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Immunodeficiencies in Adults: Key Considerations for Diagnosis and Management.

Immunodeficiencies in adults are increasingly recognized yet often remain underdiagnosed, leading to significant morbidity from recurrent infections, autoimmunity, and malignancy. Both primary immunodeficiencies (PIDs), now known as inborn errors of immunity (IEI), and secondary immunodeficiencies (SIDs) contribute to immune dysfunction in adults. Although SIDs are more common in adults due to factors like medications, malignancies, metabolic disorders, chronic conditions, and protein-losing conditions, IEI-particularly common variable immunodeficiency (CVID)-can also manifest in adulthood wit

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… Influenza and Covid-19 - Pneumococcal PCV20 - Recombinant zoster vaccine from age 18 - Tetanus, Diphtheria, Pertussis (Tdap) if not up to date Transplantation [ 88 , 89 ] | Solid Organ Transplantation - Annual Influenza and Covid-19 - Pneumococcal PCV20 pretransplant and a booster after transplant - Poliovirus … up to date Hematopoietic Stem Cell Transplant Recipients - Annual Influenza and Covid-19 - Pneumococcal: 3 doses of PCV20, starting 3 months post-transplantation - Haemophilus influenza serotype b: 3 doses 6–12 months after transplantation - Hepatitis B: 3 doses 6–12 months after transplantation - Poliovirus …

A bicistronic retrovirus vector containing a picornavirus internal ribosome entry site allows for correction of X-linked CGD by selection for MDR1 expression.

Chronic granulomatous disease (CGD) is an inherited hematologic disorder involving failure of phagocytic cell oxidase to produce superoxide (O2-.), resulting in recurrent infections. The success of retrovirus gene therapy for hematopoietic diseases will be limited both by the efficiency of ex vivo transduction of target cells and by the ability of corrected cells to replace uncorrected cells in vivo. Using MFG-based retrovirus vectors containing oxidase genes, we have previously demonstrated in vitro correction of CGD, but transduction rates were low. In the present study we explore a strategy

Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial.

Measles virus (MV) vaccine strains have shown significant preclinical antitumor activity against glioblastoma (GBM), the most lethal glioma histology. In this first in human trial (NCT00390299), a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA), was administered in recurrent GBM patients either at the resection cavity (Group A), or, intratumorally on day 1, followed by a second dose administered in the resection cavity after tumor resection on day 5 (Group B). A total of 22 patients received study treatment, 9 in Group A and 13 in Group B. Primary endpoint was s

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… This hypothesis is corroborated by clinical observations with several other viruses including Delta-24-RGD 32 , poliovirus 33 , and Toca-511 34 where response rates ranging from 9–13% were observed. … Desjardins A Recurrent glioblastoma treated with recombinant poliovirus New Engl. J. Med. 2018 379 150 161 10.1056/NEJMoa1716435 29943666 PMC6065102 34. Cloughesy TF Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma Sci. Transl. …

Нейромиелит Оптика Спектрум С односторонним ретробулбаром Неритом: доклад по делу.

Нейромиелитное расстройство спектра (NMOSD) включает в себя аутоиммунное генезис, проявляющееся в атаках оптического неврата (ON) и поперечного миелита (TM), а также экспрессивное аквапорина 4 (NMO-IgG) или миелин олиго-эндокитного гликотеина (MOGAb). В редких случаях болезнь может также иметь клиническое представление только с ТМ без ТМ и без ТМ. Эти условия также включены в спектр. Мы представляем случай 50-летнего пациента с жалобами на размытое зрение в левом глазу, боль в шее и онемение рук за несколько месяцев до госпитализации.После консультации с офтальмологом была произведена магнитна

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… Infectious diseases This vast group of infectious diseases involves the CNS: viral myelitis, which can be caused by varicella-zoster virus, herpes simplex virus, HIV, HTLV 1/2, tick-borne encephalitis virus, enteroviruses, Epstein-Barr virus, cytomegalovirus, West Nile virus, and poliovirus, neurotuberculosis …

Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject

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… Revaccination with measles, tetanus, poliovirus, Haemophilus influenzae type B, meningococcus C, and pneumococcus vaccines in children after hematopoietic stem cell transplantation. Clin Infect Dis 2007; 44(5): 625–634. 115. Tomblyn M, Chiller T, Einsele H. et al. … Long-term immunity to poliovirus after vaccination of allogeneic stem cell transplant recipients. Bone Marrow Transplant 2004; 34(12): 1067–1069. 118. Engelhard D, Handsher R, Naparstek E. et al. Immune response to polio vaccination in bone marrow transplant recipients. …

"Catch-Up Vaccinations Post-Stem Cell Transplant: A case series and review of the literature".

