Novel STAT-3 gain-of-function variant with hypogammaglobulinemia and recurrent infection phenotype.

Signal transducer and activator of transcription 3 (STAT-3) gain-of-function (GOF) syndrome is an early-onset monogenic inborn error of immunity characterized by multi-organ autoimmune disorders, growth failure and lymphoproliferation. We describe that STAT-3 GOF syndrome may be presented with hypogammaglobulinemia and recurrent severe upper and lower respiratory tract infections. In addition, the patient had lymphoproliferation, short stature and interstitial lung disease. Chest computerized tomography examinations showed mild bronchiectasis with areas of non-fibrosing alveolar-interstitial disease and maldevelopment of bilateral first ribs. Using Sanger sequencing, we revealed a novel c.508G>C, p.D170H STAT-3 variant affecting the coiled coil domain of STAT-3. Functional studies confirmed that p.D170H was a GOF variant, as shown by increased phosphorylated STAT-3 (pSTAT-3) and STAT-3 transcriptional activity. Our observation suggests that STAT-3 GOF syndrome can manifest in early childhood with hypogammaglobulinemia and recurrent severe respiratory tract infections. We suggest that patients with lymphoproliferation, hypogammaglobulinemia and severe recurrent infections should be screened for STAT-3 variants, even if autoimmune manifestations are missing.

[Gefitinib treatment in lung cancer -- rebiopsy, retreatment, remission]. / Rebiopszia és ismételt gefitinibkezeléssel elért remisszió tüdorákban.

The authors present a case of a 81-year-old non-smoker woman who was diagnosed with extended, bilateral bronchial adenocarcinoma in 2008. Two years later the tumor showed marked progression. EGFR sensitizing mutation (exon 19 deletion) was detected and gefitinib treatment was started in March 2010. After 12 months of spectacular and complete remission and 8 months of slow progression docetaxel therapy was applied and yielded partial remission. When progression redeveloped rebiopsy was performed and revealed EGFR exon 19 deletion again. Gefitinib retreatment was introduced in February 2013 and resulted in partial remission with excellent clinical status. In March, 2014 the patient is still on gefitinib treatment without any signs or symptoms of lung cancer but with very slow radiological progression. The authors overview the most important theoretical and practical questions regarding rebiopsy and retreatment in lung cancer with EGFR-TKI therapy.

Effect of Sex, Age, and Cardiovascular Risk Factors on Aortoiliac Segment Geometry.

Background: To investigate the geometry of the aortoiliac (AI) segment and its correlation with sex, age, and cardiovascular (CV) risk factors. Methods: Abdominal and pelvic CTA/MRA scans of 204 subjects (120 males; median age: 53 [IQR, 27-75] years) without AI steno-occlusive disease or scoliosis were retrospectively analyzed. The participants were enrolled consecutively, ensuring the representation of each age decade. An in-house written software was developed to assess AI elongation using the tortuosity index (TI) and absolute average curvature (AAC). Aortic bifurcation angle, common iliac artery (CIA) take-off and planarity angles, bifurcation asymmetry, and deviation from optimal bifurcation were calculated and evaluated. Demographic data, CV risk factors, and medical history were collected from electronic health records. Results: The elongation of the iliac arteries was more pronounced in males (TI: left CIA, p = 0.011; left EIA, p < 0.001; right CIA, p = 0.023; right EIA, p < 0.001; AAC: left EIA, p < 0.001; right EIA, p = 0.001). Age significantly influenced TI and AAC in all AI segments (all p < 0.001), but was also positively associated with the aortic bifurcation angle (p < 0.001), both CIA planarities (left, p < 0.001; right, p = 0.002), aortic bifurcation asymmetry (p = 0.001), and radius discrepancy (p < 0.001). Significant positive correlations were found between infrarenal aortic TI/AAC and chronic kidney disease (CKD) (p = 0.027 and p = 0.016), AAC of both CIAs and hypertension (left, p = 0.027; right, p = 0.012), right CIA take-off angle and CKD (p = 0.031), and left CIA planarity and hyperlipidemia (p = 0.006). Conclusion: Sex, age, and CV risk factors have a significant effect on the geometry of the AI segment.

