Corrigendum: Case report: Initial treatment adjustments and complications in ovarian cancer patient with inborn error of immunity.

[This corrects the article DOI: 10.3389/fonc.2022.843741.].

Case Report: Initial Treatment Adjustments and Complications in Ovarian Cancer Patient With Inborn Error of Immunity.

Background: Patients with inborn errors of immunity (IEI) have increased risk of developing cancers secondary to impaired anti-tumor immunity. Treatment of patients with IEI and cancer is challenging as chemotherapy can exacerbate infectious susceptibility. However, the literature on optimal cancer treatment in the setting of IEI is sparse. Objectives: We present a patient with specific antibody deficiency with normal immunoglobins (SADNI), immune dysregulation (ID), and stage III ovarian carcinoma as an example of the need to modify conventional treatment in the context of malignancy, IEI, and ongoing infections. Methods: This is a retrospective chart review of the patient's clinical manifestations, laboratory evaluation and treatment course. Results: Our patient is a female with SADNI and ID diagnosed with stage III ovarian carcinoma at 60 years of age. Her ID accounted for antinuclear antibody positive (ANA+) mixed connective tissue diseases, polyarthralgia, autoimmune neutropenia, asthma, autoimmune thyroiditis, and Celiac disease. Due to the lack of precedent in the literature, her treatment was modified with continuous input from infectious disease, allergy/immunology and oncology specialist using a multidisciplinary approach.The patient completed debulking surgery and 6 cycles of chemotherapy. The dosing for immunoglobulin replacement therapy was increased for prophylaxis. Chemotherapy doses were lowered for all cycles preemptively for IEI. The therapy included carboplatin, paclitaxel, bevacizumab, and pegfilgrastim. The patient completed six-months of maintenance medication involving bevacizumab.Her treatment course was complicated by Mycobacterium avium-complex (MAC) infection, elevated bilirubin and liver enzymes attributed to excessive immunoglobulin replacement therapy, and urinary tract infection (UTI) and incontinence.Cancer genetic analysis revealed no targetable markers and primary immunodeficiency gene panel of 407 genes by Invitae was unrevealing. Lab tests revealed no evidence of Epstein-Barr Virus (EBV) infection. Post-chemotherapy imaging revealed no evidence of cancer for 1 year and 4 months, but the disease relapsed subsequently. The patient's lung scarring requires vigilance. Conclusions: Our patient with ovarian cancer and IEI required modified treatment and prevention of complications. In cases of IEI, optimal chemotherapy should be titrated to minimize immunosuppression yet treat cancer aggressively while decreasing the risk of infection with prophylactic antibiotics and prolonged post-treatment surveillance, including pulmonary evaluation.

Disseminated blastomycosis in a patient with polycythemia vera on ruxolitinib.

Ruxolitinib (RUX) is a kinase inhibitor used in the treatment of various medical conditions and its mechanism of action involves suppression of the immune system. While beneficial in treatment of polycythemia vera, myelofibrosis and other indications, it can also increase a patient's susceptibility to various infections, including bacterial, viral and fungal. We present a case of a patient being treated with RUX who presented with a disseminated fungal infection. This case emphasises the need for vigilance of endemic fungal infections in individuals who are on RUX therapy.

Recurrent disseminated Mycobacterium avium in a female patient from Thailand with anti-interferon-gamma autoantibodies: dilemma on treatment approach.

Anti-interferon-gamma (IFN-γ) autoantibodies has been recognised as an adult-onset immunodeficiency in the past decade in people who originate from Southeast Asia. These patients are susceptible to particular opportunistic infections, especially non-tuberculous mycobacteria (NTM). We present the case of a woman whom originally came from Thailand with disseminated Mycobacterium avium complex infection (pleural, pericardium, bloodstream and lung parenchymal involvement). Her infection continued to progress while receiving proper antibiotic treatment. Once high titre neutralising anti-IFN-γ autoantibodies were detected, rituximab was added as adjunctive treatment. The patient had remarkable clinical improvement against persistence of anti-IFN-γ autoantibodies. Although her lung disease has improved, the patient continues on triple therapy for NTM. The kinetics of anti-IFN-γ autoantibodies in the context of clinical progression, indication and length for rituximab and triple therapy is discussed in view of the current literature.

Immediate Transfer for Clot Extraction in a Young Woman With Leukemia and Asparaginase-Associated Acute Cerebral Vein Thrombosis.

