Derivation and Internal Validation of a Novel Risk Assessment Tool to Identify Infants and Young Children at Risk for Post-Discharge Mortality in Dar es Salaam, Tanzania and Monrovia, Liberia.

OBJECTIVE: To derive and validate internally a novel risk assessment tool to identify young children at risk for all-cause mortality ≤60 days of discharge from hospitals in sub-Saharan Africa. STUDY DESIGN: We performed a prospective observational cohort study of children aged 1-59 months discharged from Muhimbili National Hospital in Dar es Salaam, Tanzania and John F. Kennedy Medical Center in Monrovia, Liberia (2019 to 2022). Caregivers received telephone calls up to 60 days after discharge to ascertain participant vital status. We collected socioeconomic, demographic, clinical, and anthropometric data during hospitalization. Candidate variables with P<0.20 in bivariate analyses were included in a multivariable logistic regression model with best subset selection to identify risk factors for the outcome. We internally validated our tool using bootstrapping with 500 repetitions. RESULTS: There were 1,933 young children enrolled in the study. The median (interquartile range) age was 11 (4, 23) months and 58.7% were male. In total, 67 (3.5%) died during follow-up. Ten variables contributed to our tool (total possible score 82). Cancer (adjusted odds ratio [aOR] 10.6, 95% CI 2.58, 34.6), pedal edema (aOR 6.94, 95% CI 1.69, 22.6), and leaving against medical advice (aOR 6.46, 95% CI 2.46, 15.3) were most predictive of post-discharge mortality. Our risk assessment tool demonstrated good discriminatory value (optimism corrected area under the receiver operating characteristic curve 0.77), high precision, and sufficient calibration. CONCLUSIONS: After validation, this tool may be used to identify young children at risk for post-discharge mortality to direct resources for follow-up of high-risk children.

Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome.

BACKGROUND: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. OBJECTIVES: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. METHODS: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5'-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). RESULTS: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709). CONCLUSION: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.

Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Major depression (MDD) and bipolar disorder (BD) are linked to immune activation, increased oxidative stress, and lower antioxidant defenses. OBJECTIVES: To systematically review and meta-analyze all data concerning biomarkers of reverse cholesterol transport (RCT), lipid-associated antioxidants, lipid peroxidation products, and autoimmune responses to oxidatively modified lipid epitopes in MDD and BD. METHODS: Databases including PubMed, Google scholar and SciFinder were searched to identify eligible studies from inception to January 10th, 2023. Guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: The current meta-analysis included 176 studies (60 BD and 116 MDD) and examined 34,051 participants, namely 17,094 with affective disorders and 16,957 healthy controls. Patients with MDD and BD showed a) significantly decreased RCT (mainly lowered high-density lipoprotein cholesterol and paraoxonase 1); b) lowered lipid soluble vitamins (including vitamin A, D, and coenzyme Q10); c) increased lipid peroxidation and aldehyde formation, mainly increased malondialdehyde (MDA), 4-hydroxynonenal, peroxides, and 8-isoprostanes; and d) Immunoglobulin (Ig)G responses to oxidized low-density lipoprotein and IgM responses to MDA. The ratio of all lipid peroxidation biomarkers/all lipid-associated antioxidant defenses was significantly increased in MDD (standardized mean difference or SMD = 0.433; 95% confidence intervals (CI): 0.312; 0.554) and BD (SMD = 0.653; CI: 0.501-0.806). This ratio was significantly greater in BD than MDD (p = 0.027). CONCLUSION: In MDD/BD, lowered RCT, a key antioxidant and anti-inflammatory pathway, may drive increased lipid peroxidation, aldehyde formation, and autoimmune responses to oxidative specific epitopes, which all together cause increased immune-inflammatory responses and neuro-affective toxicity.

The tryptophan catabolite or kynurenine pathway in schizophrenia: meta-analysis reveals dissociations between central, serum, and plasma compartments.

