Comorbid Conditions in a Cohort of Inpatients with SARS-CoV-2 and their Association with In-Hospital Mortality During the Early Phases of the Pandemic.

Introduction: Studies determined that age and associated comorbidities are associated with worse outcomes for COVID-19 patients. The aim of the present study is to examine previous electronic health records of SARS-CoV-2 patients to identify which chronic conditions are associated with in-hospital mortality in a nationally representative sample. Materials and Methods: The actual study is a cross-sectional analysis of SARS-CoV-2 infected patients who were treated in repurposed hospitals. The study includes a cohort of patients treated from 06-11-2020 to 15-03-2021 for COVID-19 associated pneumonia. To examine the presence of comorbidities, electronic health records were examined and analyzed. Results: A total of 1486 in-patients were treated in the specified period, out of which 1237 met the criteria for case. The median age of the sample was 65 years. The overall in-hospital mortality in the sample was 25.5%, while the median length of stay was 11 days. From whole sample, 16.0% of the patients did not have established diagnoses in their electronic records, while the most prevalent coexisting condition was arterial hypertension (62.7%), followed by diabetes mellitus (27.3%). The factors of age, male gender, and the number of diagnoses showed a statistically significant increase in odds ratio (OR) for in-hospital mortality. The presence of chronic kidney injury was associated with the highest increase of OR (by 3.37) for in-hospital mortality in our sample. Conclusion: The study reaffirms the findings that age, male gender, and the presence of comorbidities are associated with in-hospital mortality in COVID-19 treated and unvaccinated patients. Our study suggests that chronic kidney injury showed strongest association with the outcome, when adjusted for age, gender, and coexisting comorbidities.

Hypoxic Ischemic Encephalopathy (HIE) in Term and Preterm Infants.

Hypoxic-ischemic syndrome (HIS) and Hypoxic-ischemic encephalopathy (HIE) are conditions that affect term and premature babies, with different pathophysiology and different brain disorders. HIE appears in 1-6 / 1000 live births and 26/1000 live births in developing countries. 15-20% die in the early neonatal period, while surviving babies have severe neurological impairment, including cerebral palsy, epilepsy, visual and hearing impairment, cognitive impairment, intellectual, behavioural, and social disorders. The hypoxic-ischemic event occurs before, during or after birth. The reasons may be related to the mother, the way of birth, the placenta, and the newborn. The criteria for diagnosis of HIE include a combination of perinatal factors, the need for resuscitation, standard neurological examinations, neurophysiological monitoring, neuroimaging methods and biochemical markers. The most effective treatment for HIE is hypothermia in combination with pharmacological therapy. HIE and HIS are problem that still persist in developing countries due to inadequate obstetric care, neonatal resuscitation, and hypothermia. Current and emerging research for HIE examines new markers for early recognition, treatment, and appropriate neuroprotection of high-risk term and premature infants.

Neuro Developmental Consequences of Neonatal Hypoglycemia.

Neonatal hypoglycemia (HG) can cause neurologic damage, epilepsy, mental retardation, behavioral and personality disorders and death. The longest the HG lasts and the greatest the glucose nadir the consequences are more pronounced. Comorbidities are rather important in development of neurological damage. Hypoxemia and ischemia can cause permanent brain damage. Small for gestational age (SGA), large for gestational age (LGA), intrauterine growth restriction, gestational age bellow the 37th week, low Apgar score, sepsis, children whose mothers have toxemia, diabetes or chorioamnionitis are all newborns with increased HG risk. Comparing 34 patients with NH and 34 children without NH with similar GA, BW, BL, the Apgar score, we found statistically significant differences in motor and mental development using the Griffith scale. Children with neonatal HG fared significantly worse than those without neonatal HG. Therefore, CBG measurements and early recognition of neonatal HG is of significant importance in preventing motor and mental damage in children. A larger and well-balanced cohort of patients followed for a longer period is also necessary to clarify and discern in detail the importance of neonatal HG and other perinatal factors in neurodevelopmental damage.

The CRIB II (Clinical Risk Index for Babies II) Score in Prediction of Neonatal Mortality.

