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Cryptococcal meningoencephalitis (CM) classically occurs in individuals with advanced HIV infection, solid organ transplants, or other immunocompromising conditions. We report a case of fatal CM in a 78-year-old woman with well-controlled HIV infection who had delayed diagnosis, persistently elevated intracranial pressure and pleocytosis of the cerebrospinal fluid. Initial suspicion for CM was low due to her relatively high CD4+ T cell counts, which likely contributed to greater inflammation.

Transfer of convalescent plasma (CP) had been proposed early during the SARS-CoV-2 pandemic as an accessible therapy, yet trial results worldwide have been mixed, potentially due to the heterogeneous nature of CP. Here we perform deep profiling of SARS-CoV-2-specific antibody titer, Fc-receptor binding, and Fc-mediated functional assays in CP units, as well as in plasma from hospitalized COVID-19 patients before and after CP administration. The profiling results show that, although all recipients exhibit expanded SARS-CoV-2-specific humoral immune responses, CP units contain more functional antibodies than recipient plasma. Meanwhile, CP functional profiles influence the evolution of recipient humoral immunity in conjuncture with the recipient’s pre-existing SARS-CoV2-specific antibody titers: CP-derived SARS-CoV-2 nucleocapsid-specific antibody functions are associated with muted humoral immune evolution in patients with high titer anti-spike IgG. Our data thus provide insights into the unexpected impact of CP-derived functional anti-spike and anti-nucleocapsid antibodies on the evolution of SARS-CoV-2-specific response following severe infection., Convalescent plasma (CP) has been trialed as a therapy for SARS-CoV-2 symptoms, but its heterogenous nature precludes uniform outcomes. Here the authors perform deep profiling of CP, as well as plasma of CP recipients before and after transfer, to find CP-mediated, spike/nucleocapsid-focused modulations of humoral responses in the recipient.

Background. Previous reports have described cases of abscess formation by Streptococcus constellatus involving the oral cavity, gastrointestinal tract, and septic thrombophlebitis of the right ovarian vein with subsequent bacteremia and septic shock. Ascending infection from the genital tract to the fallopian tubes resulting in peritonitis from Streptococcus constellatus is a rare clinical circumstance where there is minimal information in the literature to guide its diagnosis, management, and expected prognosis. Case. A 36-year-old G3P0111 developed a tubo-ovarian abscess two weeks after intrauterine device (IUD) removal and then rapidly decompensated with septic shock from peritonitis due to Streptococcus constellatus infection. The patient was also newly diagnosed with diabetes and in diabetic ketoacidosis (DKA) on presentation. She received broad-spectrum antibiotic coverage and required two exploratory surgical procedures to obtain source control. Two Interventional Radiology- (IR-) guided drainage procedures were subsequently performed to drain remaining fluid collections. Her recovery involved a prolonged ICU stay. On hospital day seventy-three, after receiving approximately 8 weeks of antibiotics and the above noted procedures the patient was discharged to a subacute rehabilitation facility. Conclusion. Streptococcus constellatus is a highly pathogenic organism once a systemic septic infection has become established that can cause an ascending genital tract infection resulting in tubo-ovarian abscess formation, peritonitis, and septic shock.

Cryptococcus neoformans causes life-threatening meningoencephalitis. Human immunodeficiency virus (HIV) infection is the most significant predisposing condition, but persons with other immunodeficiency states as well as phenotypically normal persons develop cryptococcosis. We retrospectively reviewed medical records of all patients with a diagnosis of cryptococcosis between 2005 and 2017 at our inner-city medical center in the Bronx, an epicenter of AIDS in New York City, and analyzed demographic data, clinical manifestations, laboratory findings, treatment, and mortality for these patients. In sum, 63% of the cases over this 12-year period occurred in HIV-infected patients. And 61% of the HIV-infected patients were non-adherent with antiretroviral therapy, 10% were newly diagnosed with AIDS, and 4% had unmasking cryptococcus-associated immune reconstitution inflammatory syndrome. The majority were Hispanic or black in ethnicity/race. HIV-uninfected patients (47/126) were older (P < .0001), and the majority had an immunocompromising condition. They were less likely to have a headache (P = .0004) or fever (P = .03), had prolonged time to diagnosis (P = .04), higher cerebrospinal fluid (CSF) glucose levels (P = .001), less CSF culture positivity (P = .03), and a higher 30-day mortality (P = .03). Cases in HIV-uninfected patients were often unsuspected during their initial evaluation, leading to a delay in infectious diseases consultation, which was associated with mortality (P = .03). Our study indicates that HIV infection remains the most important predisposing factor for cryptococcosis despite availability of antiretroviral therapy and highlights potential missed opportunities for earlier diagnosis and differences in clinical and prognostic factors between HIV-infected and HIV-uninfected patients.

