Objective: To investigate the clinical characteristics of severe Mycoplasma pneumoniae pneumonia (SMPP) complicated by pleural effusion in children. Methods: A retrospective analysis was conducted on 993 hospitalized children diagnosed with SMPP who were admitted to the Department of Respiratory Medicine, Machang Branch of Tianjin Children's Hospital, from January to December 2023 and underuent bronchoscopy. Patients were divided into a pleural effusion group and a non-pleural effusion group according to the presence of pleural effusion. General characteristics, clinical manifestations, laboratory findings, imaging features, and treatment profiles were compared between the two groups. Statistical analyses were performed using the Mann-Whitney U test and the chi-square test. Results: Among the 993 children with SMPP, 487 were male and 506 were female; the age at presentation was 8.0 (6.0, 10.0) years; including 145 cases in the pleural effusion group and 848 cases in the non-pleural effusion group. Compared with the non-pleural effusion group, patients in the pleural effusion group had longer pre-admission fever duration, longer total fever duration, and longer hospital stays, as well as higher incidence of hypoxemia and atelectasis, levels of neutrophil-to-lymphocyte ratio, C-reactive protein, ferritin, procalcitonin, lactate dehydrogenase, D-dimer, interleukin-6, interleukin-10, and interferon-γ were higher, along with higher rates of glucocorticoid use and higher proportions of mucus plugs and longitudinal mucosal folds observed by bronchoscopy (all P<0.05). In contrast, the incidence of moist rales, lymphocyte counts, and the rate of radiologic improvement before discharge were lower in the pleural effusion group (all P<0.05). Conclusion: Among children with SMPP undergoing bronchoscopy, those with pleural effusion have a more pronounced inflammatory response, aprolonged disease course, impaired ventilation, and more prominent airway inflammatory manifestations, indicating a more complicated clinical course.

General Background: Coronavirus disease 2019 (COVID-19) is a multisystem infectious disease with diverse clinical manifestations and outcomes, particularly among hospitalized patients. Specific Background: Individuals with chronic diseases frequently experience more complicated clinical courses during COVID-19 infection, requiring detailed clinical and laboratory assessment to understand disease progression. Knowledge Gap: Despite numerous investigations, uncertainty remains regarding which clinical and laboratory characteristics are associated with severe and critical forms of COVID-19 in patients with multiple underlying conditions. Aims: This study analyzed the clinical manifestations and laboratory characteristics of COVID-19 patients with comorbid conditions and identified indicators associated with severe disease progression. Results: A total of 182 hospitalized patients with moderate, severe, and critical COVID-19 were examined during 2021–2022 using comprehensive clinical, laboratory, and instrumental assessments. The majority presented with severe disease (80.8%). Coronary heart disease, hypertension, anemia, type 2 diabetes mellitus, and obesity were the most frequent accompanying conditions. Severe and critical cases were more common among elderly individuals and those with multiple concurrent disorders. Clinical manifestations included fever, cough, dyspnea, and weakness, frequently accompanied by bilateral or polysegmental pneumonia and respiratory failure. Laboratory findings showed leukocytosis, neutrophilia, lymphopenia, elevated erythrocyte sedimentation rate, increased C-reactive protein levels, hyperglycemia, and altered liver and renal function markers, particularly in critically ill patients. Novelty: The study provides integrated clinical and laboratory characterization of hospitalized COVID-19 patients with multiple concurrent diseases. Implications: Identification of these clinical and laboratory indicators supports early risk stratification, timely initiation of intensive treatment, and improved management of patients with severe COVID-19. Highlights: Elderly Hospitalized Individuals Frequently Present Severe or Critical Disease Stages. Respiratory Failure and Bilateral Pneumonia Appear Commonly in Advanced Clinical Cases. Systemic Inflammation Markers and Metabolic Abnormalities Increase in Critically Ill Groups. Keywords: COVID-19, Comorbidities, Laboratory Parameters, Pneumonia, Respiratory Failure.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of peripheral T-cell lymphoma (PTCL) and is frequently associated with autoimmune phenomena. Clinically, AITL shows an aggressive disease course and poor prognosis with currently available treatment strategies. We here report the case of a 64-year-old female patient who was diagnosed with AITL and showed a complicated clinical course due to concurrent immune-mediated thrombotic thrombocytopenic purpura (iTTP). To our knowledge, the presented case highlights a previously unreported association of both conditions. Treatment, including chemotherapy and iTTP-directed treatments, resulted in rapid clinical improvement and sustained remission of both the AITL and the concurrent iTTP. In AITL, transformed T-follicular helper cells (TFHs) are particularly thought to mediate hypersecretion of cytokines and excessive autoantibody production. Immunological disturbances to large parts mediated through these transformed TFHs are thought to trigger autoimmune conditions, as seen with iTTP in this patient. At 36 months post-treatment, the patient remains in complete remission for both AITL and iTTP. This case highlights the complex immunopathological relationship between AITL and autoimmune disorders possibly impeding diagnosis and treatment in a timely manner.

