Severe Infectious Complications Research Articles

Dissemination of non-typhoidal Salmonella during Plasmodium chabaudi infection affects anti-malarial immunity.

Malaria-associated bacteremia accounts for up to one-third of deaths from severe malaria, and non-typhoidal Salmonella (NTS) has been reported as a major complication of severe malarial infection. Patients who develop NTS bacteremia during Plasmodium infection show higher mortality rates than individuals with malaria alone. Systemic bacteremia can be caused by a wound or translocation from epithelial or endothelialsites. NTS is an intestinal pathogen, however the contribution of bacterial translocation from the intestinal tract during Plasmodium infection is not well studied. Here, we investigated the integrity of the intestinal barrier function of P. chabaudi-infected mice using large molecules and Salmonella infection. Intestinal histology and the adaptive immune response to malaria were also studied using light microscopy and flow cytometry. P. chabaudi infection compromised intestinal barrier function, which led to increased intestinal cellular infiltration. In addition, we observed increased serum lipopolysaccharide binding protein and leakage of soluble molecules from the intestine into the blood in infected mice. Plasmodium infection also increased intestinal translocation and dissemination of NTS to the liver. The adaptive immune response to P. chabaudi infection was also significantly impacted by NTS translocation. Reduced B and T cell activation were observed in co-infected animals, suggesting interference in the malaria-specific immune responses by bacteremia. These studies demonstrate that P. chabaudi infection induces failure of the barrier function of the intestinal wall and enhanced intestinal bacterial translocation, affecting anti-malarial immunity.

Incidence and severity of postoperative complications following neoadjuvant therapy and full-thickness local excision for moderately advanced rectal cancer.

e15167 Background: Trans-anal full-thickness local excision (LE) for patients with moderately advanced rectal cancer (MARC) whose tumors respond well to neoadjuvant therapy, is one approach for organ preservation. Some authors call for abandoning this procedure because it causes frequent and severe complications. We aim to report our post-operative complications rate and severity following this procedure. Methods: This is a retrospective review of the complications observed in 10 patients who underwent LE at our center between May 2017-January 2019. Primary outcomes were the presence and nature of complications associated with the treatment course. Results: Five patients were treated according to Phase II trial and received three months of FOLFOX chemotherapy followed by concurrent chemo-RT. Five additional patients received only concurrent chemo-radiotherapy as they were treated off protocol. Radiation therapy (RT) dose ranged between 45-54 Gy and the interval between completion of RT and LE ranged between 6-15 weeks; median 11.5 weeks. Gross residual disease was resected with no margin in nine patients. The size of removed specimens ranged between 6.8-1.4cm; median 2.2 cm with a depth of resection of 1.5-0.4 cm; median .6 cm. Two patients had a very low residual gross abnormality and the surgical resection extended to the dentate line. Both patients experienced grade III complications of severe pain, infection and fistula formation. Of the remaining 8 patients with tumors located between 3-8 cm from the anal verge, two patients developed grade II complications requiring a short course of antibiotics and symptomatic treatment. In both cases, symptoms resolved within one week. Conclusions: Post-operative complications in this setting are not prohibitive if LE doesn’t extend to the dentate line and the resection is limited to only residual abnormality with no mucosal margin. A complete pathological response, confirmed by LE after neoadjuvant therapy provides valuable prognostic information and can influence the intensity and burden of future follow up. The risk of surgical complications is acceptable in view of these advantages. LE remains a viable option in pursuing organ preservation for MARC when complete remission is achieved by neoadjuvant therapy.

Invasive mold disease of the central nervous system in children and adolescents with cancer or undergoing hematopoietic stem cell transplantation: Analysis of 29 contemporary patients.

