Maternal and fetal outcomes of pregnancy occurring after a diagnosis of immune-mediated thrombotic thrombocytopenic purpura.

Pregnancy is a well-established trigger for a first episode or relapse of immune thrombotic thrombocytopenic purpura (iTTP). Other outcomes of subsequent pregnancy after a diagnosis of iTTP are less well described. We conducted this retrospective cohort study to evaluate maternal and fetal outcomes of pregnancy in women with prior iTTP from the Johns Hopkins Thrombotic Microangiopathy Cohort. Of 168 women in the cohort, 102 were of reproductive age at diagnosis. Fourteen pregnancies (in 9 women) that occurred after the initial iTTP episode were included in the analysis. iTTP relapse occurred in 9 (64%) pregnancies. Out of the 9 instances of relapse, 5 relapses occurred in 2 women. Seven pregnancies (50%) ended in fetal death or miscarriage in the setting of iTTP relapse and three were electively terminated due to fear of relapse. Four pregnancies (50% of the 8 that progressed beyond 20 weeks) were complicated by preeclampsia or HELLP syndrome, which is over ten-fold higher than that of the general population. No maternal deaths occurred. Only 4 pregnancies resulted in live births, of which, 2 were pre-term. Pregnancy in women with prior iTTP is associated with a substantial risk of iTTP relapse and fetal loss. Preeclampsia and HELLP syndrome is also more common than that in the general population. ADAMTS13 monitoring and preemptive therapy may improve pregnancy outcomes, which needs to be evaluated prospectively.

Immunotherapy for Diffuse Large B-Cell Lymphoma: Current Landscape and Future Directions.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. B-cell receptor (BCR) pathway is essential for malignant B-cell growth, survival, and proliferation. Various immune cells, including T-cells and macrophages in the tumor microenvironment (TME) contribute to tumor cell survival and pathogenesis of chemo-resistance. The presence of many targets on the malignant B-cells and in the TME has led to emergence of novel therapeutic agents. Stem cell transplant is the oldest treatment modality leveraging immune system in DLBCL. Subsequently, CD20 targeting monoclonal antibody and chimeric antigen receptor (CAR) T-cell therapy changed the treatment landscape of DLBCL. Recently, multiple novel immunotherapeutic agents have been added in the armamentarium for the management of DLBCL, and many are under development. In this review article, we will review latest updates of immunotherapeutic agents in the management of DLBCL.

Cancer Screening During the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

The purpose of this study was to assess the impact of measures designed to mitigate the spread of coronavirus disease 2019 (COVID-19) on worldwide cancer screening. We systematically searched PubMed, Ovid MEDLINE, the Cochrane COVID-19 Study Register, ClinicalTrials.gov, and EMBASE without language restrictions for studies published between January 1, 2021, and February 10, 2021. Studies selected for full-text review contained data on patients screened for any type of cancer during the COVID-19 pandemic and comparison data from a time interval just prior to the pandemic. Data were obtained through dual extraction. All the included studies were assessed for quality and risk of bias. A meta-analysis was performed on 13 studies: 7 on screening mammography, 5 on colon cancer screening, and 3 on cervical cancer screening. Two of our studies reported on more than one type of cancer screening. The screening outcomes were reported as pooled incidence rate ratios using the inverse variance method and random effects models. All studies included in our meta-analysis reported the number of patients screened for cancer in defined time intervals before and during the COVID-19 pandemic. We found that the pooled incidence rate ratios were significantly lower for screening during the COVID-19 pandemic for breast cancer (0.63; 95% CI, 0.53 to 0.77; P<.001), colon cancer (0.11; 95% CI, 0.05 to 0.24; P<.001), and cervical cancer (0.10; 95% CI, 0.04 to 0.24; P<.001). These findings may add further morbidity and mortality to this public health crisis.

KRAS Inhibitors- yes but what next? Direct targeting of KRAS- vaccines, adoptive T cell therapy and beyond.