Epidemiology and patients' self-reported knowledge of implantable medical devices: Results of a cross-sectional survey in Hungary.

BACKGROUND: Implantable medical devices (IMDs) are medical instruments embedded inside the body. Well-informed and empowered patients living with IMDs are key players of improving IMD-related patient safety and health outcomes. However, little is known about IMD patients' epidemiology, characteristics, and current awareness levels. Our primary aim was to investigate the point and lifetime prevalence of patients living with IMDs. Patients' IMD-related knowledge and determinants of IMDs' impact on their life were also explored. METHODS: An online cross-sectional survey was conducted. Respondents' IMD history, whether they received instructions for use and IMD's overall impact on life were recorded by self-reports. Patients' knowledge about living with IMDs was assessed on visual analogue scales (VAS, 0-10). Shared decision-making was analyzed by the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Descriptive statistics and subgroup comparisons between IMD wearers were performed for statistical differences. Significant determinants of IMD's overall impact on life were examined in linear regression analysis. RESULTS: In the total sample (N = 1400, mean age 58.1 ±11.1; female 53.7%), nearly one third of respondents were living with IMD (30.9%; 433/1400). Among them, the most frequent IMDs were tooth implants (30.9%) and intraocular lens (26.8%). Mean knowledge VAS scores were similar (range: 5.5 ±3.8-6.5 ±3.2) but differences by IMD types were observed. Patients who received instructions for use or reported better impact on life indicated higher self-reported knowledge. Regression confirmed that patients' knowledge was significant predictor of IMD's impact on life, but this effect was overwritten by the SDM-Q-9. CONCLUSIONS: This first comprehensive epidemiological study on IMDs provides basic data for public health strategy planning alongside the implementation of MDR. Improved self-perceived outcomes were associated with higher knowledge hence education of patients receiving IMD deserves consideration. We suggest to investigate further the role of shared decision-making on IMD's overall impact on patients' life in future prospective studies.

COVID-19-Related Intestinal Ischemia in A 7-Year Old Boy.

Severe abdominal pain and vomiting are common symptoms in children with pediatric multisystem inflammatory syndrome (PIMS). Mesenteric lymphadenitis and aseptic peritonitis are predominantly reported in cases where acute surgical abdomen was suspected and laparotomy was performed at the early stage of the pandemic. These reports generally discouraged surgeons to perform exploration in COVID-19-related cases and medical management was prioritized. Only a few COVID-19-specific surgical cases with intestinal ischemia were published. Here, we report another case of COVID-19-related intestinal ischemia complicated with Meckel's diverticulitis in a non-immunocompromised child who clearly required surgical intervention. In our case, the combination of COVID-19-related vasculitis and low blood pressure episodes may have contributed to this severe outcome.

The potentials and importance of imaging in large-vessel vasculitis / A nagyérvasculitisek képalkotó vizsgálatának lehetoségei és azok jelentosége

According to the nomenclature of the Chapel Hill Consensus Conference, giant-cell arteritis and Takayasu's arteritis belong to the group of large-vessel vasculitis. Recognition of these diseases is primarily based on the clinical assessment and the use of various vascular imaging modalities. With regard to the latter one, significant technological advances have been observed in recent years, which allow not only to make a diagnosis but also to evaluate the extent of the disease and the degree of vascular inflammation. In addition, subsequent complications of vascular inflammation can be examined. Ultrasound, computed tomography, magnetic resonance imaging, and positron-emission tomography represent imaging modalities that are essential for recognizing affected patients and planning effective treatment and follow-up. The review of this topic may be of interest to a number of medical specialties that are potentially involved in the care of these patients. Orv Hetil. 2020; 161(23): 939-950.

Aortic root reconstruction in a nine-year-old child: a case report.