Invasive mold disease (IMD) is a severe infectious complication in immunocompromised patients. The outcome of central nervous system (CNS) IMD is poor, but contemporary data, in particular in the pediatric setting, are lacking. For this retrospective multicenter analysis, pediatric patients<18 years with proven or probable CNS IMD receiving chemotherapy or undergoing allogeneic HSCT were reported by the local investigator. CNS IMD had to be diagnosed between 2007 and 2016. Proven CNS IMD was defined as compatible CNS imaging or macroscopic autopsy findings in conjunction with a positive microscopic or microbiological result in the brain tissue or cerebrospinal fluid. Probable CNS IMD was defined as compatible CNS imaging findings in combination with proven or probable IMD at a site outside the CNS. A total of 29 patients (median age, 14 years; 14 allogeneic HSCT recipients) were diagnosed with proven (n=12) or probable (n=17) CNS IMD. Aspergillus spp. was the most common fungal pathogen. All but one patient had IMD sites outside the CNS and eight patients (27.6%) were neurologically asymptomatic at diagnosis of CNS IMD. Forty-nine percent of the patients survived CNS IMD; however, 46.7% of the survivors suffered from severe long-term neurological sequelae. Our data suggest that (1) outcome of CNS IMD has improved in children as compared with previous series, (2) half of surviving patients suffer from severe neurological sequelae, and (3) imaging of the CNS should be performed in all children with IMD irrespective of neurological symptoms.

Selective culture of Escherichia coli to prevent infective complications of transrectal ultrasound-guided prostate biopsy: Clinical efficacy and analysis of characteristics of quinolone-resistant Escherichia coli.

To evaluate a regimen of targeted prophylaxis using rectal swab culture in patients undergoing transrectal ultrasound-guided prostate biopsy, and to investigate the characteristics of isolated fluoroquinolone-resistant Escherichia coli. A prospective study was carried out from June 2013 through December 2014. Rectal swabs were cultured on agar plates containing either 2μg/mL levofloxacin or 1μg/mL sitafloxacin before transrectal ultrasound-guided prostate biopsy. Patients with susceptible organisms received levofloxacin or sitafloxacin, whereas those with resistant organisms received directed antimicrobial prophylaxis according to the results of the antimicrobial susceptibility test. Patients with infectious complications after prostate biopsy were identified, and characteristics of patients carrying fluoroquinolone-resistant Escherichia coli were analyzed. A total of 397 men underwent transrectal ultrasound-guided prostate biopsy. Of these patients, 74 (18.6%) had fluoroquinolone-resistant Escherichia coli. All fluoroquinolone-resistant Escherichia coli were susceptible to amikacin and meropenem. The risk factor for possible fluoroquinolone-resistant Escherichia coli was age of ≥73years. Three (0.7%) patients who received appropriate antimicrobial prophylaxis had high-grade fever after the prostate biopsy. However, the pathogens were not fluoroquinolone-resistant Escherichia coli. Targeted antimicrobial prophylaxis in patients undergoing transrectal ultrasound-guided prostate biopsy can be associated with reducing severe infectious complications caused by fluoroquinolone-resistant Escherichia coli.