Predicting the outcome of neonatal critical patients remains elusive. The multiple factors of maternal state of health (infections, diabetes, gestosis), the placental situation (premature rupture of membranes) as well as multiple factors from the baby (small for gestational age, low Apgar score, low birth infections, mechanical ventilation, hypoglycaemia hyperglycamiea) render the approach to treatment of each patient individual and the outcome uncertain. Several approaches and scales are developed in order to assess the mortality risk in those rather complicated situations.We used the CRIB-II scale to assess the mortality risk in 80 patients delivered in a large tertiary level hospital with more than 4,000 deliveries yearly. The patients were stratified according to all the neonatal risk factors and comorbidities. The CRIB-II scale identified well the mortality rates, but not the outcomes. A large and well-balanced cohort of patients followed for a longer period is required to discern in detail the importance of CRIB-II scale in predicting outcomes in high-risk new-borns. This could serve as an assistance to personalized approach to severely sick children. In addition, it is a valuable method in comparing outcomes in different NICUs and outcomes in different times in the same NICU, thus rendering possible improvements in the same unit and among several NICU departments.

Hypoglycaemia in the Newborn.

AIM: Severe neonatal hypoglycaemia (HG) leads to neurologic damage, mental retardation, epilepsy, impaired cardiac performance and muscle weakness. The aim was to assess the frequency and severity of HG in a population of newborns. PATIENTS AND METHODS: We investigated 739 patients with neonatal hypoglycaemia (HG) (M:F=370:369) born at the University Clinic for Gynaecology and Obstetritics in Skopje in the period 2014-2016 and treated at the neonatal intensive care unit (NICU). 1416 babies were treated in the same period in NICU, and HG was observed in 52.18%. The birth weight was dominated by children with low birth weight: very low birth weight (VLBW)(<1500g) 253 children, (34,23%), low birth weight (1500-2500g) 402 (54.39%), appropriate for gestational age (AGA) 78(10.55%), and high birth weight (>4000g) 6 babies (0.81%). The gestational age was also dominated by children with low gestational age: gestational week (GW) 20-25 four children (0.54%), 26-30 GW 133 babies (17.99%), 31-35 GW472 (63.87%), and 36-40 GW130 neonates (17.59 %). 241 mothers (32.61%) have had an infection during pregnancy, 82 preeclampsia or eclampsia (11.09%), 20 diabetes mellitus (2.70%), 78 placental situations (placenta previa, abruption) (10.55%). In this study 47 babies (6.35%) with HG and co-morbidities died. There was a significant positive correlation between HG birth weight (p<0.01), gestational age (p<0.05), and the lowest Apgar score (p<0.01). Neonatal deaths were significantly correlated with GA (р>0,01), co-morbidities of the mothers (р>0,05) but not with the birth weight (р>0,05). In contrast, a significant positive correlation was found between convulsions and body weight (р<0.05). The lowest Apgar score was positively correlated with the gestational age (0.01), but not with the birth weight (0.05). CONCLUSION: Low birth weight, low gestational age, maternal risk factors, hypoxic-ischemic encephalopathy and neonatal infections are associated with HG and are a significant factor in overall neonatal mortality. Those results indicate that diminishing the frequency of the neonatal HG and the rates of neonatal mortality requires complex interaction of prenatal and postnatal interventions.

Neonatal Hypoglycemia: Risk Factors and Outcomes.

BACKGROUND AND AIMS: Severe neonatal hypoglycemia (HG) leads to neurologic damage, mental retardation, epilepsy, personality disorders, impaired cardiac performance and muscle weakness. We aimed to assess the clinical characteristics of children with hypoglycemia in a random population of newborns. PATIENTS, METHODS AND RESULTS: We investigated 84 patients (M:F=35:48) born at the University Clinic for Gynecology and Obstetrics in Skopje (hospitalized in the NICU) who were found to have hypoglycemia. In total 89.25% of the babies were premature. The mean birth weight was 1795.95 +/596.08 grams, the mean birth length was 41.92+/- 4.62 cm, while the mean gestational age was 33.05±3.19 weeks. 32 children (38.08%) were very low birth weight (<1500g), 38 (45.22%) were low birth weight (1500-2500g), while there were 8 children (9.52%) appropriate for age BW and no high BW for age patients (>4000 g). HG duration was 2.42+/-2.41 hours. In the group as a whole, hypoxic-ischemic encephalopathy (HIE) was found in 3 children (3.57%), infections in 22 (26.18%), respiratory distress syndrome (RDS) in 9 patients (10.62%), intracranial haemorrhage in 2 patients (2.38%). There were no inborn errors of metabolism. There were two deaths (2.38%). CONCLUSION: Neonatal HG is a significant factor in the overall neonatal mortality. HG can also cause severe invalidity. We found that infections, LBW and low gestational age were most commonly associated with neonatal HG. However the Spearman test showed weak direct correlation, without statistical significance. Neonatal HG requires complex and team interaction of prenatal and postnatal approaches to reduce the incidence of seizures, their consequences and the overall mortality. Special consideration is to be taken in measures that avoid neonatal infections, HIE, LBW and low gestational age. Further studies on a larger population are needed to fully understand and prevent the phenomenon of HG in newborns.

