Cluster analysis of long COVID symptoms for deciphering a syndrome and its long-term consequence.

The long-term symptoms of COVID-19 are the subject of public and scientific discussions. Understanding how those long COVID symptoms co-occur in clusters of syndromes may indicate the pathogenic mechanisms of long COVID. Our study objective was to cluster the different long COVID symptoms. We included persons who had a COVID-19 and assessed long-term symptoms (at least 4 weeks after first symptoms). Hierarchical clustering was applied to the symptoms as well as to the participants based on the Euclidean distance h of the log-values of the answers on symptom severity. The distribution of clusters within our cohort is shown in a heat map.From September 2021 to November 2023, 2371 persons with persisting long COVID symptoms participated in the study. Self-assessed long COVID symptoms were assigned to three symptom clusters. Cluster A unites rheumatological and neurological symptoms, cluster B includes neuro-psychological symptoms together with cardiorespiratory symptoms, and a third cluster C shows an association of general infection signs, dermatological and otology symptoms. A high proportion of the participants (n = 1424) showed symptoms of all three clusters. Clustering of long COVID symptoms reveals similarities to the symptomatology of already described syndromes such as the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) or rheumatological autoinflammatory diseases. Further research may identify serological parameters or clinical risk factors associated with the shown clusters and might improve our understanding of long COVID as a systemic disease. Furthermore, multimodal treatments can be developed and scaled for symptom clusters and associated impairments.

Audiological profile of adult Long COVID patients.

INTRODUCTION: Hearing loss is one of the self-reported symptoms of Long COVID patients, however data from objective and subjective audiological tests demonstrating diminished hearing in Long COVID patients has not been published. MATERIALS AND METHODS: Respondents of a large Long COVID online survey were invited to the ENT-department for an otologic exam. The participants were split into three groups based on their history of SARS-CoV-2 infection and persistence of symptoms. Respondents with a history of a SARS-CoV-2 infection were allocated to the Long COVID group, if they reported persistent symptoms and to the Ex COVID group, if they had regained their previous level of health. Participants without a history of SARS-CoV-2 infection made up the No COVID control group. In total, 295 ears were examined with otoscopy, tympanograms, pure tone audiometry and otoacoustic emissions. Ears with known preexisting hearing loss or status post ear surgery, as well as those with abnormal otoscopic findings, non-type A tympanograms or negative Rinne test were excluded. RESULTS: Compared to the No COVID and Ex COVID groups, we did not find a clinically significant difference in either hearing thresholds or frequency specific TEOAEs. However, at 500 Hz the data from the left ear, but not the right ear showed a significantly better threshold in the Ex COVID group, compared to Long COVID and No COVID groups. Any of the other tested frequencies between 500 Hz and 8 kHz were not significantly different between the different groups. There was a significantly lower frequency-specific signal-to-noise-ratio of the TEOAEs in the Long COVID compared to the No COVID group at 2.8 kHz. At all other frequencies, there were no significant differences between the three groups in the TEOAE signal-to-noise-ratio. CONCLUSION: This study detected no evidence of persistent cochlear damage months after SARS-CoV-2 infection in a large cohort of Long COVID patients, as well as those fully recovered.

[Hepatitis A immunity in refugees in Germany during the current exodus]. / Hohe Hepatitis-A-Immunitätsrate bei Flüchtlingen in Deutschland.

BACKGROUND: Germany is facing a huge humanitarian challenge with rapidly rising numbers of refugees entering the country. Data on hepatitis A seroprevalence and infection in refugees and asylum seekers in Europe during the current refugee exodus is scarce. OBJECTIVES: To assess hepatitis A (HAV) seroprevalence and immunity in refugees arriving in northern Germany in 2015. MATERIALS AND METHODS: A cross-sectional study of 235 refugees seeking shelter in reception centers in Northern Germany in August 2015 was performed, as acute Hepatitis A had been detected in one refugee in this camp. In order to analyze acute HAV infection and overall immunity, serological screening for HAV antibodies (combined IgG and IgM) was performed. The immunity threshold was defined as <20 IU/l. In all positive screening results, separate IgM testing was performed to detect acute infections. RESULTS: Males accounted for 84.3 % of HAV screened refugees and the mean age of refugees was 29.1 ± 11.2 years. Children and adolescents below the age of 18 years made up 8.8 % of the migrants. Overall HAV immunity within the cohort was 90 %, and a mild age-dependent increase in HAV immunity was observed, with 81.1 % immunity in children <18 years and a 100 % seropositivity in subjects >50 years. One 20-year-old female refugee had positive IgM results with high HAV antibodies, most likely due to subacute HAV infection. CONCLUSIONS: This comparably high rate of HAV protected refugees in our cohort supports the notion that the probability of large HAV outbreaks in current German refugee centers is low. However, depending on their current living situation, HAV vaccination should be considered for each refugee child, and healthcare providers and personnel working in refugee centers should be vaccinated against HAV.