Stem cell transplantation (SCT), including autologous and allogeneic approaches, is a potentially curative therapy for various hematologic malignancies and selected non-malignant disorders. Autologous stem cell transplantation (ASCT) is an established curative treatment for hematologic malignancies, including Hodgkin lymphoma (HL). Non-Hodgkin Lymphoma (NHL), and Multiple Myeloma (MM), but infectious complications remain a major challenge. Vaccination is an essential strategy to reduce the risk of vaccine-preventable infections following transplant. This case series describes immunocompromised

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… According to the CDC and the Advisory Committee on Immunization Practices (ACIP), antibody titers to vaccine‑preventable diseases—including tetanus, poliovirus, measles, mumps, rubella, and encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae type b—can decline significantly …

Vaccine Allergy? Skin Testing and Challenge at a Tertiary Pediatric Hospital in Melbourne, Australia.

BACKGROUND: The rate of true vaccine allergy is unknown. Children with potential IgE-mediated adverse events following immunization (AEFI) should undergo allergy investigation that may include skin testing or challenge. Previous protocols tend to be highly conservative and often suggest invasive testing for all, a practice not evidence based, technically difficult, and unpleasant in children. It has more recently been suggested that skin testing may be restricted to those with allergic-like events within the first hour and those with a history of anaphylaxis. OBJECTIVE: We aimed to describe t

Mesenchymal-Stem-Cell-Based Therapy against Gliomas.

Glioblastoma is the most aggressive, malignant, and lethal brain tumor of the central nervous system. Its poor prognosis lies in its inefficient response to currently available treatments that consist of surgical resection, radiotherapy, and chemotherapy. Recently, the use of mesenchymal stem cells (MSCs) as a possible kind of cell therapy against glioblastoma is gaining great interest due to their immunomodulatory properties, tumor tropism, and differentiation into other cell types. However, MSCs seem to present both antitumor and pro-tumor properties depending on the tissue from which they c

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… Herpes simplex virus-1 [ 61 , 62 , 63 ], adenovirus [ 64 ], reovirus [ 65 ], measles viruses [ 66 ], Newcastle disease viruses [ 67 ], and poliovirus [ 68 ] are a few of them. … Recurrent Glioblastoma Treated with Recombinant Poliovirus N. Engl. J. Med. 2018 379 150 161 10.1056/NEJMoa1716435 29943666 PMC6065102 69. Marelli G. Howells A. Lemoine N.R. Wang Y. Oncolytic Viral Therapy and the Immune System: A Double-Edged Sword Against Cancer Front. …

Вирусы и "Мозг-отношение к беде".

Неврологические расстройства, некоторые из которых связаны с вирусными инфекциями, растут из-за старения и увеличения численности населения. Несмотря на крепкую защиту центральной нервной системы, некоторые вирусы эволюционировали, чтобы пробить их, что часто приводит к ужасным последствиям. В этом обзоре мы рассказываем о различных способах проникновения различных вирусов в ЦНС и о последствиях таких вторжений. Последствия могут проявляться в виде острых заболеваний, таких, как энцефалит, менингит, или приводить к долгосрочным последствиям, таким, как нервно - мышечная дисфункция, как это име

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… Those human infecting viral pathogens that take the former route include rabies virus (RABV), poliovirus (PV), and alpha herpesviruses. … Some prophylactic vaccines have been extraordinarily efficacious, most notable those against polioviruses, but few viral neuropathogens are currently controllable with vaccines. …

What is new in the pathogenesis and treatment of IgA glomerulonephritis.

