Mathematical model of aging in COVID-19.

Background: The aim was examination of the intimamedia thickness of carotid arteries in COVID-19 infection. Methods: In 50 patients, the thickness of the intimomedial complex (IMT) in the common carotid arteries was measured. The values were compared with the control group in 2006-9. The condition of the lungs was assessed by ultrasound score (It score) (0-42) as mild (0-14) or mediumsevere (15-28) Covid. IMT thickening risk factors and the value of fibrinogen, IL-6 and CRP were recorded. Two IMT prediction models were formed. The socio-epidemiological model predicts the development of IMT based on epidemiological factors. Apart from these factors, the second model also includes the values of the mentioned biomarkers. Results: It score 20±6, IMT values right: median 0.99 mm, p25=0.89, p75=1.14; left: 1±0.22 mm. Control: IMTright: median 0.7 mm, p25=0.68 mm; p75=0-9 mm; left: median=0.75 mm, p25=0.6 mm, p75=1.0 mm. The group/control difference is highly significant. Epide mio - logical model: logit (IMT)= 4.463+(2.021+value for GEN)+(0.055x AGE value)+(-3.419x RF value)+(-4.447x SM value)+(5.115x HTA value)+(3.56x DM value)+ (22.389x LIP value)+(24.206x CVD value)+(1.449x other value)+(-0.138x It score value)+(0.19xBMI value). Epidemiological-inflammatory model: logit (IMT)=5.204+ (2.545x GEN value)+(0.076x AGE value)+(-6.132x RF value)+(-7.583x SM value)+(8.744x HTA value)+(6.838x DM value)+(25.446x LIP value)+(28.825x CVD value)+ (2.487x other value)+(-0.218xIt score value)+(0.649x BMI value) +(-0.194x fibrinogen value)+(0.894x IL-6 value)+(0.659x CRP value). Values for both models Exp(B)=4.882; P of sample=0.83; logit=-0.19; OR= 23.84; model accuracy for the first model 87% and for the second 88%; Omnibus test of the first model c2=34.324; p=0.000; reliability coefficient -2LogLH=56.854; Omnibus test of the second model c2=39.774; p=0.000; and -2LogLH=51.403. Conclusions: The ageing of blood vessels in COVID-19 can be predicted.

Sensorineural Hearing Loss in a Child with Succinic Semialdehyde Dehydrogenase Deficiency.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal-recessive disorder of gamma-aminobutyric acid (GABA) metabolism, resulting in accumulation of GABA and gamma-hydroxybutyric acid (GHB) in physiological fluids. Approximately 450 patients have been diagnosed worldwide with this inherited neurotransmitter disorder. We report on a five-year-old male patient, homozygous for the pathogenic variant (NM_170740:c.1265G>A) in ALDH5A1 presenting with an unexpected association of typical SSADH deficiency manifestations with bilateral sensorineural hearing loss (SNHL). Brainstem evoked response audiometry (BERA) testing showed mid-frequency sensorineural hearing damage that suggested a hereditary component to SNHL. Whole exome sequencing (WES) failed to discern other genetic causes of deafness. Several variants of uncertain significance (VUS) detected in genes known for their role in hearing physiology could not be verified as the cause for the SNHL. It is known that central auditory processing depends on a delicate balance between excitatory and inhibitory neurotransmission, and GABA is known to play a significant role in this process. Additionally, excessive concentrations of accumulated GABA and GBH are known to cause a down-regulation of GABA receptors, which could have an adverse influence on hearing function. However, these mechanisms are very speculative in context of SNHL in a patient with inherited disorder of GABA metabolism. Injury of the globi pallidi, one of hallmarks of SSADH deficiency, could also be a contributory factor to SNHL, as was suspected in some other inborn errors in metabolism. We hope that this case will contribute to the understanding of phenotypic complexity of SSADH deficiency.

Lymphatic drainage map of the head and neck skin squamous cell carcinoma detected by sentinel lymph node biopsy.