[Low seroprevalence of syphilis and HIV in refugees and asylum seekers in Germany in 2015]. / Niedrige Seroprävalenz von Syphilis und HIV bei Flüchtlingen in Deutschland im Jahr 2015.

Background | Currently only estimates exist of seroprevalence of syphilis and human immunodeficiency virus (HIV) in refugees arriving in Germany during the current refugee crisis. Objectives | To assess the prevalence of syphilis and human immunodeficiency virus (HIV) in refugees arriving in northern Germany in 2015. Materials and methods | In a cross-sectional study in 790 patients from all age groups tests for serological markers of treponema pallidum and in 789 patients for human immunodeficiency virus (HIV) were performed in August 2015 in reception centers in northern Germany. Results | The overall prevalence of treponema pallidum antibodies was 0.13 % (1/790; [95 % CI: 0 - 0.4]). HIV antibodies were positive in two refugees from sub-Saharan Africa (2/789; 0.25 %, [95 % CI: 0 - 0.6]). Conclusions | This study showed a low prevalence of treponema pallidum antibodies and human immunodeficiency virus infection (HIV) in a German refugee cohort, not significantly different from German controls.

Surgery decreases number of cells secreting cytotoxic mediators and increases secretion of interleukin 10 in patients with lung cancer.

AIMS: The phenomenon of immunosuppression induced by surgery is widely described as the adverse impact of surgical interventions on leukocytes' populations and secretion of several cytokines. Best of our knowledge, we present the first report evaluating the effect of surgical treatment on the specific anti-cancer immune response against tumour antigens. METHODS: The study included 30 patients operated on for lung cancer. Specific secretion of IFN-γ, Granzyme B, perforines, IL-4, IL-5, IL-10, IL-17a was assessed by ELISPOT (Enzyme-Linked Immunosorbent Spot Assay). RESULTS: Number of cells secreting IFN-γ, Granzyme B and perforines under the influence of autologous tumour antigens or mitogens was significantly decreased on the first day after surgery. During the postoperative recovery we observed an increase in the number of cells secreting IFN-γ, but on the 7th day it still remained lower than before the operation. On the 28th postoperative day it reached a level which was not significantly higher than before the surgery. On the 1st and 7th postoperative day we discovered a significant increase in IL-10 secretion, in response to autologous tumour antigens. CONCLUSIONS: Our results suggest an immunosuppressive effect of surgery on the specific and nonspecific immune stimulation. This effect is particularly expressed in relation to Th1-type immunological response which is associated with direct elimination of cancer cells. Another unfavourable observation is elevated secretion of immunosuppressive IL-10 in response to cancer antigens. These phenomena are associated with shorter survival of the patients.

[Differential diagnosis of inflammatory arthritis of the hip joint]. / Differentialdiagnose der entzündlichen Arthritis des Hüftgelenks.

The differential diagnosis of inflammatory arthritis of the hip covers a broad spectrum and includes in particular crystal arthropathies and systemic rheumatic diseases. The clinical examination of joint effusion of the hip may be difficult but diagnostic ultrasound should support an early diagnosis. Radiographs remain essential in the initial diagnostic evaluation but may be of limited value in early stages of the disease. Magnet resonance imaging may be helpful in addition for the detection of early arthritis.Basic laboratory diagnostics include blood count, determination of C-reactive protein level and erythrocyte sedimentation rate. If septic arthritis is suspected blood cultures should be taken. Joint aspiration should be attempted in all cases and especially in monoarthritis. Synovial fluid analysis includes white cell count, differential count, examination for crystals and microbiological diagnostics including direct stains and cultures. The most important differential diagnoses of inflammatory arthritis of the hip joint in adults are osteoarthritis, crystal arthropathies and systemic rheumatic diseases, such as spondyloarthritis.