The criteria for Brief Resolved Unexplained Events (BRUE) are used to stratify the risk in infants presenting with apneic episodes. However, these criteria often classify a high proportion of infants as higher risk. This study aimed to investigate the etiology of apneic episodes, particularly those compatible with BRUE, and to assess whether age ≤60 days is associated with serious underlying conditions. We conducted a retrospective study of infants aged <1 year who presented with apnea as the chief complaint or had an ICD-10 code P28.4 (Other apnea of newborn) recorded between 2014 and 2018 at Skåne Pediatric University Hospital. The cohort was divided into a BRUE subgroup, which was further stratified into lower- and higher-risk groups based on current BRUE criteria, and additionally stratified without considering age as a higher-risk factor. Infants with an ICD diagnosis related to respiratory tract infection (RTI) or clinical signs of RTI were categorized into a separate RTI sub-cohort. A total of 340 infants were included. No specific diagnosis was identified in 253 (74.4%) cases, while 63 (18.5%) were diagnosed with viral RTIs. There were 9 (2.6%) cases with serious conditions during the first encounter, all of whom appeared unwell or had alarming signs at presentation excluding them from a BRUE diagnosis. The BRUE sub-cohort included 188 infants, of whom 143 (76.1%) were classified as higher risk using current criteria. When age ≤60 days was excluded as a risk factor, only 45 (23.9%) were classified as higher risk. None of the infants with serious diagnoses were misclassified as lower risk under the modified criteria. The RTI sub-cohort included 158 infants, with 111 (70.3%) hospitalized; 90 of these (81.1%) were discharged within two days. Serious underlying conditions and complicated clinical courses were rare among well-appearing infants aged under 1 year, with apneic episodes. Age ≤60 days did not appear to be associated with serious diagnoses in the BRUE sub-cohort. Well-appearing infants with RTI symptoms also had benign outcomes. These findings suggest that age may warrant re-evaluation as a risk factor in BRUE stratification, and that well-appearing infants with RTI symptoms may be appropriately classified as low risk.

Malignant peripheral nerve sheath tumor (MPNST) is a rare, high-grade soft tissue sarcoma that poses substantial diagnostic challenges. This tumor poses significant diagnostic challenges due to variable histologic patterns, limited neural marker expression, and overlap with the spectrum of other high-grade sarcomas. Its heterogeneous histologic patterns, limited expression of neural markers, and significant morphologic overlap with other high-grade sarcomas often complicate accurate identification. Diagnosis is challenging and often requires contributions from clinical findings, radiology, immunohistochemistry, and molecular diagnostics, necessitating a multidisciplinary team for diagnosis and management. MPNST is associated with a high rate of recurrence and metastasis; therefore, early detection and lifelong follow-up after treatment are essential. Here, we report a 39-year-old woman who was diagnosed with extraskeletal myxoid Chondrosarcoma (EMC) after excision of a left thigh mass. Two years afterward, she had locally extensive recurrence and FDG-avid mediastinal metastases. Advancing quality-assessment, comprising extensive histopathology and focused molecular investigations, reclassified the diagnosis as high-grade MPNST, based on CDKN2A deletion and the absence of NR4A32 rearrangement. This clarification changed the management, referring her to neoadjuvant chemotherapy, debulking surgery, and a subsequent plan of adjuvant therapy. This revised diagnosis prompted a change in therapeutic strategy, with initiation of neoadjuvant chemotherapy followed by surgical debulking and planned adjuvant therapy. Although she had an initial response, the patient developed widespread metastatic disease and died 8 months later. This case highlights the difficulties in diagnosing MPNST, the importance of interdisciplinary teamwork, and the need for close monitoring in patients with high-grade MPNST.