OBJECTIVE: Squamous cell carcinoma of the skin often affects the scalp and neck region and has a potential for complex lymphatic metastases. The aim of this study was to examine the pattern of lymphatic drainage that would enable better insight and prediction of lymphatic metastasis of head and neck squamous cell carcinoma (HNSCC) in relation to the anatomical localization of the primary process. PATIENTS AND METHODS: A prospective analysis included 64 patients who underwent sentinel lymph node (SLN) biopsy. The biopsy was performed in patients with high-risk cutaneous head and neck squamous cell carcinoma between 2006 and 2010. RESULTS: SLNs in tumors of the forehead, temporal region, lateral cheek, and auricle were found in the cervical region at level II and parotid lymph nodes (p<0.001). In tumors of the nose, periorbital region, and postauricular tumors, SLNs were found in parotid lymph nodes (p<0.001), in tumors of the medial cheek in level I cervical lymph nodes and parotid lymph nodes (p=0.003). In tumors of the neck, SLNs were detected in the cervical region at level IV, whereas in tumors of the posterior scalp they were found in the occipital region (p<0.001). CONCLUSIONS: The results of SLN biopsy in high-risk cutaneous HNSCCs show the regularity of metastasis based on which a lymphatic drainage map can be constructed and thus potential metastatic sites depending on the primary tumor localization predicted.

Clinical and genetic data on Lafora disease patients of Serbian/Montenegrin origin.

Lafora disease (LD) is an autosomal recessive, progressive disorder characterized by myoclonus and seizures, inexorable neurologic deterioration, cognitive decline and poor prognosis. LD is caused by mutations either in the EPM2A or in NHLRC1 genes. Here we report clinical and genetic findings on 14 LD patients from 10 families of Serbian/Montenegrin origin. Molecular diagnostics was performed by sequencing the coding regions of the EPM2A and NHLRC1 genes. In addition, haplotype analysis of the chromosomes carrying the two most frequent mutations (c.1048-1049delGA and deletion of the whole NHLRC1 gene) using eight different markers flanking the NHLRC1 gene was conducted. We identified one new mutation (c.1028T>C) along with the 3 previously reported mutations (c.1048-1049delGA, c.990delG, deletion of the whole NHLRC1 gene), all of which were located on the NHLRC1 gene. The two predominant mutations (c.1048-1049delGA and complete NHLRC1 gene deletion) appear to be founder mutations. In addition to documenting the genetic heterogeneity observed for LD, our study suggests that mutations in the NHLRC1 gene may be a common cause of LD in the Serbian/Montenegrin population, primarily because of a founder effect.

Imported parasitic infections in Serbia.

BACKGROUND: Travel to the tropics is associated with a risk of parasitic infection, which is increasing in parallel with the rise in travel to these areas. We thus examined the prevalence and trend in the occurrence of parasitic infections in Serbian travelers. METHODS: A retrospective analysis of the medical records of all travelers returning from tropical and subtropical areas, who presented at the Institute for Infectious and Tropical Diseases in Belgrade between January 2001 and January 2008, was performed. RESULTS: Of a total of 2440 travelers, 169 (6.9%) were diagnosed with a parasitic infection, including malaria in 79, intestinal parasites in 84 (pathogenic species in 30 and non-pathogenic in 54), filariasis in four, and visceral leishmaniasis and fascioliasis in one patient each. Importantly, of the whole series only 583 (23.9%) were symptomatic, of which 19.4% were found to be infected with a parasite. The single pathogenic parasite occurring in asymptomatic patients was Giardia intestinalis. CONCLUSIONS: Parasitic infection causing symptomatic disease among travelers returning from tropical areas to Serbia is not infrequent. In view of the expected increase in travel to the tropics, diagnostic protocols for tropical parasitic diseases should take these data into account.

Epidemiology and diagnostics of visceral leishmaniasis in Serbia.

A retrospective epidemiological and diagnostic study of visceral leishmaniasis (VL) was carried out during the period 2001-2007 and included patients suspected of VL who had been diagnosed at the Parasitological Laboratory at the Institute for Infectious and Tropical Diseases, Belgrade. Diagnosis of VL was confirmed by microscopic examination of Giemsa-stained bone marrow (BM) smears. BM smears from 134 patients were examined; 22 cases of VL were diagnosed, the majority of which involved individuals who had been on holiday at the Montenegrian sea coast. The sensitivity of the initial BM smears was inadequate; this required the application of a serological test, adapted for routine use, for the diagnosis of VL.