Recently, new findings have been clarified concerning both pathogenesis and treatment of IgA nephritis. The four hits theory has been confirmed but several genetic wide association studies have allowed finding several genes connected with the pathogenesis of the disease. All these new genes apply to each of the four hits. Additionally, new discoveries concerning the microbiota and its connection with immune system and IgA generation have allowed finding out the role of the mucosa in IgA nephropathy pathogenesis. The IgA treatment is also changed included the future possibilities. The treatment

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… Several other pathogens, such as Helicobacter pylori and poliovirus, affect the production of IgA1 and the hypogalactosylation process[ 29 , 30 ]. According to another hypothesis, the occurrence of tonsillitis is believed to be related to IgAN. … Saccharomyces boulardii prevents oral-poliovirus vaccine-induced IgA nephropathy in mice. Pediatr Nephrol. 2008;23:1287–1291. doi: 10.1007/s00467-008-0813-2. 31. …

Vaccine schedule recommendations and updates for patients with hematologic malignancy post-hematopoietic cell transplant or CAR T-cell therapy.

Revaccination after receipt of a hematopoietic cell transplant (HCT) or cellular therapies is a pillar of patient supportive care, with the potential to reduce morbidity and mortality linked to vaccine-preventable infections. This review synthesizes national, international, and expert consensus vaccination schedules post-HCT and presents evidence regarding the efficacy of newer vaccine formulations for pneumococcus, recombinant zoster vaccine, and coronavirus disease 2019 in patients with hematological malignancy. Revaccination post-cellular therapies are less well defined. This review highlig

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… recombinant zoster virus vaccine; COVID‐19, coronavirus disease 2019; DGHO, German Society of Hematology and Oncology; DT, full dose diphtheria vaccine; DTaP, higher dose diphtheria, tetanus, and acellular pertussis vaccine; DTPa‐IPV, higher dose diphtheria, tetanus, acellular pertussis, and inactivated poliovirus … combination vaccine; dTpa‐IPV, reduced antigen formulation diphtheria–tetanus–pertussis–inactivated poliovirus combination vaccine; ECIL‐7, European Conference on Infections in Leukaemia; GvHD, graft‐versus‐host disease; HBV vaccine, hepatitis B virus; Hib, Haemophilus influenzae type B conjugate vaccine …

Immunization coverage levels among 19- to 35-month-old children in 4 diverse, medically underserved areas of the United States.

BACKGROUND: The National Immunization Survey demonstrates that national immunization coverage in 2002 remained near the all-time highs achie … , defined as receipt of 4 doses of diphtheria and tetanus toxoids and pertussis vaccine, 3 doses of poliovirus vaccine, 1 dose of measles, mumps, and rubella vaccine, 3 doses of Haemophilus influenzae type B vaccine, and 3 doses of hepatitis B vaccine (the 4:3:1:3:3 series). ANALYSIS: We examined the association between coverage level and independent variab …

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

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… Herpes Simplex Virus (oHSV) and adenoviruses (oAds) and (2) replication-deficient viral vectors used as vehicles for other therapeutic genes e.g. polioviruses. Most ongoing clinical trials in glioblastoma are using oHSVs ( Table 3 , Figure 3B ) ( 193 – 197 ). … PVSRIPO is a type 1 (Sabin) live-attenuated poliovirus vaccine that carries a heterologous internal ribosomal entry site (IRES) of human rhinovirus type 2 (HRV2) ( 200 ). …

Infectious complications after CAR T-cell therapy: mechanisms, risk stratification, and prevention.

Chimeric antigen receptor (CAR) T-cell therapy is an established treatment for relapsed or refractory B-cell malignancies. Despite therapeutic success, infectious complications remain a major contributor to non-relapsed morbidity and mortality. The risk of infection reflects a prolonged and multifactorial state of immunosuppression resulting from lymphodepleting chemotherapy, treatment-related cytopenia, sustained CD4+ T-cell lymphopenia, B-cell aplasia with hypogammaglobulinemia, and the use of corticosteroids or cytokine-directed therapies for the management of immune effector cell-associate

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… herpes simplex virus, VZV varicella-zoster virus, PJP Pneumocystis jirovecii pneumonia, TMP-SMX trimethoprim–sulfamethoxazole, CMV cytomegalovirus, CAR T chimeric antigen receptor T-cell, DTaP/Tdap diphtheria-tetanus-acellular pertussis vaccine, Hib Haemophilus influenzae type b vaccine, IPV inactivated poliovirus … herpes simplex virus, VZV varicella-zoster virus, PJP Pneumocystis jirovecii pneumonia, TMP-SMX trimethoprim–sulfamethoxazole, CMV cytomegalovirus, CAR T chimeric antigen receptor T-cell, DTaP/Tdap diphtheria-tetanus-acellular pertussis vaccine, Hib Haemophilus influenzae type b vaccine, IPV inactivated poliovirus …

Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments.