Gastrointestinal Stromal Tumors (GISTs), derivatives of the Interstitial cells of Cajal, are the most common mesenchymal tumors of the gastrointestinal tract. Extra-gastrointestinal stromal tumors (EGISTs) are a subtype of GIST that represent less than 5% of all GISTs. EGIST arises either in the mesentery, omentum, or in the retroperitoneum, regardless of the gastrointestinal wall. Similar to GISTs, EGISTs are typically associated with mutations that result in gain of function in the KIT or PDGFRA receptor tyrosine kinase genes. Most EGISTs are found in the omentum and mesentery, and since they grow large in the abdominal cavity, most of them are large and palpable tumors. They are histologically defined as spindle or epithelioid cells, which are usually positive for CD117 (KIT) and DOG1. EGISTs are rare mesenchymal neoplasms that pose a significant clinical challenge due to their potential for aggression and a tendency to recur. We report a case of a high-risk, large mesenteric EGIST that had exhibited a complicated clinical course. The case went through an intraoperative tumor rupture, adjuvant treatment with imatinib, recurrence, and progression with increasing dose and second-line sunitinib treatment. EGISTs are more likely to have an aggressive clinical course and recurrence than GISTs of the same size and mitotic rate; therefore, aggressive treatment and long-term follow-up are needed. This case illustrates the impact of unfavorable prognostic factors, particularly tumor rupture and R1 resection, on the long-term prognosis of high-risk EGIST. It highlights the need for aggressive, multidisciplinary management, extended adjuvant therapy, and the challenges associated with managing sequential resistance in advanced EGIST treatment.

Necrotizing otitis externa (NOE) is arare, potentially life-threatening invasive infection of the external auditory canal that predominantly affects elderly and immunocompromised individuals-particularly those with diabetes mellitus. The disease may progress to skull base osteomyelitis and can lead to severe complications such as cranial nerve palsy, meningitis, or dural sinus thrombosis. The most common causative pathogen is Pseudomonas aeruginosa, although invasive fungal infections are increasingly recognized. The primary therapeutic strategy involves extended administration of pathogen-specific systemic antimicrobial agents. Surgical intervention may be required for complicated clinical courses. For monitoring disease progression and evaluating the therapeutic response, fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) in combination with computed tomography (CT) or magnetic resonance imaging (MRI) of the temporal bone has proven valuable. Lifelong closeknit otolaryngological follow-up is essential to detect recurrences early.

The critical events that trigger sepsis progression into life-threatening septic shock remain unclear. In agreement with reports that link a drop in platelet count to a complicated clinical course in sepsis patients, here we report that, during sepsis, mouse platelets become activated, deposit systemically on vascular walls, and stimulate perivascular mast cells (MC) by releasing platelet activating factor (PAF). In mouse models and patient samples, MC activation correlates with the development of shock in sepsis and is mechanistically linked to shock by inducing systemic hypotension, vascular leakage and microvascular perfusion abnormalities. Preventing platelet or MC activation, or inhibiting the activity of the major MC granule constituent chymase, averts progression from sepsis to shock and reduces mortality of septic mice. Thus, our work establishes that, during sepsis progression, platelet microvascular adhesion leads to MC-mediated vascular changes to culminate in septic shock and septic shock-associated mortality.