The tryptophan catabolite (TRYCAT) pathway is implicated in the pathophysiology of schizophrenia (SCZ) since the rate-limiting enzyme indoleamine-dioxygenase (IDO) may be induced by inflammatory and oxidative stress mediators. This systematic review searched PubMed, Web of Science, and Google Scholar for papers published from inception until August 2021 and meta-analyzed the association between SCZ and TRYCATs in the central nervous system (CNS) and peripheral blood. We included 61 studies comprising 2813 patients and 2948 healthy controls. In the CNS we found a significant (p < 0.001) increase in the kynurenine/tryptophan (KYN/TRP) (standardized mean difference, SMD = 0.769, 95% confidence interval, CI: 0.456; 1.082) and kynurenic acid (KA)/KYN + TRP (SMD = 0.697, CI: 0.478-0.917) ratios, KA (SMD = 0.646, CI: 0.422; 0.909) and KYN (SMD = 1.238; CI: 0.590; 1.886), while the 3OH-kynurenine (3HK) + KYN-3-monooxygenase (KMO)/KYN ratio was significantly reduced (SMD = -1.089, CI: -1.682; -0.496). There were significant differences between KYN/TRP, (KYN + KA)/TRP, (3HK + KMO)/KYN, KA, and KYN levels among the CNS and peripheral blood, and among serum and plasma KYN. The only useful peripheral marker of CNS TRYCATs findings was the increased KYN/TRP ratio in serum (SMD = 0.211, CI: 0.056; 0.366, p = 0.007), but not in plasma. There was no significant increase in a neurotoxic composite score based on KYN, 3HK, and picolinic, xanthurenic, and quinolinic acid. SCZ is accompanied by increased IDO activity in the CNS and serum, and reduced KMO activity and a shift towards KA production in the CNS. This CNS TRYCATs profile indicates neuroprotective, negative immunoregulatory and anti-inflammatory effects. Peripheral blood levels of TRYCATs are dissociated from CNS findings except for a modest increase in serum IDO activity.

The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is accompanied by activated immune-inflammatory pathways and oxidative stress, which both induce indoleamine-2,3-dioxygenase (IDO), a key enzyme of the tryptophan (TRP) catabolite (TRYCAT) pathway. The aim of this study was to systematically review and meta-analyze the status of the TRYCAT pathway, including the levels of TRP and kynurenine (KYN) and the activity of IDO, as measured by the ratio of KYN/TRP. METHODS: This systematic review searched PubMed, Google Scholar, and Web of Sciences and included 14 articles that compared TRP and tryptophan catabolites (TRYCATs) in COVID-19 patients versus non-COVID-19 controls, as well as severe/critical versus mild/moderate COVID-19. The analysis was done on a total of 1269 people, including 794 COVID-19 patients and 475 controls. RESULTS: The results show a significant (p < 0.0001) increase in the KYN/TRP ratio (standardized mean difference, SMD = 1.099, 95% confidence interval, CI: 0.714; 1.484) and KYN (SMD = 1.123, 95% CI: 0.730; 1.516) and significantly lower TRP (SMD = - 1.002, 95%CI: - 1.738; - 0.266) in COVID-19 versus controls. The KYN/TRP ratio (SMD = 0.945, 95%CI: 0.629; 1.262) and KYN (SMD = 0.806, 95%CI: 0.462; 1.149) were also significantly (p < 0.0001) higher and TRP lower (SMD = - 0.909, 95% CI: - 1.569; - 0.249) in severe/critical versus mild/moderate COVID-19. No significant difference was detected in kynurenic acid (KA) and the KA/KYN ratio between COVID-19 patients and controls. CONCLUSIONS: Our results indicate increased activity of the IDO enzyme in COVID-19 and severe/critical patients. The TRYCAT pathway is implicated in the pathophysiology and progression of COVID-19 and may signal a worsening outcome of the disease.

Predictors and outcome of time to presentation among critically ill paediatric patients at Emergency Department of Muhimbili National Hospital, Dar es Salaam, Tanzania.