Glioblastoma (GBM) tumors are the most aggressive primary brain tumors in adults that, despite maximum treatment, carry a dismal prognosis. GBM tumors exhibit tissue hypoxia, which promotes tumor aggressiveness and maintenance of glioma stem cells and creates an overall immunosuppressive landscape. This article reviews how hypoxic conditions overlap with inflammatory responses, favoring the proliferation of immunosuppressive cells and inhibiting cytotoxic T cell development. Immunotherapies, including vaccines, immune checkpoint inhibitors, and CAR-T cell therapy, represent promising avenues f

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… OVs utilizing modified herpes simplex virus, adenovirus, measles virus, parvovirus, reovirus, and poliovirus, amongst others, are being studied in clinical trials against GBM worldwide ( 93 ). … Key examples include HSV-1, adenovirus, reovirus, measles virus, Newcastle disease virus, and poliovirus ( 112 ). To circumvent the limitations imposed by the BBB, innovative delivery methods such as convection-enhanced delivery (CED) have been utilized. …

Targeting autoimmune mechanisms by precision medicine in Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Cur

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… Poliovirus-infected macrophages, and latently and litycally Epstein–Barr virus (EBV)-infected B cells and plasma cells, were detected in MG but not in normal control thymuses ( 32 , 33 ), supporting the hypothesis that IFN-β over-expression and chronic inflammation might be triggered by persistent viruses … Detection of poliovirus-infected macrophages in thymus of patients with myasthenia gravis . Neurology . ( 2010 ) 74 : 1118–26 . doi: 10.1212/WNL.0b013e3181d7d884 20368632 33 Cavalcante P Serafini B Rosicarelli B Lorenzo M Barberis M Antozzi A . …

Malignant pleural mesothelioma.

Malignant pleural mesothelioma remains a difficult tumor to treat, much less cure. Currently, the best chance for long-term survival lies with early diagnosis and aggressive surgical extirpation, but given the typically long delay between the onset of symptoms and diagnosis, this is only possible with a high index of suspicion and an aggressive diagnosis workup. Early referral to a tertiary center experienced in the treatment of MPM may be important for several reasons: (1) decreased risk of tumor spread along multiple thoracenesis/biopsy tracts, (2) the availability of specialized pathologic

Mortality in patients with alpha-mannosidosis: a review of patients' data and the literature.

BACKGROUND: Alpha-mannosidosis is a rare autosomal recessive lysosomal storage disorder (LSD) caused by reduced activity of alpha-mannosidase. Clinical manifestations include skeletal dysmorphism, mental impairment, hearing loss and recurrent infections. The severe type of the disease leads to early childhood death, while patients with milder forms can live into adulthood. There are no mortality studies to date. This study aimed to investigate the age at death and the causes of death of patients with alpha-mannosidosis who had not received disease-modifying treatment. METHODS: Clinicians and

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… There is evidence for immunodeficiency in alpha-mannosidosis patients, with children with alpha-mannosidosis who had been vaccinated against tetanus, diphtheria and poliovirus showing significantly lower levels of serum antibodies than the normal population [ 7 ], suggesting antibody levels in these …

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-fifth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difficulty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to

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… Some of these viruses are as follows: adenovirus [ 69 , 70 ], vaccinia virus [ 71 , 72 ], tanapoxvirus [ 73 ], parapoxvirus [ 74 ], marabavirus [ 75 ], poliovirus [ 76 ], measles virus [ 77 ], herpes simplex virus [ 78 ], and Newcastle disease virus [ 79 ]. 2.1. … Recombinant Poliovirus for Cancer Immunotherapy Annu. Rev. Med. 2018 69 289 299 10.1146/annurev-med-050715-104655 29414253 PMC6013836 77. Jing Y. Chavez V. Ban Y. Acquavella N. El-Ashry D. Pronin A. Chen X. Merchan J.R. …