Cerebral Vascular Function in a Murine Model of Experimental Cerebral Malaria

Cerebral Malaria (CM) is among the most severe complications of malarial infection, with a mortality rate of 15–20%. Many survivors of CM develop lasting neurological sequalae, cognitive and behavioral impairments, or epilepsy. However, the etiology of CM is poorly defined, and treatment strategies are limited.Studies in the murine model of experimental cerebral malaria (ECM) have demonstrated cerebral blood flow (CBF) impairments that are associated with decreased nitric oxide (NO) bioavailability, blood brain barrier disruption, endothelial activation, impaired pial vessel reactivity, and cerebral ischemia. While these complications have been observed in vivo, cerebral artery function has not specifically been evaluated in ECM. Therefore, the aim of this study was to interrogate vasoreactivity and NO bioavailability in cerebral arteries (CAs) isolated from ECM mice, with the hypothesis that arterial vasodilatory function would be impaired by ECM.ECM was induced by Plasmodium berghei ANKA (PbA) infection in 10–12 week old C57Bl/6J mice and confirmed by murine coma score. On day 6 post‐infection, CBF was measured by laser speckle imaging. Cerebral arteries (CAs) were dissected from the brain into a modified Krebs buffer. Cerebral vasoreactivity was assessed by ex vivo pressure myography in middle cerebral arteries (MCA) obtained from control (n=4) and ECM (n=7) mice. NO production from dissected vessels was measured in an ex vivo Daf‐2 fluorescence assay (n=6, n=6).As expected, ECM mice had a significant, 25% reduction in CBF. However, ex vivo MCAs from ECM mice maintained robust endothelium‐dependent vasodilation to methacholine (MCh), which was inhibited by L‐NAME. ECM MCAs also exhibited normal dose responses to serotonin‐induced vasoconstriction and nitroprusside‐induced vasodilation, suggesting normal vasoreactivity of ECM cerebral arteries. Similarly, the results of the ex vivo Daf‐2 assay showed that the MCh‐induced NO production from ECM arteries was comparable to controls. To test whether ECM plasma would induce vascular dysfunction in ex vivo CAs, we incubated CAs obtained from ECM (n=2) and control (n=6) mice in plasma collected from ECM or control animals. Surprisingly, we found that plasma from ECM mice increased NO production of both ECM and control CAs.These unexpected results indicate that NO bioavailability and vasoreactivity are preserved in cerebral vessels in ECM, and that circulating factors in the plasma during PbA infection actively stimulate NO production. Our next focus will be on reconciling decreased CBF with preserved vascular function, as well as identifying the NO‐stimulating mediator(s) present within ECM plasma.Support or Funding InformationResearch and funding support from NIAID Division of Intramural Research.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Molecular Techniques Complement Culture-Based Assessment of Bacteria Composition in Mixed Biofilms of Urinary Tract Catheter-Related Samples.

Urinary or ureteral catheter insertion remains one of the most common urological procedures, yet is considered a predisposing factor for urinary tract infection. Diverse bacterial consortia adhere to foreign body surfaces and create various difficult to treat biofilm structures. We analyzed 347 urinary catheter- and stent-related samples, treated with sonication, using both routine culture and broad-range 16S rDNA PCR followed by Denaturing Gradient Gel Electrophoresis and Sanger sequencing (PCR-DGGE-S). In 29 selected samples, 16S rRNA amplicon Illumina sequencing was performed. The results of all methods were compared. In 338 positive samples, from which 86.1% were polybacterial, 1,295 representatives of 153 unique OTUs were detected. Gram-positive microbes were found in 46.5 and 59.1% of catheter- and stent-related samples, respectively. PCR-DGGE-S was shown as a feasible method with higher overall specificity (95 vs. 85%, p < 0.01) though lower sensitivity (50 vs. 69%, p < 0.01) in comparison to standard culture. Molecular methods considerably widened a spectrum of microbes detected in biofilms, including the very prevalent emerging opportunistic pathogen Actinotignum schaalii. Using massive parallel sequencing as a reference method in selected specimens, culture combined with PCR-DGGE was shown to be an efficient and reliable tool for determining the composition of urinary catheter-related biofilms. This might be applicable particularly to immunocompromised patients, in whom catheter-colonizing bacteria may lead to severe infectious complications. For the first time, broad-range molecular detection sensitivity and specificity were evaluated in this setting. This study extends the knowledge of biofilm consortia composition by analyzing large urinary catheter and stent sample sets using both molecular and culture techniques, including the widest dataset of catheter-related samples characterized by 16S rRNA amplicon Illumina sequencing.

Human cord blood-derived viral pathogens as the potential threats to the hematopoietic stem cell transplantation safety: A mini review.