Craniosynostosis: Acrocephalosyndactyly (Apert Syndrome) Diagnosed in a Newborn.

We report a 10 days old newborn with brachycephaly, midfacial hypoplasia, syndactyly and broad distal phalanx of thumb and big toe. At the 20th gestational weeks an enlargement of the left cerebral ventricle and malformation of the fingers of the hands and toes were noticed on a regular ultrasound examination. The aforementioned malformations were observed at birth and at the age of 11 months. The large fontal was closed; the small one was palpable at the tip of the finger. Brachycephaly was evident with high full forehead, flat occiput, and irregular craniosynostosis especially at the coronal suture. Cutaneous syndactyly was present at both hands (fingers II-V), with almost complete fusion of the second, third and fourth fingers. Distal phalanges of the thumbs were broad as well as distal hallux. There was cutaneous syndactyly of the feet. Mental development at the age of 11 months was normal. Apert syndrome is a sporadic disorder. Rarely, inheritance is autosomal dominant. Appropriate management includes surgical treatment of the syndactylies, follow up of the eventual airway compromise and hearing difficulties. This is a report of a patient identified as a newborn.

Obesity in Childhood and Adolescence, Genetic Factors.

Obesity and excess weight are a pandemic phenomenon in the modern world. Childhood and adolescent obesity often ends up in obesity in adults. The costs of obesity and its consequences are staggering for any society, crippling for countries in development. Childhood obesity is also widespread in Macedonia. Metabolic syndrome, dyslipidemia and carbohydrate intolerance are found in significant numbers. Parents and grandparents are often obese. Some of the children are either dysmorphic, or slightly retarded. We have already described patients with Prader-Willi syndrome, Bardet-Biedl syndrome or WAGR syndrome. A genetic screening for mutations in monogenic obesity in children with early, rapid-onset or severe obesity, severe hyperphagia, hypogonadism, intestinal dysfunction, hypopigmentation of hair and skin, postprandial hypoglycaemia, diabetes insipidus, abnormal leptin level and coexistence of lean and obese siblings in the family discovers many genetic forms of obesity. There are about 30 monogenic forms of obesity. In addition, obesity is different in ethnic groups, and the types of monogenic obesity differ. In brief, an increasing number of genes and genetic mechanisms in children continue to be discovered. This sheds new light on the molecular mechanisms of obesity and potentially gives a target for new forms of treatment.

The Child Health Care System of Macedonia.

Macedonia is a multiethnic developing country with a new democratic political system in transition from a former communist country. The country gained independence as former Yugoslav Republic of Macedonia in 1991. Recent health reforms have privatized pediatric primary care and introduced family doctors alongside primary care pediatricians. Increasing privatization of hospitals have left the state-run hospitals short of pediatric specialists and subspecialists as doctors moved to private hospitals for better salaries and working conditions. There is little coordinated action between the Ministry of Health, health insurance fund, and Macedonian pediatricians to overcome the problems that now exist within the pediatric/child health system because of these recent reforms, which were politically driven without consultation with the Macedonian Pediatric Association. These recent decisions will have an adverse effect on the quality of care for children and families, which will likely continue for another 5-10 years.

Neonatal Hypoglycemia: A Continuing Debate in Definition and Management.

Neonatal hypoglycemia (NH) is one of the most common abnormalities encountered in the newborn. Maintaining glucose homeostasis is one of the important physiological events during fetal-to-neonatal transition. Transient low blood glucose concentrations are frequently encountered in the majority of healthy newborns and are the reflections of normal metabolic adaptation processes. Nevertheless, there is a great concern that prolonged or recurrent low blood glucose levels may result in long-term neurological and developmental consequences. Strikingly, it was demonstrated that the incidence and timing of low glucose concentrations in the groups most at risk for asymptomatic neonatal hypoglycemia, did not find association between repetitive low glucose concentrations and poor neurodevelopmental outcomes. On the contrary, NH due to hyperinsulinism is strongly associated with brain injury. Fundamental issue of great professional controversy is concerning the best manner to manage asymptomatic newborns NH. Both, overtreating NH and undertreating NH are poles with significant potential disadvantages. Therefore, NH is one of the most important issues in the day-to-day practice. This article appraises the critical questions of definition (widely accepted blood glucose concentration: < 2.6 mmol/l or 47 mg/dl), follow-up ad management of NH.