[Correlation between results of PCR and specific serological tests in diagnosis of Epstein-Barr virus in patients with mononucleosis syndrome].

Routine laboratory diagnosis of infectious mononucleosis is based on EBV serological testing, but due to problems in interpretation of results, molecular methods, especially PCR, are often necessary. The aim of the present study was to investigate correlation between results of PCR and specific serological tests in diagnosis of Epstein-Barr virus in patients with mononucleosis syndrome. The study comprised 68 patients with mononucleosis syndrome. Their blood samples were tested using ELISA for detection of 4 EBV specific antibodies (anti-VCA IgM and IgG, anti-EA-D IgG and anti-EBNA-1 IgG) and PCR for detection of EBV DNA. According to results of serology 42 patients had acute primary infection, 2 reactivation, 1 chronic active infection, 19 past infection, and 4 have been EBV seronegative. EBV DNA was detected in 17 patients (25%) and all of them were serologically defined as acutely infected. PCR was useful for resolving unclear serology results. Specific serology is the first step in diagnosis of IM, but PCR may serve as a useful additional diagnostic tool for clarifying serological dilemmas, reaching final diagnosis and defining status of the infection.

Streptococcus equi subsp. zooepidemicus meningitis.

A 72-year-old woman was hospitalized for Streptococcus equi subsp. zooepidemicus meningitis. The same organism was cultured from her two horses. She denied contact with horses, but had a practice of consuming unpasteurized milk from a cow. The cow was in the same stable as the horses, and the ill woman's son milked the cow.

[Fasciocutaneous flaps in reconstruction of soft tissue defects below the knee]. / Fasciokutani reznjevi u rekonstrukciji mekotkivnih defekata potkolenice.

Reconstruction of soft tissue defects of the lower leg from 1966-2003, using fasciocutaneous flaps is discussed in this paper. Our experience with soft tissues defects in 69 patients is shown here. Different types of fasciocutaneous flaps were used (proximally and distally based fasciocutaneous flap, island, fasciosubcutaneous) based on septocutaneous perforators of all 3 main arterial trunks of the lower leg. We had complete or almost complete necrosis in only 4 patients, whereas in other patients flaps survived. Results obtained using fasciocutaneous flaps, even in reconstruction of war wounds convinced us that fasciocutaneous flaps are reliable method of reconstruction of the soft tissue defects of the lower leg, especially its distal third and regions of malleoli.

[Reconstruction of large defects of the abdominal wall using dermal and synthetic grafts]. / Rekonstrukcije velikih defekata trbusnog zida primenom koznog i sintetskog grafta.

Large defects of abdominal wall (greater than 8 cm in diameter) related to different cause, are still difficult problem of modern surgery. The best results in order to obtain safe and permanent anatomical and functional abdominal wall integrity are reached by autogenous dermal and synthetic grafts. Controversies concerning quality of these procedures are still presents. Our work is based on two equal experimental groups of 20 Vister rats each, with large artificial abdominal wall defects: one treated with autogenous dermal graft, another with synthetic Mersilene mesh graft. The animals from both groups were sacrificed in previous planned time intervals (3rd, 7th, 14th and 48th days). Afterwards detailed microscopic and gross examination of abdominal wall reparation and quality of reconstructed abdominal wall defects had been performed. According to our results both methods are easy to be performed and safety surgical procedures. Overestimated usage of synthetic grafts should be diminished because of advantages of autologous dermal graft--availability, substitution of firmly fibrosis tissue and endurance against infection.

[Hodgkin's lymphoma in children--histopathological and clinical features a 10-year experience (1978-1987)]. / Hockinov (Hodgkin) limfom kod dece--histopatoloske i klinicke karakteristike. Analiza za desetogodisnji period (1978-1987).