Survivin antiapoptotic gene expression as a prognostic factor in non-small cell lung cancer: in situ hybridization study.

Survivin is an inhibitor of apoptosis that plays a significant role in cell cycle regulation and is important for survival prognosis in many neoplasms. Survivin expression was assessed by in situ hybridization (ISH) in 60 consecutive patients (54 males and 4 females) with NSCLC treated between 1993 and 1997. The examined patients had IIB and IIIA stage according to TNM system. In all cases the chemotherapy with cisplatin and etoposide (2 cycles) was administered prior the surgery; in patients responding to the therapy one more cycle was applied. Survivin gene overexpression was observed in 35 patients (58.3%). There was no correlation between survivin mRNA level and histological type of tumor, stage of cell differentiation, stage of disease according to TNM classification, performance status according to WHO and number of chemotherapy regimens administered (p > 0.05). However, the correlation between survivin gene expression and response to the chemotherapy was statistically significant (p = 0.04). Statistical analysis showed that median survival in patients with survivin gene overexpression was shorter (14.0 months) as compared to patients with no expression (60.0 months; p = 0.00002). In survival assessment by means of Kaplan-Meier test, 14.3% of five-year survival was achieved in the former group versus 60% in the latter (p = 0.00003). Univariate analysis (log-rank test) showed that significant independent prognostic factors in NSCLC included: stage of the disease according to TNM classification (p = 0.006), response to chemotherapy (p = 0.005) and pattern of survivin gene expression (p = 0.00003). Multivariate analysis utilizing Cox's model showed that for survival assessment the stage according to TNM, response to the chemotherapy and survivin expression estimated by means of ISH are of statistical significance (p=0.00001). The calculated predictive values showed that ISH technique was quite accurate in assessment of five-year survival. Our data show that survivin expression may be used as a prognostic factor and a target for therapy.

Principles of induction chemotherapy for non-small cell lung cancer.

The results of lung cancer treatment have not significantly improved for many years. About 35% of patients with non-small cell lung cancer (NSCLC) are in clinical stage IIIA. Clinically asymptomatic distant metastases occur in the majority of these patients. In such cases only combined treatment offers a chance of cure. In the Chest Surgery Center in Lublin a clinical trial was carried out aimed to assess late results of combined treatment in patients with IIIA NSCLC. Over 700 patients were enrolled in the study. The results of the trial disclosed, that neoadjuvant chemotherapy prolonged life of the operated patients and improved their life quality. However, a question of qualification for this complex treatment and complexity of assessment criteria, still remain to be answered.

Guidance of anticoagulation after intracoronary implantation of Palmaz-Schatz stents by monitoring prothrombin and prothrombin fragment 1 + 2.

The primary objective of this study was to apply a sophisticated coagulation monitoring system including estimation of the concentration of prothrombin fragment 1 + 2 (PTF 1 + 2) and the activity of prothrombin (coagulation factor II or FII) to cases of stent implantation and to compare the results with those of standard coagulation tests. The secondary objective was to detect the incidence after stenting of subacute thrombosis (SAT) and bleeding complications in these patients and to compare the results with those of a group of patients with stent implantation in whom coagulation was monitored exclusively by standard tests. SAT several days after coronary stenting occurs in up to 20% despite aggressive intravenous and overlapping oral anticoagulation. According to a prospective study protocol 120 consecutive patients with implantation of 155 Palmaz-Schatz stents underwent coagulation monitoring including single daily estimation of the concentration of PTF1 + 2 (target range < 0.5 nmol/L) and of FII activity (15% to 35%) in addition to the standard tests of thrombin time (TT), partial thromboplastin time (aPTT), international normalized ratio (INR), antithrombin III (ATIII), and fibrinogen. Adjustment of heparin and phenprocoumon dosages in this study group was based only on the results of PTF1 + 2 and FII measurements. A control group consisted of 53 patients with implantation of 64 stents who were matched for baseline, angiographic, and procedure-related characteristics. After stenting, anticoagulation was monitored by estimation of TT (target range > 70 seconds), aPTT (> 70 seconds), INR (3.0 to 4.5), AT III (> 80%), and fibrinogen (< 450 mg/dl) in this control group. There was a weak correlation between PTF1 + 2 and aPTT (r = 0.337; PTF1 + 2 = -0.00169aPTT + 0.491) and PTF1 + 2 and TT (r = 0.328; PTF1 + 2 = -0.00142TT + 0.494). A better correlation was found between FII and INR (r = 0.983; FII = -23.8 INR + 134). Stable oral anticoagulation was maintained 2.8 +/- 0.9 days later according to an FII concentration of < 35% compared with an INR > 3. The incidence of SAT was 3.3% with 3.0% for elective versus 3.8% for nonelective stenting. The sensitivity, specificity, and accuracy of the PTF1 + 2 test were 100%, 88%, and 88%, respectively. In the control group the incidence of SAT was 17%, with 16.1% for elective versus 18% for nonelective stenting. Major bleeding complications occurred in 10% (study group) and in 11.3% (control group) of patients (no statistical difference).(ABSTRACT TRUNCATED AT 400 WORDS)