Aortic root dilatation is present by the age of five years in approximately 35% of patients suffering from Marfan syndrome. However, children rarely undergo surgery for aortic aneurysm and aortic regurgitation during their first decade of life. A nine-year-old boy, who presented with severe aortic regurgitation associated with a 76.8 mm aneurysm of the ascending aorta, underwent a Bentall procedure. Since the aortic annulus was markedly dilated and the cusps were structurally abnormal, the aortic valve was not spared.

[The role of imaging methods in the pre- and intra-operative evaluation, and in post-operative follow-up of living donors in liver transplantation in Hungary]. / A képalkotó módszerek szerepe az élô donoros májtranszplantáció donorjelöltjeinek pre- és intraoperatív vizsgálatában, valamint posztoperatív követésében Magyarországon.

The evaluation protocol for liver donors can vary from centre to centre, but the main points are the same. Medical history, physical examination, common laboratory tests and psychosocial evaluation are followed by imaging, and specific haemostasis and viral serology tests. The first imaging examinations have the aim of excluding any disease; conventional chest radiography and abdominal ultrasound are performed. Liver volume, fat content, and vascular and biliary anatomy are then evaluated with contrast-enhanced, multiphase, multidetector row CT/CTA and MR cholangiography. Ultrasound guided liver biopsy, and in some cases digital subtraction angiography, should also be performed. During the first phase of the donor operation, intraoperative investigations are done: cholangiography for the final evaluation of the biliary tree and ultrasound of the hepatic and portal venous system to help draw the resection plane. Donors have regular imaging examinations in the early postoperative period for early detection of complications: mainly US or CT to check the remnant hepatic vascularisation and fluid collections in the operated area, or X-ray for thoracic disorders. It is recommended that regular checkups are performed in the late postoperative period. The paper describes the imaging protocol for donor evaluation applied at our institute at the beginning of our living related liver transplantation programme.

[Intracardiac echocardiography-guided cardiac tumor mass biopsy]. / Intracardialis echokardiográfia-vezérelt cardialis tumormassza-biopszia.

Primary cardiac tumors are rare and often occur without major symptoms. The appropriate therapy for cardiac tumors without metastasis is surgical resection and chemotherapy. However, for certain patients, when the tumor cannot be safely removed, biopsy is recommended since it allows histology examination and further therapeutical considerations. The aim of our case presentation is to describe the case of a 56-year-old woman, in whom cardiac tumor-mass was revealed because of recurrent pericardial fluids. The mass appeared to be non-resectable, therefore biopsy with an eventual histological examination was planned. Intracardiac echocardiography guided percutaneous biopsy was performed. Intracardiac ultrasound ensured accurate localization of the tumor, the catheter-based grasping device and the excision could be instantly monitored. This case demonstrates that an intracardiac ultrasound-guided tumor mass biopsy is a feasible method, which increases accuracy and ensures safety.

[The first case of human alveolar Echinococcosis in Hungary]. / A humán Echinococcus multilocularis infectio elso hazai esete.

Infection caused by Echinococcus multilocularis is a rare helminthiasis, human cases have not been diagnosed in Hungary until now. The endemic region is Central Europe; the occurrence of this infection has been reported from most of the neighbouring countries; however, E. multilocularis has been found in the red fox population in Hungary. Summarizing the recent knowledge concerning epidemiological, clinical patterns and therapeutic options, the authors describe the first Hungarian case of alveolar echinococcosis. In the presence of appropriate clinical findings, the possibility of this rare infection has to be considered in the differential diagnosis of infiltrative hepatic lesions.

[Pneumococcal meningitis in children--9 1/2-year-experience at Szent László Hospital, Budapest, Hungary]. / Pneumococcus-meningitis gyermekkorban--kilenc és fél év tapasztalata a Szent László kórházban.