Umbilical cord blood (UCB) is a valuable source of hematopoietic stem cells (HSCs) and potential alternative for bone marrow transplantation for patients who lack human leukocyte antigen (HLA)-matched donors. The main practical advantages of UCB over other HSC sources are the immediate availability, lower incidence of graft-versus-host disease, minimal risk to the donor, and lower requirement for HLA compatibility. However, the use of UCB is limited by delayed engraftment and poor immune reconstitution, leading to a high rate of infection-related mortality. Therefore, severe infectious complications, especially due to viral pathogens remain the leading cause of morbidity and mortality during the post-UCB transplantation (UCBT) period. In this context, careful screening and excluding the viral-contaminated UCB units might be an effective policy to reduce the rate of UCBT-related infection and mortality. Taken together, complete prevention of the transmission of donor-derived viral pathogens in stem cell transplantation is not possible. However, having the knowledge of the transmission route and prevalence of viruses will improve the safety of transplantation. To the best of our knowledge, there are few studies that focused on the risk of virus transmission through the UCB transplant compared to other HSC sources. This review summarizes the general aspects concerning the prevalence, characteristics, and risk factors of viral infections with a focus on the impact of viral pathogens on cord blood transplantation safety.

Infection-Induced Resistance to Experimental Cerebral Malaria Is Dependent Upon Secreted Antibody-Mediated Inhibition of Pathogenic CD8+ T Cell Responses.

Cerebral malaria (CM) is one of the most severe complications of Plasmodium falciparum infection. There is evidence that repeated parasite exposure promotes resistance against CM. However, the immunological basis of this infection-induced resistance remains poorly understood. Here, utilizing the Plasmodium berghei ANKA (PbA) model of experimental cerebral malaria (ECM), we show that three rounds of infection and drug-cure protects against the development of ECM during a subsequent fourth (4X) infection. Exposure-induced resistance was associated with specific suppression of CD8+ T cell activation and CTL-related pathways, which corresponded with the development of heterogeneous atypical B cell populations as well as the gradual infection-induced generation and maintenance of high levels of anti-parasite IgG. Mechanistically, transfer of high-titer anti-parasite IgG did not protect 1X infected mice against ECM and depletion of atypical and regulatory B cells during 4X infection failed to abrogate infection-induced resistance to ECM. However, IgMi mice that were unable to produce secreted antibody, or undergo class switching, during the repeated rounds of infection failed to develop resistance against ECM. The failure of infection-induced protection in IgMi mice was associated with impaired development of atypical B cell populations and the inability to suppress pathogenic CD8+ T cell responses. Our results, therefore, suggest the importance of anti-parasite antibody responses, gradually acquired, and maintained through repeated Plasmodium infections, for modulating the B cell compartment and eventually suppressing memory CD8+ T cell reactivation to establish infection-induced resistance to ECM.

The role of the maternity support worker in infection control in maternity care

Childbearing women and newborn babies are susceptible to infections. These can be a serious risk to their health and wellbeing, by altering the course of pregnancy, delaying recovery from childbirth, leading to longstanding morbidity or even causing death. Sepsis is a severe complication of infection that can rapidly lead to death of an infant or woman. Maternity support workers are well placed to recognise the signs of infection and help improve outcomes and prevent this serious complication.

SUCCESSFUL MANAGEMENT OF SACRAL POSTHERPETIC NEURALGIA WITH GANGLION IMPAR BLOCK - A CASE REPORT

Postherpetic neuralgia (PHN) is one of the most common and important complications of severe varicella-zoster infection, especially occurring in 20% of the elderly patients. A 59-year-old female presented with pain in the right sacral region for the past 3 months. The pain was preceded by herpes zoster. She was diagnosed as a case of Sacral PHN. We administered paramedian approach of ganglion impar block with 10 ml of 0.25% bupivacaine with 8 mg dexamethasone which resulted in immediate adequate pain relief. On follow-up after 8 weeks, the pain score continued to be less with 3/10. No complications were encountered. There was no sensory loss. We conclude that ganglion impar block with a combination of local anesthetic and steroid is a viable treatment option for sacral PHN.

Very Low Frequency Heart Rate Variability Predicts the Development of Post-Stroke Infections.