Abstract Introduction/Objective Spontaneous pneumothorax is a relatively rare presentation in otherwise healthy, pregnant or postpartum women, and it can mask other conditions. LAM is a relatively rare neoplastic disease which predominantly involves pulmonary and lymphatic systems in this group. It is often underdiagnosed until more advanced presentations, such as pneumothorax or chylous effusions. Concomitantly, dedifferentiated endometrial carcinoma is an uncommon yet aggressive gynecologic cancer, and it typically manifests with nonspecific symptoms. We describe a patient with spontaneous bilateral pneumothoraces with presenting feature of both pulmonary and nodal LAM in a female also with previously undiagnosed dedifferentiated endometrial adenocarcinoma. This case demonstrates the importance of pathology in the accurate discrimination between overlapping disease entities, accentuating the difficulty in diagnosing combined rare neoplasms. The aim of this article is to point out this diagnostic dilemma and to stress the necessity of keeping LAM in mind in female patients presenting with nonspecific pulmonary symptoms, especially in the presence of coexisting neoplasm that influences on the overall clinical presentation. This case underscores the need for histopathologic and immunohistochemical markers and the importance of multi-disciplinary approach in the management of complicated presentations. Methods/Case Report A 46-year-old nulligravid woman had acute dyspnea and a hemoglobin level of 2.6 g/dL. Chest X-ray showed bilateral pneumothoraces with subsequent emergent chest tubes. Pelvic imaging demonstrated thickened endometrium and bilateral adnexal masses, and retroperitoneal lympadenopathy. She had cis-video-assisted thoracoscopic surgery (VATS) on both the sides with wedge resection and pleurodesis. Histopathological sections of lung revealed nodular and cystic growth of spindle cells invading pulmonary parenchyma that were immunoreactive for HMB-45 and smooth muscle actin and consistent with pulmonary LAM. There were no features of tuberous sclerosis complex (TSC) favouring sporadic LAM. Other gynecologic surgery performed was hysterectomy, bilateral salpingo-oophorectomy and omentectomy and lymph node dissection. Pathology showed dedifferentiated endometrial adenocarcinoma with rhabdoid features with predominant involvement of ovaries and the omentum. Significantly, one external iliac lymph node had features of nodal LAM—spindle cell morphology and HMB-45 positivity—but no evidence for metastatic carcinoma. This uncommon dual pathology led to diagnostic dilemma. Given the histomorphologic and immunophenotypic overlap, a comprehensive immunohistochemical work up was a requisite to prevent misdiagnosis of LAM as metastatic disease. Definitive diagnosis was made by the cooperation with pathology, thoracic surgeon, gynecologic oncologist, and a pulmonologist departmentally. This case illustrates the diagnostic challenges of both rare diseases Results NA Conclusion This case illustrates an unusual association of pulmonary and nodal lymphangioleiomyomatosis and dedifferentiated endometrial carcinoma, which first presented with spontaneous bilateral pneumothoraces. The finding of LAM in the lung and lymph nodes in the setting of an aggressive gynecologic malignancy emphasizes the need for meticulous morphologic and immunohistochemical evaluation. HMB-45 staining differentiated nodal LAM from metastatic carcinoma. In the absence of thorough pathologic examination, nodal LAM can be mistaken for lymphatic metastasis from endometrial carcinoma, resulting in misdiagnosis and unnecessary treatment. This case highlights the importance of clinical suspicion and interdisciplinary communication when confronted with diagnostically difficult presentations. Our patient’s complicated clinical course illustrates the importance of considering rare diseases, such as LAM, as differential diagnoses of spontaneous pneumothorax, especially in women of childbearing age. Furthermore, concurrent occurrence of two hormonally responsive neoplasms in the breast triggers interesting queries relative to common molecular or environmental etiological factors. In the end, this case is a timely reminder of the central role of pathology in negotiating diagnostic uncertainty and in directing appropriate clinical care. Continued recognition and reporting of rare co-morbidites will contribute towards accruing the necessary knowledge base in order to refine diagnosis and patient management in such multifactorial presentations.

Background: Electromyography and nerve conduction studies (EMG-NCS) often yield nonspecific findings during the early stage of Guillain-Barré syndrome (GBS). Although useful for diagnosis, EMG-NCS are traditionally of little value in predicting a complicated clinical course, which is critical for timely decisions to initiate immunomodulatory treatment. We aimed to identify the early clinical and electrophysiologic predictors of respiratory failure, a prolonged hospital stay, and moderate-to-severe disability at discharge in GBS.Methods: We retrospectively analyzed the clinical and electrophysiologic data of adult GBS patients who were hospitalized during the early course of the disease (&lt;2 weeks from symptom onset).Results: Eighty-one patients aged 47.5 ± 16.1 years were analyzed. The most common clinical variants were Miller-Fisher syndrome (30.9%) and classic sensorimotor GBS (25.9%). The clinical variant was not predictive of a complicated clinical course. Instead, specific clinical features such as dysautonomia (p = 0.006) and marked motor deficits (p = 0.002) were predictive of the primary composite outcome of respiratory failure and/or a prolonged hospital stay, with dysautonomia (p = 0.035) also predictive of moderate-to-severe disability at discharge. The most common abnormalities in EMG-NCS were bilateral absence of the H-reflex (86.4%) and F-wave abnormalities (44.4%). The presence of F-wave abnormalities was predictive of both respiratory failure (p = 0.032) and a prolonged hospital stay (p = 0.001).Conclusions: Early F-wave abnormalities in GBS may serve as an electrophysiologic predictor of a complicated clinical course, suggesting that EMG-NCS can provide prognostic information to guide treatment decisions during the early stage of the disease.