BACKGROUND: Mortality among under-five children in Tanzania remains high. While early presentation for treatment increases likelihood of survival, delays to care are common and factors causing delay to presentation among critically ill children are unknown. In this study delay was defined as presentation to the emergency department of tertially hospital i.e. Muhimbili National Hospital, more than 48 h from the onset of the index illness. METHODOLOGY: This was a prospective cohort study of critically ill children aged 28 days to 14 years attending emergency department at Muhimbili National Hospital in Tanzania from September 2019 to January 2020. We documented demographics, time to ED presentation, ED interventions and 30-day outcome. The primary outcome was the association of delay with mortality and secondary outcomes were predictors of delay among critically ill paediatric patients. Logistic regression and relative risk were calculated to measure the strength of the predictor and the relationship between delay and mortality respectively. RESULTS: We enrolled 440 (59.1%) critically ill children, their median age was 12 [IQR = 9-60] months and 63.9% were males. The median time to Emergency Department arrival was 3 days [IQR = 1-5] and more than half (56.6%) of critically ill children presented to Emergency Department in > 48 h whereby being an infant, self-referral and belonging to poor family were independent predictors of delay. Infants and those referred from other facilities had 2.4(95% CI 1.4-4.0) and 1.8(95% CI 1.1-2.8) times increased odds of presenting late to the Emergency Department respectively. The overall 30-day in-hospital mortality was 26.5% in which those who presented late were 1.3 more likely to die than those who presented early (RR = 1.3, CI: 0.9-1.9). Majority died > 24 h of Emergency Department arrival (P-value = 0.021). CONCLUSION: The risk of in-hospital mortality among children who presented to the ED later than 48 h after onset of illness was 1.3 times higher than for children who presented earlier than 48 h. It could be anywhere from 10% lower to 90% higher than the point estimate. However, the effect size was statistically not significant since the confidence interval included the null value Qualitative and time-motion studies are needed to evaluate the care pathway of critically ill pediatric patients to identify preventable delays in care.

Predictors and outcome of cardiac arrest in paediatric patients presenting to emergency medicine department of tertiary hospitals in Tanzania.

BACKGROUND: The survival of children who suffer cardiac arrest is poor. This study aimed to determine the predictors and outcome of cardiac arrest in paediatric patients presenting to an emergency department of a tertiary hospital in Tanzania. METHODOLOGY: This was a prospective cohort study of paediatric patients > 1 month to ≤ 14 years presenting to Emergency Medicine Department of Muhimbili National Hospital (EMD) in Tanzania from September 2019 to January 2020 and triaged as Emergency and Priority. We enrolled consecutive patients during study periods where patients' demographic and clinical presentation, emergency interventions and outcome were recorded. Logistic regression analysis was performed to identify the predictors of cardiac arrest. RESULTS: We enrolled 481 patients, 294 (61.1%) were males, and the median age was 2 years [IQR 1-5 years]. Among studied patients, 38 (7.9%) developed cardiac arrest in the EMD, of whom 84.2% were ≤ 5 years. Referred patients were over-represented among those who had an arrest (84.2%). The majority 33 (86.8%) of those who developed cardiac arrest died. Compromised circulation on primary survey (OR 5.9 (95% CI 2.1-16.6)), bradycardia for age on arrival (OR 20.0 (CI 1.6-249.3)), hyperkalemia (OR 8.2 (95% CI 1.4-47.7)), elevated lactate levels > 2 mmol/L (OR 5.2 (95% CI 1.4-19.7)), oxygen therapy requirement (OR 5.9 (95% CI 1.3-26.1)) and intubation within the EMD (OR 4.8 (95% CI 1.3-17.6)) were independent predictors of cardiac arrest. CONCLUSION: Thirty-eight children developed cardiac arrest in the EMD, with a very high mortality. Those who arrested were more likely to present with signs of hypoxia, shock and acidosis, which suggest they were at later stage in their illness. Outcomes can be improved by strengthening the pre-referral care and providing timely critical management to prevent cardiac arrest.

Schizophrenia phenomenology revisited: positive and negative symptoms are strongly related reflective manifestations of an underlying single trait indicating overall severity of schizophrenia.

BACKGROUND: To examine whether negative symptoms, psychosis, hostility, excitation, and mannerism (PHEM symptoms), formal thought disorders (FTD) and psychomotor retardation (PMR) are interrelated phenomena in major neurocognitive psychosis (MNP) or deficit schizophrenia and whether those domains belong to an underlying latent vector reflecting general psychopathology. METHODS: In this study, we recruited 120 patients with MNP or deficit schizophrenia and 54 healthy subjects and measured the above-mentioned symptom domains. RESULTS: In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that positive (and PHEM or psychotic) and negative symptoms greatly overlap and probably measure the same latent construct. Soft independent modeling of class analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms. CONCLUSIONS: In stable phase MNP, which is a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of "positive" and "negative" symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its reflective manifestations are the key factors of schizophrenia phenomenology.

Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-Dependent ß-Thalassemia Major Patients.