We present the case of an 18-year-old woman with B-cell acute lymphoblastic leukemia (ALL) who developed hemorrhagic stroke and epilepsia partialis continua due to acute cerebral vein thrombosis (CVT). The patient had 10 risk factors for CVT (including use of asparaginase chemotherapy for the ALL) and also unfortunately had 4 biomarkers for poor prognosis for outcome post-CVT diagnosis. Immediate transfer to a Comprehensive Stroke Center allowed for hyperacute neurointerventional clot extraction with rapid restoration of the patency of the superior sagittal sinus. This resulted in an unexpectedly favorable neurological outcome and simultaneously allowed for early resumption of chemotherapy for ALL after only a 5-day hiatus. Our case highlights the importance of immediate transfer of highest risk patients with multiple biomarkers for poor prognosis to a Comprehensive Stroke Center with endovascular and neurosurgical capabilities and the possibility of overcoming the odds of a poor outcome with venous clot extraction if medical management fails. Neurological deterioration due to escalating intracranial pressure with impending herniation may occur rapidly, and treatment at such facilities can be life-saving.

Multi-organ involvement secondary to varicella zoster virus, herpes simplex virus and cytomegalovirus in an immunocompromised patient.

The use of immunosuppressing agents can act as a catalyst for viral reactivation, promoting systemic infection with organ involvement. Current literature remains sparse on this topic but does provide individual case reports involving single viruses. We present the case of an immunocompromised patient with skin lesions, pancreatitis, colitis and hepatitis. Work-up revealed varicella zoster virus, which likely put the patient at risk for multi-organ involvement, as well as clinical suspicion of other implicated viruses, specifically herpes simplex virus and cytomegalovirus. A high clinical index of suspicion along with biopsy guidance for viral involvement in immunocompromised patients is crucial for early diagnosis and treatment of these conditions.

Effects of early introduction of non-invasive positive pressure ventilation based on forced vital capacity rate of change: Variation across amyotrophic lateral sclerosis clinical phenotypes.

PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with high morbidity and mortality. We evaluated the ability of pulmonary function tests to predict disease progression by ALS clinical phenotypes, and the timing of the introduction of non-invasive positive pressure ventilation (NIPPV). MATERIALS AND METHODS: A cohort study was performed in all adult patients who fulfilled El Escorial criteria at a tertiary-care academic medical centre for veterans in the USA from 1 January 2010 to 31 December 2014. Eligible patients underwent sitting and supine forced vital capacity (FVC) and the FVC rate of change (RoC) per month was calculated. ALS Functional Rating Scale-Revised (ALSFRS-R) scores were collected. RESULTS: A total of 137 patients were included in our analysis. The average survival from ALS onset was 31.40 (±40.04) months. The general cohort median (IQR) RoC was -0.87 (-2.55 to 0.34)/-0.65 (-2.55 to 0.70) % per month (P = 0.81) of the sitting/supine FVC, respectively. However, mean monthly RoC varied among the ALS phenotypes, with higher variation among global ALS, where greater decline in RoC was noted. The average time from ALS onset to tracheostomy was 27.88 (±22.21) months. The average sitting/supine FVC RoC for subjects requiring tracheostomy was -2.86 (±3.77)/-3.63 (±3.75) at the time of tracheostomy, compared to -1.190 (±2.38)/-1.07 (±3.78) for those who did not require the procedure. Although NIPPV use did not result in statistically significant improvements in either the sitting or supine FVC %, it did slow the RoC decline of patients with global ALS phenotypes. CONCLUSIONS: Initiation of NIPPV based on decline in RoC rather than the absolute value of either sitting or supine FVC may result in early stabilisation of ALS patients' pulmonary deterioration for the global clinical phenotype, and thus may have the potential for prolonging survival until tracheostomy or death.

Successful use of subcutaneous ivermectin for the treatment of Strongyloides stercoralis hyperinfection in the setting of small bowel obstruction and paralytic ileus in the immunocompromised population.

Severe Strongyloides stercoralis, such as hyperinfection syndrome, carries a high mortality risk. Even with appropriate treatment, patients may experience infectious complications and failure of therapy. Currently, there are no Food and Drug Administration-approved parenteral therapies available for treatment in patients who develop gastrointestinal complications from hyperinfection, including small bowel obstruction. A veterinary form of ivermectin is available as a subcutaneous injection, although current literature in humans is limited. We report on the successful treatment of two surviving immunocompromised patients with S. stercoralis hyperinfection syndrome after prompt recognition and initiation of veterinary subcutaneous ivermectin therapy.