Neonatal Graves’ disease (GD) is rare and serious condition with a complicated clinicalcourse, its details of the clinical features have not been clarified. This study aimed toclarify the clinical course of neonatal GD cases requiring anti-thyroid treatment. Weretrospectively analyzed records from 12 neonates (7 males) diagnosed with GD from 2012 to2021. All neonates had maternal histories of GD, with significantly elevated TRAb levels(≥ 19 IU/L) observed during the second or third trimester of pregnancy. At birth, TRAblevels were elevated in all neonates (≥ 17.4 IU/L). Thiamazole (MMI) was given to 11neonates, with additional potassium iodide (KI) and/or β-blockers in 10 cases; onereceived only KI and a β-blocker. Notably, maternal TRAb levels during late pregnancy weresignificantly correlated with neonatal TRAb levels at birth (R2 = 0.8454, p =0.027), and neonatal TRAb levels at birth were significantly associated with the durationof MMI treatment (R2 = 0.750, p = 0.002). Secondary central hypothyroidism wasobserved in 33% of cases (4/12), with unmeasurably low TSH levels at birth (< 0.01μIU/mL) as a significant risk factor for its development (p < 0.03). These findingssuggest that maternal TRAb levels significantly influence neonatal TRAb levels at birth,and neonatal TRAb levels may predict the duration of anti-thyroidal treatment.

ObjectivesStroke is a severe complication in patients with left ventricular assist devices (LVAD), significantly affecting quality of life and potentially leading to death. This study aimed to illustrate the clinical features, outcomes, and risk factors associated with stroke in LVAD patients, with the goal of identifying potential treatment targets.MethodsIn a study of 249 consecutive patients who underwent LVAD implantation, detailed evaluations were conducted regarding clinical characteristics, perioperative management, cardiovascular risk factors, comorbidities, and brain imaging. The etiology, treatment, and outcomes were subsequently assessed in individuals who encountered a stroke.ResultsEighty-three cerebrovascular events (CVE) occurred in 54/249 patients during a median study period of 2.2 years (0.4–3.5) with 53 ischemic events and 22 intracranial hemorrhages (ICH). Early peri- or postoperatively CVE in context to the LVAD implantation were identified in 31 patients. Competing risks regression analysis revealed that postoperative dialysis was associated with higher risk for CVE, considering death as competing risk event (HR 3.617; 95%-CI: 1.78–7.35; p ≤ 0.001). Modified Rankin Scale at outpatient visit did not differ in early CVE [3 (IQR 2–5) vs. 3 (IQR2–4), p = 0.146]. Late CVE frequently occurred during hospitalization for sepsis or in cardiac rehabilitation [n = 16/41 events (39%)]. Competing risk analysis treating death and heart transplantation as competitors identified history of stroke as associated factor [HR 3.564; 95%-CI (1.67–7.169); p = 0.001]. Mortality was not associated with CVE [with n = 27/54 (50%) vs. without CVE 94/195 (48.2%) p = 0.183].ConclusionPatients who require postoperative dialysis face a heightened risk for early cerebrovascular events (CVE) during and after LVAD implantation. Additionally, a history of stroke and complicated clinical courses should increase awareness regarding the potential for impending CVE in the long term.

BackgroundNeurolisteriosis, a central nervous system (CNS) infection caused by Listeria monocytogenes, is associated with significant morbidity and mortality, particularly in elderly and immunocompromised individuals. The objective of this study was to analyze the clinical and radiological data from the patients of this disease presenting to a tertiary care hospital. MethodsThis retrospective review analyzed clinical, laboratory, and neuroimaging data from 12 patients diagnosed with neurolisteriosis at Aga Khan University Hospital between September 2018 and March 2024. Diagnosis was confirmed through blood and/or cerebrospinal fluid cultures or polymerase chain reaction assays. Data was analyzed using Statistical Package for Social Sciences (version 25.0). ResultsThe median age was 68.5 years, with 58.3% being elderly (&gt;65 years) and 58.3% male. Most patients (91.7%) had underlying comorbidities, with diabetes mellitus and hypertension being the most common. Acute onset of symptoms was observed in two-thirds of cases. Fever (83.3%) and altered consciousness (75%) were the predominant presenting features. Meningeal enhancement was the most frequent neuroimaging finding (66.6%), followed by hydrocephalus (25%). The median time to radiological diagnosis (24 hours) was significantly shorter than to microbiological confirmation (72 hours). The mortality rate was 25%, with complicated clinical courses observed in 75% of patients. ConclusionNeurolisteriosis predominantly affects elderly and immunocompromised populations and presents with non-specific CNS infection symptoms. MRI plays a crucial role in early detection and management, given the delay in microbiological confirmation. Heightened clinical suspicion and prompt imaging can improve diagnosis and outcomes.