Patients with ß-thalassemia major (ß-TM) show ineffective erythropoiesis and iron overload, which is the leading cause of mortality and organ injury. The present study aimed to investigate the relationships between two iron regulatory hormones, hepcidin and erythroferrone (ERFE) levels, and iron status parameters in Iraqi patients with ß-TM. Iron status parameters and hormones were measured in 60 patients and compared with 30 healthy controls. The results indicated significant changes in different iron status parameters, while ferritin with the ∼11-fold increase showed the most change. Significant reduction in hepcidin and an increase in ERFE levels were detected in patients when compared to the control group, while no direct correlation was identified with the other measured iron status parameters. The receiver operating characteristic (ROC) analysis showed that the z-score of the composite of ERFE + ferritin has a full diagnostic ability for ß-TM. In conclusion, our findings indicated the correlation between different iron status parameters and ferritin as the leading predictor of iron overload and two main iron regulatory hormones.

Effect of Low-Dose Nano Titanium Dioxide Intervention on Cd Uptake and Stress Enzymes Activity in Cd-Stressed Cowpea [Vigna unguiculata (L.) Walp] Plants.

Cadmium contamination of agricultural soils is a serious problem due to its toxic effects on health and yield of crop plants. This study investigates the potential of low-dose nano-TiO2 as soil nanoremediation on Cd toxicity in cowpea plants. To achieve this goal, cowpea seeds were germinated on Cd-spiked soils at 10 mg/kg for 14 days and later augmented with 100 mg nTiO2/kg (nTiO2-50 nm and bTiO2-68 nm, respectively). The results showed that chlorophylls were not altered by nano-TiO2 intervention. Cadmium partitioning in roots and leaves was reduced by the applied nano-TiO2 but significantly higher than control. Ascorbate peroxidase and catalase activities in roots and leaves were promoted by nano-TiO2 intervention compared to control and sole Cd, respectively. However, magnitudes of activity of enzyme activities were higher in nTiO2 compared to bTiO2 treatments. The enhanced enzymes activity led to reduced malonaldehyde content in plant tissues. The study concludes that soil application of nano-TiO2 could be a green alternative to ameliorate soil Cd toxicity in cowpea plants.

[Reconstruction of the examination of the laryngeal carcinoma of Emperor Frederick III by Rudolf Virchow]. / Rekonstruktion der Befundung des Larynxkarzinoms Kaiser Friedrichs III. durch Rudolf Virchow.

Rudolf Virchow is one of the founders of modern pathology, and many of his ideas on inflammatory and neoplastic diseases are still valid today. Even for Virchow, determination of malignancy was not always easy. As an example, the laryngeal disease of Crown Prince Frederick William, the later Emperor Frederick III, is presented.The clinical findings at the beginning of the disease were suggestive of a carcinoma, though an inflammatory lesion was also discussed. Several attempts were made to remove the lesion bioptically, but local recurrences occurred and the first tissue samples were not examined histopathologically. Since laryngeal tumour operations had a high mortality at that time, histopathologic examinations were made in order to decide for or against an operation. The samples taken after pre-treatment did not meet Virchow's criteria for determining a carcinoma. Contrary to the present concept of a carcinoma in situ-carcinoma sequence, Virchow's concept was based on the assumption that carcinomas are not derived from the epithelium, but arise from a mesenchymal-epithelial transformation from the connective tissue. The clinical suspicion of a laryngeal carcinoma was confirmed only shortly before the patient's death and later by a post-mortem examination.The question repeatedly asked is whether Virchow should have diagnosed a carcinoma at the beginning of the disease. The answer has been the same for more than a hundred years: the clinician is dissatisfied with the histopathological diagnosis, so the pathologist is to blame.

[Clinical and pathological characteristics of intravascular lymphomas]. / Klinische und pathologische Charakteristika intravaskulärer Lymphome.

Intravascular B­cell lymphomas (IVL) are rare neoplasms that can manifest at any age (mean age ~62-63 years). About half of the cases are associated with Epstein-Barr virus. The most common sites of manifestation are the brain, skin, and bone marrow. The diagnosis is difficult due to unspecific clinical presentation and laboratory changes. FACS (fluorescence-activated cell sorting) and clonality analysis from peripheral blood and radiological findings are often not diagnostic. The most sensitive and most specific diagnostic method is the histopathological and immunohistochemical evaluation of a tissue biopsy. Because of the rarity of this disease, little is known about therapy and prognosis, whereby therapy is mainly similar to non-IVL lymphomas. The prognosis is poor; median survival after diagnosis is approximately one year.

[Injury patterns in interstitial lung diseases]. / Schädigungsmuster interstitieller Lungenerkrankungen.