Hodgkin's lymphoma (HL) is a common neoplasm in children. In a 10-year period HL was found in 41% of all malignant lymphomas. Clinical and morphological features of 22 cases of HL are presented. HL was clinically manifested as an painless unilateral cervical lymphadenopathy. Males were slightly more affected, and the majority of the patients were from 5 to 15 years old. The most frequent histological types of HL were nodular sclerosis (45%) and mixed cellularity (40%). Although modern chemotherapy altered prognosis of HL and contributed to a favourable outcome of the disease in children, 36% of our patients died.

[Congenital malformation of the ear associated with secretory otitis media]. / Malformation congénitale de l'oreille associée à une otite sécrétoire moyenne.

The authors presented a child with congenital malformation of the ear in whom secretory otitis media (SOM) was discovered during an operation. Histological analysis of the mucous membrane showed an advanced phase of the disease.

Correlation of clinical diagnoses with autopsy findings: a retrospective study of 2,145 consecutive autopsies.

The protocols of 2,145 autopsies were retrospectively reviewed and the findings compared with the clinical diagnoses. A sudden decline in the autopsy rate that occurred during the period studied was followed by a highly statistically significant difference in clinical accuracy (P less than 0.01), in favor of the predecline period. The overall rate of major discrepancies was 29 per cent. The most frequently missed diagnoses were infections, which were found in 26 per cent of all autopsies and had not been diagnosed clinically in 63 per cent of these cases. Malignancies occupied second place among overlooked diagnoses in the selected disease categories; in 99 per cent of the cases the malignancy was the principal diagnosis, and it had been misdiagnosed clinically in 42 per cent of these cases. Cerebrovascular disorders were correctly diagnosed in most cases (87 per cent of the patients in this group). Among autopsy diagnoses labeled as the immediate causes of death, the most frequently overlooked were pulmonary embolism and gastrointestinal hemorrhage, which were not recognized in 84 and 78 per cent, respectively. In cases in which clinicians were not entirely confident in their impressions, their diagnoses were usually confirmed at autopsy. In these cases 15 per cent of the patients died soon after admission to the hospital, with accurate diagnoses in 71 per cent. The discrepancies disclosed should be regarded as sufficiently large to mandate continued emphasis on autopsy evaluation as the basis for the control of the quality of patient care.

Differential diagnosis of undifferentiated malignant tumors with monoclonal antibody T29/33.

An immunoperoxidase method for distinguishing lymphomas from nonlymphoid neoplasms with monoclonal antibody T29/33 is described. This antibody recognizes a 200,000-dalton pan-hematopoietic glycoprotein antigen. Staining in nearly 200 hematopoietic tumors was positive for T29/33, although three of six plasmacytomas were negative for this antibody. Five undifferentiated tumors that were proved to be lymphomas by subsequent electron microscopic and immunohistologic studies were positive for T29/33. Conversely, 11 of 12 undifferentiated tumors with ultrastructural and clinical features of carcinoma or sarcoma were T29/33-negative. The only exception was one sarcoma that was T29/33-positive. Thus, monoclonal antibody T29/33 is a valuable tool for characterizing neoplasms that cannot be diagnosed by histopathologic examination alone.

Immunoblastic sarcoma in patients with systemic lupus erythematosus-like disorders.

Five patients, predominantly older men, had abnormal immune states for prolonged periods of time with manifestations of multisystem involvement, including features of systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. In the course of their disease, all had malignant lymphoma (immunoblastic sarcoma) develop. The development of lymphoma was associated with generalized lymphadenopathy in four cases.

[Morphologic analysis of a case of Sheehan's postpartal hypophyseal necrosis]. / Morfoloska analiza jednog slucaja Sheehanove postpartalne nekroze hipofize.

The post-mortem finding of a 39-year-old woman with the Sheehan postpartal necrosis of the hypophysis is described. This was the only such case of 16,580 obductions of women in the period from 1961 to 1976. The cause of death was cerebral encephalomalacia and non-specific bronchopneumonia. The death occurred five years after the last delivery and almost three years after the established clinical diagnosis.