Risk Factors and Management of Cancer-Associated Thrombosis: The Ongoing Battle Between Efficacy and Safety of Anticoagulation.

Streptococcus pyogenes meningitis is a rare invasive disease, accounting for less than 2% of bacterial meningitis. We presented two case reports and conducted a systematic review using PUBMED, covering the database from its inception up to 31 December 2024, of pediatric cases of Streptococcus pyogenes meningitis. Only case reports and case series were included. Differences in clinical and laboratory parameters were compared between uneventful course and complicated admissions. A total of 57 cases were included. The median age at diagnosis was 4 years. A primary infection focus outside the brain was identified in 61.39% of cases. S. pyogenes was identified from cerebrospinal fluid in 66.66% of cases and from blood in 15.79%. Septic shock occurred in 24.56% of cases, and 36.84% had brain anatomical anomalies. All patients received broad-spectrum empiric antibiotics, while protein-synthesis inhibitors were administered in 26.31% of cases. A total of 17% of patients died, and 28.07% experienced sequelae. The identification of S. pyogenes from blood and a Phoenix Sepsis Score ≥ 2 were significantly associated with a complicated clinical course. Our findings may offer useful insights for the clinical management of Streptococcus pyogenes meningitis.

Abstract Lemierre's Syndrome is a rare, life-threatening condition with a prevalence of 3.6 cases per one million people. This condition presents as a complication of bacterial tonsillitis with a multitude of life-threatening complications, including septic shock, internal jugular vein thrombophlebitis, and invasion of the retropharyngeal space. Here we present a case of Lemierre's Syndrome complicated by extensive metastatic disease. Our patient was a 29-year-old male with no past medical history who presented with two days of worsening sore throat, fever, and shortness of breath after being recently diagnosed with tonsillitis at urgent care. He decompensated after arrival, requiring intubation for airway protection and vasopressors for septic shock. CT neck demonstrated complicated tonsillitis with left peritonsillar abscesses extending into the retropharyngeal space and mediastinum. CT chest demonstrated bilateral located pleural effusions. He underwent incision and drainage of the neck abscesses, and bilateral chest tubes were placed for the effusions. Cultures of the pleural fluid grew Streptococcus anginosus. The patient's clinical course was complicated by right internal jugular vein thrombophlebitis, an infected pericardial effusion, and a right-sided subsegmental pulmonary embolism. In addition, developing infarcts were demonstrated in his kidneys and spleen. He underwent urgent pericardial window in the setting of enlarging pericardial effusion with evidence of tamponade and bilateral video-assisted thoracoscopic surgery (VATs) with decortication due to persistent bilateral pleural effusions. The patient required a tracheostomy due to prolonged intubation in the setting of his complicated clinical course and was eventually discharged to a long-term care facility on oral antibiotics. Our case is an extremely rare example of disseminated Lemierre's Syndrome as a complication of bacterial tonsillitis. The incidence of Lemierre's in the general population is very low, most commonly presenting in the second or third decade of life in young, otherwise healthy individuals. The majority of cases are caused by Fusobacterium species; however, one third of patients will have an associated polymicrobial bacteremia. Our patient initially grew Streptococcus anginosus in his pleural fluid, which is an uncommon pathogen. Metastatic infection can present in over 60% of patients with internal jugular thrombophlebitis, with the most common sites of disseminated infection being the lungs, joints, liver, and, less frequently, the pericardium. This case demonstrated such infection of not only the lungs and heart, but also the spleen and kidneys. In conclusion, our case was unique due to the extent of dissemination and number of complications experienced by our patient despite appropriate diagnosis and management.

Clinical characteristics and short-term outcomes in patients with cardiogenic shock undergoing mechanical circulatory support escalation from intra-aortic balloon pump to impella: From the J-PVAD registry.