Immunogenicity study of abbreviated rabies preexposure vaccination schedules.

OBJECTIVE: To evaluate abbreviated preexposure rabies vaccination schedules that would reduce cost and shorten time required for completion. METHOD: A random prospective immunogenicity study, using a group of 96 volunteer preclinical veterinary students, primary school children, and hospital-based health care workers. They were divided into six groups and administered abbreviated schedules of preexposure tissue culture rabies vaccines. Neutralizing antibodies were determined on days 0 and 360, and following boosters on days 367 and 374. RESULTS: All subjects, including one group that received only 0.1 mL intradermally at two sites on one day, had detectable neutralizing antibody titers 1 year later and responded with an accelerated antibody response when given booster injections. CONCLUSION: It might be possible to develop a 1-week and even one clinic visit preexposure vaccine schedule that would provide at least 1 year of immune memory.

Retrospective: animal attacks and rabies exposures in Thai children.

Over 50% of animal bites and potential rabies exposures in Thailand are in children and they also have the more severe injuries due to inexperience, smaller size and less ability to fend off attacks. Potential rabies exposures and animal bites are common in Thailand. Majority of these are in children where the extent of the injuries is also much more severe. The bitten areas correlate to the age of the children and level of the bitten animal head. These are areas noted for a higher risk of infection with rabies virus and shorter incubation periods. The vast majority of bites are due to dogs (86%) of which 74.6% are stray or community-owned animals. The prevalence of dog bites shows no seasonal variation in adults but there are two peaks during school vacation period for children. Extensive educational efforts directed at the Thai public are responsible for the rapid presentation of victims for post-exposure treatment. The dramatic reduction of human rabies deaths in Thailand during the last decades was achieved largely by the provision of expensive WHO standard post-exposure treatment, utilizing modern tissue culture vaccines and immunoglobulins. Canine and feline rabies is nevertheless still endemic and not likely to be controlled or eliminated till sustainable humane methods of dog population control and comprehensive countrywide canine rabies vaccination become possible through government policy.

Adverse reactions to human rabies immune globulin manufactured by the Thai Red Cross Society.

Rabies Immunoglobulins (RIG) are an essential part of optimal management of rabies exposures [World Health Organization (WHO)]. They provide protection against the virus during the critical initial 7 days before adequate endogenous vaccine induced antibodies are formed. Even though Human Rabies Immune Globulin (HRIG) is the ideal product for post-exposure rabies treatment it, like most biological, can cause very rare adverse reactions. A retrospective review of a series of 8737 patients, who received HRIG at one institution, revealed that only 15 (0.183 %) reported transient mild adverse reactions.

Common dilemmas in managing rabies exposed subjects.

Health care staff managing rabies exposures in a canine endemic or epidemic environments are often faced with having to make treatment decisions where there are no firm guidelines from WHO or local public health authorities. We have made an attempt to identify several common events that presented to a busy animal bite clinic in a rabies endemic country. Leading experts in this field have been queried about their management opinions in such situtions. They have revealed little uniformity. It appears that there is still much controversy and lack of evidence-based approach from international authorities, and that more research and data collection is needed to resolve some of these issues and provide better guidelines in this field.

Medical residency training in the US: important considerations.

The United States attracts medical scholars from abroad. However, the previously open-armed welcome extended to medical residents in America no longer exists for a variety of reasons. A series of barriers based on high educational standards and a rigid system of testing scientific and clinical skills and communication abilities, now tend to eliminate many applicants. Added to this is that American medical colleges now produce a near adequate number of new graduates and that foreign trained residents are often relegated to less desirable programs. These may not provide the level of training expected by the applicant. Less attractive programs are also less likely to enhance the scholar's chances of gaining an academic career and professional recognition on returning home. Applicants for residencies in the US should now be aware that only the best are likely to gain entrance to highly desired posts and to quality fellowships after completing a residency in America. All of this should be weighed against the stress and high costs that are now entailed in obtaining postgraduate medical training in America. This study endeavors to summarize what a young doctor should know about the application process for an American residency position and what he might expect from it.

Rabies in a Thai child treated with the eight-site post-exposure regimen without rabies immune globulin.

We report the case of a 7-year-old Thai girl that was bitten by a dog. She received prompt wound care followed by eight-site intradermal post-exposure rabies schedule using purified chick embryo vaccine. Treatment followed WHO recommendations for desperate situations where no rabies immune globulin (RIG) is available. The patient died 15 days later with classical symptoms and signs of encephalitic rabies.