-4.2 to 9.8]), and lower or upper severe disability (2.2 [-5.4 to 9.8] vs 6.5 [1.8 to 11.2]; χ27 = 24.20, P = .001). For every 100 individuals treated surgically, 21 additional patients survived at 24 months; 4 were in a vegetative state, 2 had lower and 7 had upper severe disability, and 5 had lower and 3 had upper moderate disability, respectively. Rates of lower and upper good recovery were similar for the surgical and medical groups (20 [11.0%] vs 19 [10.9%]), and significant differences in net improvement (≥1 grade) were observed between 6 and 24 months (55 [30.0%] vs 25 [14.0%]; χ22 = 13.27, P = .001).

Conclusions and relevance: At 24 months, patients with surgically treated posttraumatic refractory intracranial hypertension had a sustained reduction in mortality and higher rates of vegetative state, severe disability, and moderate disability. Patients in the surgical group were more likely to improve over time vs patients in the medical group.

The serotonin theory of depression

Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2022 Jul 20. doi: 10.1038/s41380-022-01661-0. Epub ahead of print. PMID: 35854107. 

Abstract 

The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT1A receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration. 

From the article: 

The chemical imbalance theory of depression is still put forward by professionals, and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue antidepressant medication and may discourage people from discontinuing treatment, potentially leading to lifelong dependence on these drugs... 

One study in this review found that antidepressant use was associated with a reduction of plasma serotonin, and it is possible that the evidence for reductions in SERT density and 5-HT1A receptors in some of the included imaging study reviews may reflect compensatory adaptations to serotonin-lowering effects of prior antidepressant use. Authors of one meta-analysis also highlighted evidence of 5-HIAA levels being reduced after long-term antidepressant treatment. These findings suggest that in the long-term antidepressants might produce compensatory changes that are opposite to their acute effects. Lowered serotonin availability has also been demonstrated in animal studies following prolonged antidepressant administration. Further research is required to clarify the effects of different drugs on neurochemical systems, including the serotonin system, especially during and after long-term use, as well as the physical and psychological consequences of such effects. 

This review suggests that the huge research effort based on the serotonin hypothesis has not produced convincing evidence of a biochemical basis to depression. This is consistent with research on many other biological markers. We suggest it is time to acknowledge that the serotonin theory of depression is not empirically substantiated.