In the absence of an effective vaccine or monoclonal therapeutic, transfer of convalescent plasma (CCP) was proposed early in the SARS-CoV-2 pandemic as an easily accessible therapy. However, despite the global excitement around this historically valuable therapeutic approach, results from CCP trials have been mixed and highly debated. Unlike other therapeutic interventions, CCP represents a heterogeneous drug. Each CCP unit is unique and collected from an individual recovered COVID-19 patient, making the interpretation of therapeutic benefit more complicated. While the prevailing view in the field would suggest that it is administration of neutralizing antibodies via CCP that centrally provides therapeutic benefit to newly infected COVID-19 patients, many hospitalized COVID-19 patients already possess neutralizing antibodies. Importantly, the therapeutic benefit of antibodies can extend far beyond their simple ability to bind and block infection, especially related to their ability to interact with the innate immune system. In our work we deeply profiled the SARS-CoV-2-specific Fc-response in CCP donors, along with the recipients prior to and after CCP transfer, revealing striking SARS-CoV-2 specific Fc-heterogeneity across CCP units and their recipients. However, CCP units possessed more functional antibodies than acute COVID-19 patients, that shaped the evolution of COVID-19 patient humoral profiles via distinct immunomodulatory effects that varied by pre-existing SARS-CoV-2 Spike (S)-specific IgG titers in the patients. Our analysis identified surprising influence of both S and Nucleocapsid (N) specific antibody functions not only in direct antiviral activity but also in anti-inflammatory effects. These findings offer insights for more comprehensive interpretation of correlates of immunity in ongoing large scale CCP trials and for the design of next generation therapeutic design.

BackgroundInitiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated.MethodsWe compared plasma levels of immunoglobulins, C. neoformans glucuronoxylomannan (GXM) capsule-specific and laminarin (Lam)-binding IgM and IgG, and percentages of peripheral blood total and memory B cells between 27 HIV-infected patients with CM who developed C-IRIS and 63 who did not, and evaluated associations of these parameters with risk of C-IRIS.ResultsPrior to initiation of ART, plasma IgM, Lam-binding IgM (Lam-IgM), Lam-IgG, and GXM-IgM levels were significantly lower in patients who developed C-IRIS than those who did not. Multivariate analysis revealed significant inverse associations between C-IRIS and IgM (P = .0003), Lam-IgM (P = .0005), Lam-IgG (P = .002), and GXM-IgM (P = .002) independent of age, sex, HIV viral load, CD4+ T-cell count, and cerebrospinal fluid fungal burden. There were no associations between C-IRIS and total or memory B cells.DiscussionAntibody profiles that include plasma IgM, Lam-IgM, Lam-IgG, and/or GXM-IgM may have value in furthering our understanding of C-IRIS pathogenesis and hold promise as candidate biomarkers of C-IRIS risk.

Electrocorticographic (ECoG) spectral patterns obtained during language tasks from 12 epilepsy patients (age: 12-44 years) were analysed in order to identify and characterize cortical language areas. ECoG from 63 subdural electrodes (500 Hz/channel) chronically implanted over frontal, parietal and temporal lobes were examined. Two language tasks were performed. During the first language task, patients listened to a series of 50 words preceded by warning tones, and were asked to repeat each word. During a second memory task, subjects heard the 50 words from the first task randomly mixed with 50 new words and were asked to repeat the word only if it was a new word. Increases in ECoG gamma power (70-100 Hz) were observed in response to hearing tones (primary auditory cortex), hearing words (posterior temporal and parietal cortex) and repeating words (lateral frontal and anterior parietal cortex). These findings were compared to direct electrical stimulation and separate analysis of ECoG gamma changes during spontaneous inter-personal conversations. The results indicate that high-frequency ECoG reliably differentiates cortical areas associated with receptive and expressive speech processes for individual patients. Compared to listening to words, greater frontal lobe and decreased temporal lobe gamma activity was observed while speaking. The data support the concept of distributed functionally specific language modules interacting to serve receptive and expressive speech, with frontal lobe 'corollary discharges' suppressing low-level receptive cortical language areas in the temporal lobe during speaking.

Combination therapy with inteferon-alpha and ribavirin is an approved therapy for patients with chronic hepatitis C. However, even with the use of pegylated interferon, response rates are still poor in many difficult-to-treat groups, especially with genotype 1 and high viral loads. Retreatment of these patients remains challenging. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups. Thymosin alpha 1 is a polypeptide with immunomodulatory properties that has been suggested to increase response rates in patients with chronic hepatitis C. Herein, we describe two cases of retreatment patients with chronic hepatitis C who have failed prior pegylated interferon and ribavirin therapy. They received triple combination therapies of thymosin alpha 1, pegylated interferon and ribavirin and achieved sustained virological responses. These cases support that thymosin-alpha 1 may increase the efficacy of pegylated interferon plus ribavirin in the treatment of non-responders to previous combination therapy.