Interstitial lung diseases (ILD) consist of a complex group of hundreds of non-neoplastic pulmonary diseases with divergent clinical presentation, morphology and progression tendency. This great number of clinical entities contrasts with a limited number of injury patterns. By definition, an adequate classification requires a synopsis of the clinical, radiological and morphological findings. The ATS/ERS (American Thoracic Society/ European Respiratory Society) guidelines recommend an open lung biopsy if high-resolution computed tomography does not provide conclusive results. Due to the focal nature and overlapping features of injury patterns, microscopic categorization is not always possible. In order to broaden the diagnostic criteria by using molecular patterns the Lung Research Working Group of the Institute of Pathology of Hannover Medical School, Europe's leading transplant center, is working up fresh explanted human lungs in a standardized manner. These fresh specimens are used for translational research by means of functional, morphological and molecular techniques in order to identify disease-specific regulatory processes and to make them usable diagnostically and therapeutically.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.

[Pathoanatomical and clinical aspects of the placenta in preterm birth]. / Pathologisch-anatomische und klinische Aspekte der Plazenta bei Frühgeburt.

BACKGROUND: Prematurely born children show a clearly elevated risk for perinatal morbidity, long-term pediatric morbidities and development of chronic diseases in adulthood compared to babies born at term. The pathoanatomical investigation of placentas from preterm births is useful for assessing the etiology, the risk of recurrence and the prognosis for the child. AIMS: The focus is on presenting the clinical and pathoanatomical characteristics of acute chorioamnionitis as a frequent cause of preterm induction of labor and pregnancy-induced hypertension, in particular preeclampsia as a frequent reason for elective cesarean section. Other lesions, sometimes of unclear etiology associated with preterm birth and substantially elevated risk of recurrence are reviewed. The clinical correlations and therapeutic options of the various diseases are discussed taking the risk of recurrence into consideration. MATERIAL AND METHODS: Examination of placentas, association with the clinical course and a literature search. RESULTS AND DISCUSSION: Acute chorioamnionitis and omphalovasculitis can be histologically subdivided into different stages which correlate with the clinical severity and the prognosis for the newborn child. Chronic deciduitis, chronic chorioamnionitis, villitis of unknown etiology, massive perivillous fibrin deposition and chronic histiocytic intervillositis are entities of unclear etiology associated with recurrent abortion and preterm birth. Autoimmune diseases and thrombophilia are occasionally associated with these pathologically defined lesions. Pregnancy-associated hypertensive disease and particularly preeclampsia as the cause of intrauterine developmental delay and elective cesarean section often show characteristic pathoanatomical placental lesions, which can give indications for the severity and duration of the disease and the prognosis for the child. Early onset (<34 weeks of gestation) and late onset preeclampsia show clinical and morphological differences. Subsequent pregnancies are classified as being at risk and screening for preeclampsia should be clinically performed.

[Analysis of therapy-relevant receptors in bone marrow carcinosis : Comparison of pathological and clinical parameters]. / Untersuchung von therapierelevanten Rezeptoren bei Knochenmarkkarzinosen : Ein Vergleich pathologischer und klinischer Parameter.

BACKGROUND: Bone marrow carcinosis is a sign of advanced tumor stage with nonspecific clinical and hematological symptoms. Diagnosis is based on bone marrow biopsy and histopathology, but biopsies are not part of the standard work-up in oncological diseases and data on the correlation between clinical presentation and pathological findings are sparse. MATERIAL AND METHODS: In a retrospective single-center study, data from 20 tumor patients with bone marrow carcinosis were analyzed. Bone marrow biopsies were re-evaluated regarding quantity of tumor cells, fibrosis/necrosis, and bone changes. Immunohistochemistry of potential therapy-relevant receptors and PD-L1 was performed. RESULTS: The median age in these 20 patients (13 women, 7 men) was 65 years. The most frequent diagnoses were breast (n = 8) and lung cancer (n = 5). Anemia (94% of patients), thrombocytopenia (72%), and elevated LDH (83%) were frequent findings. The degree of bone marrow infiltration was highly variable and accounted for between 1 and 95% of biopsy space. Significant bone remodeling was present in 14/20 biopsies. No correlation could be found between histological and radiological findings. Treated patients showed some clinical and biochemical improvement, but the overall survival was poor (median 4.5 months, range < 0.5 to 21.5 months). DISCUSSION: Anemia and thrombocytopenia are frequently associated with bone marrow carcinosis, but are nonspecific. The extent of tumor cell infiltration and osteolytic/osteoblastic changes did not correlate with radiological findings. Therapy-relevant target factors should be evaluated, but therapeutic options are often limited and the prognosis is bad.