Stroke-induced immunodepression is a major risk factor for severe infectious complications in the immediate post-stroke period. We investigated the predictive value of heart rate variability (HRV) to identify patients at risk of post-stroke infection, systemic inflammatory response syndrome, or severe sepsis during the post-acute interval from days 3 to 5 after stroke onset. A prospective, observational monocentric cohort study was conducted in a university hospital stroke unit of patients with ischemic infarction in the territory of the middle cerebral artery without an ongoing infection at admission. Standard HRV indices were processed from Holter ECG. Recording started within the first day after the onset of stroke. Infection (primary endpoint: pneumonia, urinary tract, unknown localization) was assessed between days 3 and 5. The predictive value of HRV adjusted for clinical data was analyzed by logistic regression models and area under the receiver operating characteristic curve (AUC). From 287 eligible patients, data of 89 patients without event before completion of 24-h Holter ECG were appropriate for prediction of infection (34 events). HRV was significantly associated with incident infection even after adjusting for clinical covariates. Very low frequency (VLF) band power adjusted for both, the National Institutes of Health Stroke Scale (NIHSS) at admission and diabetespredicted infection with AUC = 0.80 (cross-validation AUC = 0.74). A model with clinical data (diabetes, NIHSS at admission, involvement of the insular cortex) performed similarly well (AUC = 0.78, cross-validation AUC = 0.71). Very lowfrequency HRV, an index of integrative autonomic-humoral control, predicts the development of infectious complications in the immediate post-stroke period. However, the additional predictive value of VLF band power over clinical risk factors such as stroke severity and insular involvement was marginal. The continuous HRV monitoring starting immediately after admission might probably increase the predictive performance of VLF band power. That needs to be clarified in further investigations.

Structural and Antiviral Studies of the Human Norovirus GII.4 Protease.

Norovirus is the leading cause of acute gastroenteritis worldwide with a yearly reported 700 million cases driving a $60 billion global socioeconomic burden. With no United States Food and Drug Administration approved therapeutics and the chance for severe chronic infection and life-threatening complications, researchers have identified the protease as a potential target. However, drug development has focused on the norovirus GI.1 strain despite its accounting for less than 5% of all outbreaks. Our lab aims to change focus for norovirus drug design from GI.1 to the highly infective GII.4, responsible for more than 50% of all outbreaks worldwide. With the first published crystal structure of the norovirus GII.4 protease, we have identified several significant differences in the structure and active site that have hindered development of a potent inhibitor targeting the norovirus GII.4 protease. With these new insights, we have begun designing compounds that demonstrate increased inhibition of the clinically most relevant norovirus GII.4 strain.

The diagnostic ability of procalcitonin to differentiate Gram-negative bacteria from Gram-positive bacteria and fungal bloodstream infections in critically ill patients

Bloodstream infection (BSI) is a severe infectious complication in critically ill patients. This study was aimed to investigate the diagnostic accuracy of procalcitonin (PCT) to differentiate Gram-negative bacteria (Gram-neg) from Gram-positive bacteria (Gram-pos) and fungal BSI. PCT and other inflammation markers of monomicrobial BSI patients were retrospectively collected and compared between patients with Gram-neg, Gram-pos, or fungal BSI. The differential diagnosis performance of PCT was evaluated by receiver operating characteristic curves (ROC). The area under curve (AUC) of PCT for differentiating Gram-neg BSI from Gram-pos BSI was 0.95 with an optimal cut-off value of 4.15 ng/mL, a sensitivity of 82.05%, and a specificity of 96.15%. AUC of PCT for differentiating Gram-neg BSI from fungal BSI was 0.92 with an optimal cut-off value of 3.13 ng/mL, a sensitivity of 84.62%, and a specificity of 88.89%. Serum PCT concentration can be used to differentiate Gram-neg from Gram-pos and fungal BSI.

Incidence of hospitalisation for severe complications of influenza virus infection in Japanese patients between 2012 and 2016: a cross-sectional study using routinely collected administrative data

ObjectiveTo calculate the incidence of hospitalisation due to acute respiratory failure, pneumonia, acute respiratory distress syndrome (ARDS), febrile seizures and encephalitis/encephalopathy among influenza-positive patients in Japan, where point-of-care tests are...