Background/aims The aim of this study is to assess serum procalcitonin (PCT) for early prediction of severe acute pancreatitis compared with multiple scoring systems and biomarkers. Methods Forty-four patients with acute pancreatitis confirmed by radiological evidences, laboratory assessments, and clinical manifestation were prospectively enrolled. All blood samples and image studies were obtained within 24 hours of admission. Results Acute pancreatitis was graded as severe in 19 patients and mild in 25 patients according to the Atlanta criteria. Levels of serum PCT were significantly higher in severe acute pancreatitis (p=0.001). The accuracy of serum PCT as a predicting marker was 77.3%, which was similar to the acute physiology and chronic health examination (APACHE)-II score, worse than the Ranson score (93.2%) and better than the Balthazar CT index (65.9%). The most effective cut-off level of serum PCT was estimated at 1.77 ng/mL (AUC=0.797, 95% CI=0.658-0.935). In comparision to other simple biomarkers, serum PCT had more accurate value (77.3%) than C-reactive protein (68.2%), urea (75.0%) and lactic dehydrogenase (72.7%). Logistic regression analysis revealed that serum PCT has statistical significance in acute severe pancreatitis. Assessment of serum PCT levels and length of hospital stay by simple linear regression analysis revealed effective p-value with low R square level, which could make only possibilty for affection of serum PCT to admission duration (r2=0.127, p=0.021). Conclusions Serum PCT was a promising simple biomarker and had similar accuracy of APACHE-II scores as predicting severity of acute pancreatitis.

AIM: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma. METHODS: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4. RESULTS: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T stage (P = 0.053). Coexistent nuclear localization of DLL4 was related to poor survival (P = 0.002). CONCLUSION: Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.

Background/Aims: The purpose of this study is to elucidate the efficacy and safety of combined peginterferon and ribavirin therapy in Korean patients with chronic HCV infection. Methods: We retrospectively analyzed the clinical records of 84 patients. Thirty five patients with genotype 1 HCV infection were treated with peginterferon α-2a 180 μg/week and ribavirin 1,000-1,200 mg/day for 48 weeks, and 49 patients with genotype non-1 were treated with peginterferon α-2a 180 μg/week and ribavirin 800 mg/day for 24 weeks. Results: An early virologic response was seen in 87.0% of patients with genotype 1 HCV. An end of treatment response (ETR) was seen in 82.6% and 97.6% of patients with genotype 1 and genotype non-1, respectively. An overall sustained virologic response (SVR) was seen in 53 patients (82.8%) of the 64 patients: in 16 (69.6%) of 23 patients with genotype 1 and in 37 (90.2%) of 41 patients with genotype non-1. An end of treatment biochemical response was seen in 58 patients (90.6%) [genotype 1, 20 patients (87.0%); genotype non-1, 38 patients (92.7%)], and a sustained biochemical response was achieved in 49 patients (76.6%) [genotype 1, 14 patients (60.9%); genotype non-1, 35 patients (85.4%)]. Independent factors affecting an SVR were HCV genotype and the baseline HCV RNA level. Conclusions: This study shows that a combination therapy of peginterferon and ribavirin is highly effective for chronic HCV infection, producing a high SVR and ETR. (Korean J Hepatol 2008;14:36-45)

Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea 󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚󰠚 Side effects of rituximab are mild in most cases, but there have been a few cases of severe pulmonary toxicity reported in elderly patients. Here we report a case of interstitial pneumonitis following rituximab treatment in a young patient. A 35-year-old woman with diffuse large B-cell lymphoma was admitted complaining of dry cough and dyspnea without fever after the 3 treatments with rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Her chest CT with highresolution CT scanning confirmed the presence of bilateral diffuse ground-glass opacities. The analysis of arterial blood gases indicated hypoxemia. The pulmonary function testing showed a restrictive pattern. There were no other findings suggesting an infection. The findings were compatible with a rituximab-induced interstitial pneumonitis. After the patient was treated with prednisolone, the symptoms resolved. Cases with rituximab-induced interstitial pneumonitis develop principally in elderly patients. However, the condition also can occur in young patients. (Korean J Hematol 2007;42:423-427.) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Background and Objectives:Drug-eluting stents (DES) have been shown to substantially reduce both angiographic and clinical restenosis. Cypher (sirolimus-eluting stent, Cordis, Johnson and Johnson, Florida, USA) and Taxus (paclitaxel-eluting stent, Boston Scientific, Boston, USA) are the two most widely used DESs, and they both have distinct pharmacological properties and release kinetics. It has been not studied whether these two DESs show different angiographic outcomes when they are simultaneously implanted in the same patient. Subjects and Methods:We retrospectively analyzed the angiographic findings of the short-term follow-up in 34 patients (average age: 63 year old, 9 women) in whom both Cypher and Taxus stents were implanted at the same time for the treatment of obstructive coronary lesion. Results:There was no significant difference in the basal angiographic characteristics of the lesions that had two stents deployed in terms of the AHA/ACC classification, reference diameter, the percent diameter stenosis and minimal luminal diameter. The post-procedure results were similar between the two stents. At 6 months follow-up, the Cypher stent displayed significantly less in-stent lumen loss compared with the Taxus stent (0.16±0.04 mm vs 0.27±0.04 mm; respectively, p=0.040) and a smaller percent diameter stenosis (15.9±1.3% vs 19.9±2.2%, respectively, p=0.049). Conclusion:The Cypher stent showed significantly less luminal loss during short term follow-up compared with the Taxus stent when implanted in the same patient. This result suggests that in a given individual patient, the Cypher stent induces less neointimal proliferation than does the Taxus stent. (Korean Circulation J 2006;36:600-604)