Some morphological and hormonal aspects of ovulation and superovulation in the rat.

In the first experiment, mature female Wistar rats, displaying a regular 4-day oestrous cycle, were killed in succession every 2 or 3 h on the day of pro-oestrus and oestrus until the time of ovulation. In the second experiment, immature female Wistar rats (aged 24 days) were injected s.c. with 30 IU pregnant mare serum gonadotrophin (PMSG) and 56 h later with 20 IU human chorionic gonadotrophin (hCG). They were killed in groups at 0, 24, 48, 56 and 57 h, and then every 2 h until 72 h. Excised ovaries were homogenized and analysed for steroid content or they were submitted to a routine histological procedure. The cyclic and PMSG/hCG-treated rats exhibited some similarities and differences in the general pattern of steroid content. Either a presumptive endogenous LH surge or administration of hCG resulted in an increase in the ovarian androgen concentration which preceded a rise in progesterone; the progesterone peak, in turn, was accompanied by a fall in the amount of androgens and oestradiol. However, in comparison with cyclic rats, superovulated animals displayed a significantly higher ovarian androgen level for a prolonged period; ovarian oestradiol concentration was also raised while the progesterone content was much lower. Histological analysis revealed large differences between the ovaries of superovulated and cyclic rats, especially with regard to the maturing follicles. The majority of PMSG/hCG-derived follicles showed hypertrophied theca interna and degenerated or luteinized granulosa. A large number of preovulatory follicles did not ovulate. These results clearly indicate that PMSG/hCG-induced follicles are not equal to the follicles developing during a normal oestrous cycle. This should be taken into consideration when using superovulated animals in experiments.

The influence of Ambroxol on peroxidative processes in lung and plasma in dogs after pulmonectomy.

The purpose of the studies was to determine the effect of Ambroxol on the activity of antioxidant enzymes and on the glutathione level as well as the intensity of the peroxidative processes in the lung tissue, alveolar macrophages and plasma in dogs after unilateral pulmonectomy. On the 2nd and 6th day after the surgery the activity of antioxidant enzymes and the glutathione level were studied in the remaining lung. The levels of the lipid peroxidation products were determined in the analogous system. In both examined groups the increase in the antioxidant enzyme activity and the lipid peroxidation product levels was observed in the remaining lung after the surgery. In Ambroxol-treated animals the statistically significant increase in the antioxidant enzyme activity was noted while the intensity of peroxidative processes was found to be lower. This fact may suggest that Ambroxol stimulates the resistance of the lung tissue to the free radical activity and inhibits the lung peroxidative processes in dogs after pulmonectomy.

[Effect of ambroxol on surfactant lipids in patients after resection of pulmonary tissue]. / Wplyw ambroxolu na lipidy surfaktantu u chorych po wycieciu miazszu plucnego.

Effect of Ambroxol on phospholipids and higher fatty acids of pulmonary surfactant was studied in patients with lung cancer undergoing pulmonary resection. Intravenous administration of Ambroxol was carried out for 8 days in a dose 1000 mg per day before pulmonary resection. It produced elevation of disaturated phosphatidylcholine and the general level of phosphatidylcholine. Also increase of palmitic acid and saturated fatty acids of the phospholipid fraction was found. The results of this study show that Ambroxol on a short time elevates levels of active substances of pulmonary surfactant and decreases the destructive processes of pulmonary parenchyma.