BACKGROUND AND OBJECTIVE: No recent publications are available about pneumococcal meningitis in Hungarian children. The aim of this study was to collect data of epidemiological, clinical and prognostic features of pneumococcal meningitis in children treated at Szent László Hospital, Budapest, Hungary. METHODS: We conducted a retrospective review of medical charts and follow-up records of patients aged 1 to 18 years admitted to our Pediatric and Pediatric Intensive Care Units due to pneumococcal meningitis between 1st Jan 1998 and 30th Jun 2007. RESULTS: 31 children with 34 cases of pneumococcal meningitis were admitted to our hospital in the study period. Two children developed recurrent illness. The mean age was 6 years, 26% were under 1 year of age. The mean duration of hospital stay was 21 days, 97% required intensive care. Frequent clinical symptoms were fever (100%), nuchal rigidity and vomiting (78%), altered mental status (71%), Kernig's and Brudzinski's signs (58%) and seizures (41%). Otitis media, sinusitis, mastoiditis were present in 44%, 58%, 41%, respectively. Subdural effusion, parenchymal cerebral lesion and sinus thrombosis were documented in 5, 3 and 2 cases, respectively. One third of the patients received ceftriaxon, two thirds were administered ceftriaxon and vancomycin. Adjunctive therapy with dexamethasone was given to 91% of the children. 70% of patients required mechanical ventilation. 9 patients (25%) required endoscopic sinus surgery. In 13 cases (38%) mastoidectomy, in 5 children (15%) neurosurgery was performed. The case fatality rate was 23.5%. 8 (23.5%) patients had mild or moderate, 1 child (3%) developed severe neurological sequelae. CONCLUSION: Pneumococcal meningitis in children remains a source of substantial morbidity and mortality in childhood. The long hospital stay, the frequent need for intensive care and severe neurologic sequelae emphasize the importance of early diagnosis, early treatment and prevention with pneumococcal conjugate vaccines.

Multiple Myeloma of the Central Nervous System: 13 Cases and Review of the Literature.

Central nervous system involvement is a rare complication of multiple myeloma with extremely poor prognosis as it usually fails to respond to therapy. We present 13 cases diagnosed at two centers in Budapest and review the current literature. The majority of our cases presented with high-risk features initially; two had plasma cell leukemia. Repeated genetic tests showed clonal evolution in 3 cases. Treatments varied according to the era, and efficacy was poor as generally reported in the literature. Only one patient is currently alive, with 3-month follow-up, and the patient responded to daratumumab-based treatment. Recent case reports show promising effectivity of pomalidomide and marizomib.

[Imaging of pediatric brain tumors using somatostatin analogue 111Ih-DTPA-D-Phe1-octreotide]. / Gyermekkori agytumorok vizsgálata szomatosztatin-analóg (111In-DTPA-D-Phe1-octreotide) alkalmazásával.

Malignant solid tumors and leukemias are the second most common causes of death in childhood. The most frequent pediatric solid tumors are brain tumors. Brain tumors, especially medulloblastoma should be treated by surgery, irradiation and chemotherapy. However, chemotherapy has only moderate effect. Pediatric brain tumors, especially medulloblastomas, express somatostatin receptors. The aim of this study was the investigation of the expression of somatostatin receptors in pediatric brain tumors for diagnostic and therapeutic purpose. Fifty-six scintigraphic imagings (111In-DTPA-D-Phe1-octreotide) made in 45 children treated with brain tumor at the Unit of Oncology of the 2nd Department of Pediatrics, Semmelweis University. The diagnosis was medulloblastoma in 21 cases (46.7%). MRI scans have been performed parallel with the Octreoscan images. Octreoscan images were positive in 27 of 56 (48.2%) cases. The 27 positive Octreoscan images consisted of 16 medulloblastomas, 4 ependymomas, 4 astrocytomas and 3 glioblastomas. In 37 (66.1%) cases the results of Octreoscans were the same as those of the MRI scans. However, in 19 scans (33.9%) the outcome was different. Octreoscan imaging is not suitable for differential diagnosis in pediatric brain tumors, including medulloblastomas. Isotopes specifically binding to the somatostatin receptors (111In-DTPA-D-Phe1-octreotide) can be applied in medulloblastomas for diagnosis and follow-up treatment. In Octreoscan-positive tumors the Octreoscan images establish the opportunity to somatostatin analogue and/or specifically targeted radiation therapies.

Erdheim-Chester's disease of the heart: a diagnostic conundrum and collision with the same mass in the orbit.