To the Editors: Primary immunodeficiencies (PIDs) are rare monogenic disorders. It is also uncommon for 2 PIDs to coexist. Here, we present the first case with dedicator of cytokinesis 8 (DOCK8) and complement factor I (CFI) deficiency diagnosed after necrotizing meningoencephalitis. A 45-day-old baby boy with Streptococcus agalactiae meningitis and status epilepticus was admitted to our pediatric intensive care unit. On admission, cranial magnetic resonance imaging was performed and revealed necrotizing meningoencephalitis and brain edema. On follow-up, his clinical status deteriorated due to increased intracranial pressure. An external ventricular drain was placed, and new cerebrospinal fluid sampling revealed both S. agalactiae and cytomegalovirus positivity. He also had cytomegalovirus viremia and urinary tract infection with Candida albicans. Because of his complicated clinical course, a pediatric immunology consultation was planned. Background history revealed that he was born to consanguineous parents at term, and his neonatal period was uncomplicated. An elder brother (patient 2) was newly under intravenous immunoglobulin treatment with suspicion of chronic mucocutaneous candidiasis. An immunologic workup was performed for either. While patient 1 had low IgG, IgM and C3 levels and a reversed CD4/CD8 ratio, patient 2 had low IgM and elevated IgE levels with normal serum complement levels. Patient 2 also had low CD3+ T cell, CD3+CD4+ T cell levels, lymphocyte proliferation responses and a reversed CD4/CD8 ratio compatible with combined immunodeficiency (Table 1). Exome sequencing was performed and identified a homozygous likely pathogenic variant [c.4507C>T (p. Gln1503*)] in the DOCK8 gene and a homozygous likely pathogenic variant [c.262C>T (p. Gln88*)] in the CFI gene in the patient 1. Patient 2 had the same variant of the DOCK8 gene but was a carrier for the CFI variant. Sanger sequencing confirmed the variants in both siblings. Unfortunately, we could not assess CFI levels. Antibacterial-antifungal prophylaxis and intravenous immunoglobulin treatments were started along with donor screening for hematopoietic stem cell transplantation. TABLE 1. - Immunologic Evaluation of Patients Patient 1 Age References Patient 2 Age References IgG, mg/dL 222 294–1165 1180 640–2010 IgA, mg/dL 36 13–72 225 44–244 IgM, mg/dL <16 33–154 <18 52–297 T.IgE, IU/L <17.5 5420 16.86 C3, g/L 0.54 0.9–1.8 1.23 0.9–1.8 C4, g/L 0.28 0.1–0.4 0.26 0.1–0.4 Absolute lymphocyte count, /mm3 3400 2450–8890 2900 1130–5520 Absolute eosinophil count, /mm3 390 0–400 510 0–400 CD3+T cells, % (/mm3) 762584 51–792400–8100 35 1015 55–791900–3600 CD3+CD4+ T cells, % (/mm3) 32 1088 31–541400–5200 13 377 26–49600–2000 CD3+CD8+ T cells, % (/mm3) 461564 10–31600–3000 24696 9–35300–1300 CD4+CD45RA+ T cells, % (/mm3) 26 884 25–451200–5600 10 290 20–41500–6600 CD19+ B cells, % (/mm3) 13 442 14–44500–3600 351015 11–31300–1200 CD3-CD16+CD56+ NK cells, % (/mm3) 5 170 5–23200–1800 16464 5–28200–1200 γδ cells, % 22 5 CD45RA+CD31+, % 60 >50 42 >50 CD4/CD8 ratio 0.69 0.54 Lymphocyte activation response to PHA, % CD3+CD25+ 84 52–94 33 43–97 CD3+CD69+ 84 45–85 32 45–100 Lymphocyte activation response to anti-CD3, % CD4+CD25+ 76 15 CD4+CD69+ 74 17 CD4+ 77 15 Bold values indicate abnormal laboratory levels.NK indicates natural killer cells; PHA, phytohemagglutinin. Infections, autoimmunity, allergies, malignancies and autoinflammatory diseases are clinical signs of PIDs. Despite diverse clinical spectrum, most patients present with infections, and the infection is the most common reason for referral to a clinical immunologist1 Biallelic loss of function variants in DOCK8 results in a combined immunodeficiency. DOCK8-deficient patients present with not only severe, recurrent and life-threatening sinopulmonary and mucocutaneous viral (molluscum contagiosum virus, herpes simplex virus and human papillomavirus), bacterial (Staphylococcus aureus) and fungal (C. albicans) infections but also severe eczemas/dermatitis, allergies and malignancies.2 To date, over 200 patients have been reported globally. The only curative treatment modality is hematopoietic stem cell transplantation. CFI negatively regulates alternative and classical complement pathways. CFI deficiency is a rare autosomal recessive disease leading to secondary reduction of C3 through consumption. To date, only 60 patients are reported to have complete factor I deficiency.3,4 Complete absence of factor I results in severe and recurrent infections (encephalitis, meningitis or bacteremia with Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis), glomerulonephritis, autoimmune disease and central nervous system inflammation.5 Specific vaccination or prophylactic antibiotics should be offered. Consanguinity may result in a high likelihood of concomitant immunodeficiencies, and clinicians should consider this situation. ACKNOWLEDGMENTS The authors thank the patient and his family for their support for this publication.