Alloanergization Method for Inducing Allospecific Hyporesponsiveness in PBMC Exposed to Allostimulation In Vitro in the Context of Costimulatory Molecule Blockade.

Alloantigen-specific hyporesponsiveness can be induced in alloreactive T cells contained within the whole peripheral blood mononuclear cell (PBMC) population by stimulating these responder cells ex vivo with HLA-mismatched stimulator PBMC as the antigen presenting cell (APC) source, in the presence of a CD28 costimulation blocking agent. As a result of this approach, specific alloreactivity is markedly decreased (by 1-2 logs), but third-party alloresponses and in vitro responses relying on the activation of pathogen- and tumor-associated antigen T-cell functional activities are not globally impinged upon (Guinan et al. N Engl J Med 340(22):1704-1714, 1999, Davies et al. Transplantation 86(6):854-864, 2008, Davies et al. Cell Transplant 21(9):2047-61, 2012). This method has been used clinically to alloanergize bone marrow and PBMC allografts, creating ex vivo cell therapies for adoptive transfer to blood cancer patients at high risk of disease relapse whose best option was to receive haploidentical hematopoietic cell transplants. These early phase trials consisting of, or containing, alloanergized T-cell infusions show promise in reducing graft-versus-host disease (GvHD), providing more rapid immune reconstitution, and decreasing severe post-transplant infectious complications and disease relapse. Herein, we describe this straightforward technique for generating alloanergized PBMC as it is performed in the research lab setting using belatacept for CD28-mediated costimulatory blockade (CSB) and PBMC isolated by Ficoll Hypaque gradient centrifugation as responders and APC. We also describe methods for evaluating subsequent alloproliferation to first and third party stimulation as well as assessment of cell division, pathogen-specific immunity, or allosuppression. The technique has successfully been transferred to collaborating labs, largely owing to the flexibility of using fresh or frozen PBMC, the lack of a requirement for specially isolated APC populations, and the ability to scale up or scale down the cell numbers that are to be anergized.

Chemotherapy-Free Combination of Obinutuzumab and Ibrutinib in First LINE Treatment of Follicular Lymphoma. the Alternative Study By the German Low Grade Lymphoma Study Group (GLSG)

Chemotherapy-Free Combination of Obinutuzumab and Ibrutinib in First LINE Treatment of Follicular Lymphoma. the Alternative Study By the German Low Grade Lymphoma Study Group (GLSG)

РОЗРОБКА СИСТЕМИ ЗНЕЗАРАЖЕННЯ УЛЬТРАЗВУКОВОГО ХІРУРГІЧНОГО ІНСТРУМЕНТУ

Prevalence of gunshot wounds in modern world is associated with criminalization of society, terrorist threats, increase of a number of local military conflicts and civil unrest. Search and devel-opment of methods for reducing blood loss, accelerating the healing of postoperative wounds and scars resorption is an important goal of modern surgery, the solution of which is facilitated by the use of ultrasound. The use of ultrasonic surgery in military medicine and the use of piezoelectric elements as the source of ultrasound are perspective.Primary surgical treatment of wounds is the main method of preventing the development of se-vere infectious complications of gunshot wounds. When using an ultrasonic surgical instrument, an urgent task is to disinfect it before and after the operation. The purpose of this work consists in the development of disinfection method for destruction of pathogen of infection on the cutting part of ultrasonic surgical instrument. In the paper a diagram is worked out and the design of tension transformer is conducted for ultraviolet emitters, the dock-station is constructed for a mobile ultrasonic surgical instrument for its loading and the process of desinfection. The model of ultrasonic surgical instrument and disinfection method for destruction of pathogen of infection on the cutting part of ultrasonic surgical instruments are developed. The worked out surgical instrument is mobile and autonomous, that is provided by the use of Li-ion accumulators, reliable and has considerable tenure of employment of active elements from piezoceramics, comfortable in exploitation and simple in a management due to the use of ergonomic handle.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma.