Congenital erythropoietic porphyria with two mutations of the uroporphyrinogen III synthase gene (Cys73Arg, Thr228Met).

Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase (UROS). We describe a 14-year-old girl with red urine since infancy, progressive blistering and scarring of the skin, and moderate hemolytic anemia. After years of skin damage, her face is mutilated; she has a bald patch on the scalp, hypertrichosis of the neck, areas of skin darkening, and limited joint movements of the hands. Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. Sequencing of the UROS gene identified two mutations causing CEP (Cys73Arg, Thr228Met). The patient lesions are progressing. Bone marrow transplantation and/or gene therapy are proposed as the next steps in her treatment. In brief, we describe a CEP with confirmed two pathogenic mutations, severe phenotype and discuss the various treatment options available.

Childhood craniopharyngioma in Macedonia: incidence and outcome after subtotal resection and cranial irradiation.

BACKGROUND: craniopharyngioma is a frequent tumor in children with challenging surgical, endocrine, and visual consequences. We evaluated our experience in treating craniopharyngioma and its incidence in Macedonia. METHODS: Thirteen children (9 male and 4 female) with craniopharyngioma (age 9.55 ± 3.74 years; range 2.90-15.11) who had been treated between 1989 and 2008 in Macedonia were reviewed. RESULTS: initial signs were vision disturbances (10 children), seizures (1), growth retardation (13), and diabetes insipidus (DI) (2). All children were subjected to subtotal surgical removal. Cranial irradiation was performed in 12 of the 13 children, and intracystic bleomycin was given to one child. The patients were followed up for 6-229 months (mean ± SD: 107.00 ± 74.04 months). All children had multiple pituitary deficiencies after surgical removal of the tumor. Body mass index increased from 16.93 ± 6.34 standard deviation scores (SDS) at diagnosis to 26.33 ± 5.91 SDS (P>0.005) at the last follow-up. DI was permanent in 9 of the 13 children, and multiple pituitary deficiencies were seen in all children. Treatment with growth hormone resulted in normalization of adult height from -1.27 ± 1.52 SDS at the start of the treatment to -0.13 ± 1.39 SDS at the last followup. The final height was not significantly lower than the genetic target height (P>0.005). The permanent deficit was visual impairment: blindness in one or both eyes in 4 children, bitemporal hemianopsia in 4, and other defects in 2. Recurrence of the disease was ruled out in one child after 31 months. No mortality was observed in the observation period of 104.92 ± 76.11 months. CONCLUSIONS: the overall incidence of craniopharyngioma in the period of 1989-2008 in Macedonia was 1.43 per 1 000 000 person-years. Subtotal resection and systematic irradiation showed good life quality of survivors.

An epidemiologic study of some characteristics of lung cancer.

OBJECTIVE: The principal aim of this study was to determine lung cancer distribution according to some epidemiologic and demographic variables in patients diagnosed to have this disease. METHODS: The study included 1731 patients diagnosed to have lung cancer between January 1, 1990 and December 31, 1999. Data were gathered from the patients' history of disease and from the bronchoscopy Record book. Establishment of significance in analyzed differences between some statistical series was done using Pearson's chi2 test and Kolmogoroff-Smirnoff test (K-S test) for one and two samples. RESULTS: The majority of male patients (out of a total of 1523 males) were in the age range of 60 to 64 years (21.7%). The age range of 65 to 69 was predominant in the female patients (16.3%). The distribution by sex and age showed significant differences (K-S; p < 0.05). 81.4% of the male patients and 39% of the female patients were smokers. This characteristic was significantly associated with the patients' sex (chi2 = 258.12; DF = 1; p < 0.01). Bronchoscopic localization of the pathological process was not significantly correlated with the habit of cigarette smoking (Kruskal-Wallis chi2 = 1.36; DF = 2; p > 0.05). Pathohistological diagnosis and smoking were significantly correlated (chi2 = 49.37; DF = 2; p < 0.01). CONCLUSIONS: In the study period, the men fell ill seven times as frequently as the women. The pathological process was most commonly localized in the right and left upper lobes. The predominant histologic type in men was squamous cell carcinoma (SQC), and in women--adenocarcinoma (ADC). Smokers were the greatest number in the patients with SQC and small cell carcinoma. ADC was most common in nonsmokers.