Erdheim-Chester's disease is a rare multisystem xanthogranulomatosis, afflicting the skeletal system with the occasional involvement of soft tissues. We delineate an unusual case of a cardiac variant of Erdheim-Chester's disease presenting with pericardial effusion and as a collision with a synchronous orbital manifestation. We describe our diagnostic pathway and propose a novel treatment option involving nonsteroidal anti-inflammatory drugs. The role of cyclo-oxygenase in the disease process and inhibition thereof by NSAIDs is hypothesized and discussed.

Aortic coarctation reconstructed by resection and homograft replacement in the 1950s: long-term outcome 40 years after operation.

Since the first successful repair of aortic coarctation by Dr Clarence Crafoord in 1945, there are few data regarding late follow-up of homografts in this position. Between 1957 and 1959, 7 patients underwent surgical correction of aortic coarctation by Professor József Kudász at the Department of Cardiovascular Surgery, Semmelweis University, using freeze-dried aortic homograft. We were able to locate 4 of these patients and found no significant complications due to the operation. We report on this 40-year follow-up of implanted aortic homograft.

[Changes in calcium metabolism after parathyroidectomy in primary hyperparathyroidism]. / Primer hyperparathyreosis miatt végzett mútéteket követó kalciumanyagcsere-változások.

INTRODUCTION: Primary hyperparathyroidism causes elevated serum calcium level and osteopenia in most patients. AIMS: The authors measured the changes of calcium and bone mineral metabolism after parathyroidectomy in patients with primary hyperparathyroidism. PATIENTS: From 1995 to 2000, osteopenia was detected in 34 patients with primary hyperparathyroidism before surgery. There were 26 females (16 women were post-menopausal) and 8 males. The mean age of the patients was 54 years (range 19 to 64). The serum levels of calcium, phosphorus, alkaline phosphatase and the parathyroid hormone were measured before the operation and every year thereafter. Bone densitometry was performed at the lumbar spine (L II-IV) during the same period. RESULTS: The mean levels of calcium and parathyroid hormone rapidly decreased and varied in the normal range after the operation. The mean alkaline phosphatase concentrations also decreased after surgery, but in most cases the difference was not statistically significant. Bone densitometry showed increased bone mineral density at the lumbar spine (L II-IV) after the parathyroidectomy. One, 2, 3, 4 and 5 years after surgery the bone mineral density increased with 8.5%, 12.5%, 14.1%, 13.5% and 11.3% compared to the preoperative value respectively. The changes in bone mineral density values were not statistically significant 1 year after parathyroidectomy. The increase in the bone mineral density was significant two years after the operation. Nine patients had T-scores less than -2.5 before parathyroidectomy. CONCLUSION: The authors conclude, that the serum levels of calcium and parathyroid hormone significantly decreased after the parathyroidectomy in primary hyperparathyroidism. After successful surgical treatment the bone mineral density significantly increases and the osteopenia decreases or resolves.

[The role of ileostomy in the prevention and treatment of complications of deep rectal anastomoses]. / Az ileostoma értéke a mély rectum anastomosisok szövódményeinek megelózésében és kezelésében.

The authors analyzed their data of the last three and a half years about patients with temporary loop ileostomy. We formed 18 ileostomies in patients with rectum carcinoma where the anastomosis was performed in the mid or lower rectum. Ten ileostomies were formed because of anastomotic leak, eight to protect the anastomosis, although there were no signs of insufficiency at the time of the intraoperative testing. Sixteen of the 18 patients had no complications. There were two complications in connection with ileostomies, these stomas were closed earlier than usual. Two other patients needed permanent stomas. Fourteen ileostomies were reversed without complications after 6-8 weeks. Two patients with local septic complications, following the closure, were treated conservatively. No reoperations were needed because of anal incontinence or anastomotic stenosis. We consider loop ileostomy safe with low morbidity, it can prevent diffuse peritonitis and/or a permanent stoma. Its routine use is recommended in patients with "ultra low" anastomoses and in cases where the intraoperative air test is positive.