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma.

CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and progressive accumulation of mature B lymphocytes in the peripheral blood, lymphoid tissues, and bone marrow. CLL is characterized by profound immune defects leading to severe infectious complications. T cells are numerically, phenotypically, and functionally highly abnormal in CLL, with only limited ability to exert antitumor immune responses. Exhaustion of T cells has also been suggested to play an important role in antitumor responses. CLL-mediated T cell exhaustion is achieved by the aberrant expression of several inhibitory molecules on CLL cells and their microenvironment, prominently the programmed cell death ligand 1/programmed cell death 1 (PD-L1/PD-1) receptors. Previously, we showed that CD84, a member of the SLAM family of receptors, bridges between CLL cells and their microenvironment. In the current study, we followed CD84 regulation of T cell function. We showed that cell-cell interaction mediated through human and mouse CD84 upregulates PD-L1 expression on CLL cells and in their microenvironment and PD-1 expression on T cells. This resulted in suppression of T cell responses and activity in vitro and in vivo. Thus, our results demonstrate a role for CD84 in the regulation of immune checkpoints by leukemia cells and identify CD84 blockade as a therapeutic strategy to reverse tumor-induced immune suppression.

Association of Immunoglobulin Levels, Infectious Risk, and Mortality With Rituximab and Hypogammaglobulinemia

Rituximab is an anti-CD20 chimeric antibody used in a wide variety of clinical indications. There has not been widespread adoption of consistent immune monitoring before and after rituximab therapy. However, there is a subset of patients who develop prolonged, symptomatic hypogammaglobulinemia following rituximab, and monitoring before and after rituximab therapy could help to identify these patients and initiate measures to prevent excess morbidity and mortality. To determine the current levels of screening for hypogammaglobulinemia (specifically, low immunoglobulin G), infectious risks associated with hypogammaglobulinemia, and variables associated with an increased risk of mortality. A cohort study was conducted of 8633 patients receiving rituximab from January 1, 1997, to December 31, 2017, at a large, tertiary referral center (Partners HealthCare System). Rituximab administration. The primary outcome measures were immunoglobulin measurements, infectious complications, and mortality. Cox regression analysis was used to examine the results of infectious complications on survival, adjusted for age, sex, and indication for rituximab use. Of the 8633 patients who received rituximab in the large, academic, health care system, 4479 satisfied inclusion criteria, with a mean (SD) age of 59.8 (16.2) years; 2280 patients (50.9%) were women. Most patients (3824 [85.4%]) did not have immunoglobulin levels checked before rituximab therapy. Of those who had levels determined, hypogammaglobulinemia was noted in 313 (47.8%) patients before initiation of rituximab. Following rituximab administration, worsening hypogammaglobulinemia was noted. There was an increase in severe infections after rituximab use in the study cohort (from 17.2% to 21.7%; P < .001). In the survival analysis, increased mortality was associated with increasing age (hazard ratio [HR], 1.02; 95% CI, 1.01-1.02; P < .001), male sex (HR, 1.14; 95% CI, 1.02-1.28; P = .02), and severe infectious complications in the 6 months before (HR, 3.14; 95% CI, 2.77-3.55; P < .001) and after (HR, 4.97; 95% CI, 4.41-5.60; P < .001) the first rituximab infusion. A total of 201 patients (4.5%) received immunoglobulin replacement following rituximab, and among these patients, higher cumulative immunoglobulin replacement dose was associated with a reduced risk of serious infectious complications (HR, 0.98; 95% CI, 0.96-0.99; P = .002). Many patients are not being screened or properly identified as having hypogammaglobulinemia both before and after rituximab administration. Monitoring of immunoglobulin levels both before and after rituximab therapy may allow for earlier identification of risk for developing significant infection and identify patients who may benefit from immunoglobulin replacement, which may in turn help to avoid excess morbidity and mortality.