ABSTRACTBackgroundLeishmaniasis (LI) is a vector‐borne illness caused by a protozoan of the genus Leishmania. Data on the features of LI in patients with inflammatory bowel disease (IBD) are scarce.AimTo describe the characteristics of patients with IBD who present with leishmaniasis, infection outcomes and the risk factors associated with developing visceral leishmaniasis (VL).MethodsAn observational retrospective study performed in 26 hospitals in Spain, including all adult patients with IBD who developed Leishmaniasis from 2012 to 2022.ResultsA total of 73 patients were included [mean age 48 years; 65% male; 68% Crohn's disease]. Sixty patients (82.2%) presented localized cutaneous Leishmaniasis (CL), 2 (2.7%) diffuse CL, 3 (4.1%) mucocutaneous Leishmaniasis (MCL) and 8 (11%) VL. All patients were under biologicals (69 [94.5%]) or immunosuppressants (IMM) (4 [5.5%]) at Leishmaniasis diagnosis. AntiTNF was used in 97%, while 2 patients (3%) were receiving ustekinumab. Leishmaniasis resolution was achieved by 48% and 96% of the patients after 1 and 12 months, respectively. Biological withdrawal after Leishmaniasis diagnosis was not statistically related to increased rates of infection resolution among patients with localized CL. Age was the only risk factor associated with VL (OR 1.2, 95%CI 1.04–1.39; p = 0.012).ConclusionsLeishmaniasis in patients with IBD doesn't seem to follow a complicated clinical course, even in those with localized CL who do not discontinue biological therapy after infection diagnosis. Age might be a risk factor for developing VL. This infection should be considered for immunosuppressed patients with IBD and suggestive symptoms dwelling or travelling to endemic areas.

In the last decade, the share of obese adolescents in the European region has been steadily increasing, which is associated with a higher risk and earlier onset of a number of socially significant diseases with a complicated clinical course. Therefore, timely and rapid diagnosis of obesity in adolescents by applying cheap, convenient, non-invasive and reliable indirect methods such as anthropometric indices is crucial in health care settings. A systematic search and analysis of the available scientific literature was performed to identify relevant articles published over the period between January 2013 and December 2023 in Web of Science, Science Direct, Scopus, Research Gate and PubMed. Seventy full-text publications reporting the application of such anthropometric indices as Body Mass Index, Waist Circumference, Waist-to-Hip ratio and Waist-to-Height Ratio to identify the healthy risk of obesity among European adolescents were considered the most eligible and reviewed in detail. In order to generalize the results and obtain reliable statements, the method of meta-analyses (PRISMA) was applied. A systematic review covers seventy scientific studies involving 495,251 children and adolescents from twenty-six countries of the European continent. Body Mass Index (BMI) was established to be the leading, most commonly used anthropometric index to identify risk of obesity among adolescents in the European health setting and research. Waist Circumference (WC) and Waist-to-Height Ratio (WHtR) were the next popular indicators of obesity in European adolescents with increasing frequency of application in medical practice and population surveys. Surveys applying anthropometric measurements to determine obesity risk in children and adolescents turned out to be quite heterogenic in terms of sample characteristics, research methods and reported claims. Body Mass Index, Waist Circumference, Waist-to-Hip ratio and Waist-to-Height Ratio are simple indicators of obesity risk in European adolescents, but with greater practical advantages that determine their widespread use in medical and scientific settings. Until now, BMI has been the leading predictive indicator. In the last decade, the application of Waist Circumference and Waist-to-Height Ratio has grown significantly relying on the scientifically reported good discrimination capabilities. However, it is necessary to actualize and confirm universal international reference cutoff values of the considered anthropometric metrics determining the risk of obesity among European adolescents taking into account not only their age and sex but also stages of puberty and ethnicity, have yet to be actualized and confirmed.