[Necrotizing funisitis : Histopathological indicator of occult congenital syphilis]. / Nekrotisierende Funikulitis : Histopathologischer Indikator für eine okkulte konnatale Syphilis.

Congenital syphilis is a rare disease in central Europe. Placental changes may be non-specific but a typical finding is necrotizing funisitis of the umbilical cord. In a case report we describe how the histopathological incidental finding of B lymphocyte-rich, necrotizing funisitis led to the diagnosis of a previously unknown Treponema pallidum infection in parents and their newborn child. The pathological suspicion of congenital syphilis, although rare, has implications for the clinical management (serological evaluation of parents and child as well as the social environment, evaluation of viral coinfection and treatment decision) and is a notifiable disease.

Detection and characterization of carbapenemase-producing Enterobacteriaceae in wounded Syrian patients admitted to hospitals in northern Israel.

Since 2013, four hospitals in northern Israel have been providing care for Syrian nationals, primarily those wounded in the ongoing civil war. We analyzed carbapenemase-producing Enterobacteriaceae (CPE) isolates obtained from these patients. Isolate identification was performed using the VITEK 2 system. Polymerase chain reaction (PCR) was performed for the presence of bla KPC, bla NDM, and bla OXA-48. Susceptibility testing and genotyping were performed on selected isolates. During the study period, 595 Syrian patients were hospitalized, most of them young men. Thirty-two confirmed CPE isolates were grown from cultures taken from 30 patients. All but five isolates were identified as Klebsiella pneumoniae and Escherichia coli. Nineteen isolates produced NDM and 13 produced OXA-48. Among a further 29 isolates tested, multilocus sequence typing (MLST) showed that ST278 and ST38 were the major sequence types among the NDM-producing K. pneumoniae and OXA-48-producing E. coli isolates, respectively. Most were resistant to all three carbapenems in use in Israel and to gentamicin, but susceptible to colistin and fosfomycin. The source for bacterial acquisition could not be determined; however, some patients admitted to different medical centers were found to carry the same sequence type. CPE containing bla NDM and bla OXA-48 were prevalent among Syrian wounded hospitalized patients in northern Israel. The finding of the same sequence type among patients at different medical centers implies a common, prehospital source for these patients. These findings have implications for public health throughout the region.

PARTIAL TRISOMY 4p AND PARTIAL MONOSOMY 13q: CASE REPORT AND A LITERATURE REVIEW.

We report on a term first born dichorionic-diamniotic twin with deletion of the distal long arm of chromosome 13, partial trisomy of the short arm of chromosome 4, intrauterine growth retardation, and multiple anomalies including microcephaly, colpocephaly, absent corpus callosum, bulbous tip of the nose, large and low set ears, macroglossia, thin upper lip, double outlet right ventricle, atria/ventricular septal defect, cleft mitral valve, pulmonary stenosis, single umbilical artery, multicystic dysplastic left kidney, sacral dimple, anterior displacement of anus, simian creases, abnormal thumb (congenital clasped thumb), overlapping toes, and congenital hypothyroidism. This is the first report of a patient with partial trisomy 4p and partial monosomy 13q.

Osteocraniosplenic Syndrome-Hypomineralized Skull with Gracile Long Bones and Splenic Hypoplasia: A Case Report and Literature Review.

Osteocraniosplenic syndrome-hypomineralized skull with gracile long bones and splenic hypoplasia: a case report and literature review: We report herein an intrauterine growth-restricted preterm nwonate with a lethal bone dysplasia characterized by severe hypomineralization of the skull, absent medullary lucency flared metaphyses fishbone-like diaphysis and overtubulated long vones. Dysmorphic features included flat facies, bulging forehead, vevus flammeus, depressed nasas bridge, short philtrum, inverted U-shape mouth, mild micrometic dwarfism, and brachydactyly. The infant's lungs and spleen were hypoplastic. The findings are compatible with the 19 previously reported cases that used different terminology: osteocraniostenosis, gracile bone disorders and osteocraniosplenic syndrome. We present the clinical, pathological and cytogenetic findings of this rare disorder.