Kirsten rat sarcoma viral oncogene homolog (KRAS) is a proto-oncogene of the RAS-MAPK pathway. KRAS mutations are present in a variety of malignancies including lung, colorectal, and pancreatic cancer. Until the recent approval of sotorasib, a KRAS G12C inhibitor, lack of targeted therapy for KRAS has resulted in poor prognosis of patients with tumors harboring KRAS mutations. While the conditional approval of sotorasib was a major breakthrough for those patients harboring KRAS G12C mutations, G12C only accounts for a fraction of those with KRAS mutations and eventual resistance to G12C inhibitors are unavoidable. This comprehensive review on KRAS inhibitors covers accumulating evidence on not only the G12C inhibitors but also other therapeutic attempts to tackle KRAS including combination therapy as well as direct inhibition with vaccines, adoptive T cell therapy, proteolysis-targeted chimeras (PROTACs) and CRISPR/Cas9.

Multimodal Intervention Approach Reduces Catheter-associated Urinary Tract Infections in a Rural Tertiary Care Center.

OBJECTIVE: To compare the catheter-associated urinary tract infections (CAUTI) standardized infection rate (SIR) before and after implementation of a multimodal intervention approach in a rural tertiary hospital. DESIGN: Before-after analysis of a multimodal intervention to evaluate primary outcomes of the incidence of inpatient CAUTI, the SIR for CAUTI, and number of urinary catheter days. SETTING: All inpatient departments of a rural 504-bed tertiary care facility in the Midwest. PARTICIPANTS: Patients admitted for in-patient care. INTERVENTIONS: A multimodal intervention composed of: (a) physician and nurse education, (b) modification of progress note templates and daily provider reminders for the clinical necessity of catheters, (c) implementing established best practices for eliminating CAUTIs, (d) advocating for alternative toileting options, and (e) promoting aseptic techniques for insertion and removal of catheters. SIR, CAUTI, and the number of urinary catheter days were obtained before and after implementation of the multimodal intervention in 2015 and 2017, respectively. RESULTS: After a one-year timeframe of intervention, CAUTI event rates decreased, and SIR for CAUTI was reduced by 60.2% (from 1.524 to 0.607) with P value<0.05. Urinary catheter days were also reduced from 16,195 in 2015 to 13,348 in 2017 (17.6% reduction) with P value <0.05. CONCLUSIONS: Incidence of CAUTIs were significantly reduced with a team effort involving infection control, physician and nursing education, modification of progress note and templates and daily provider reminders for the clinical necessity of catheters and appropriate usage of urinary catheter with corresponding reduction in urinary catheter days.

Parvimonas micra bacteremia in a patient with colonic carcinoma.

BACKGROUND: Parvimonas micra is a gram-positive anaerobe and a part of the normal commensal flora of the gastrointestinal tract. Factors predisposing to anaerobic bacteremia include malignant neoplasms, periodontal disease, immune deficiencies, chronic renal insufficiency, decubitus ulcers and perforated abdominal viscus. Cases of Parvimonas bacteremia in a patient with esophageal carcinoma and in a patient following ERCP procedure have been reported but to our best knowledge no case has been reported yet in which a patient had colonic carcinoma. CASE PRESENTATION: We present a rare case of a 94-year-old male who presented with chief complaint of fever and constipation. Complete blood count revealed normal white blood cell count anemia. Urinalysis came out to be unremarkable for any evidence of infection. Two blood cultures grew Parvimonas micra and Gamella morbillorum and patient was later switched to ampicillin-sulbactam as per blood culture susceptibility results. Echocardiogram came negative for any evidence of infective endocarditis. CT abdomen/pelvis showed soft tissue mass in the ascending colon just superior to the ileocecal valve (fig.1, 2). Colonoscopy showed non-obstructing eccentric mass (fig. 3). Biopsy of the mass revealed moderately differentiated adenocarcinoma. Because of lack of distant metastasis, surgical resection of the mass as definitive curative treatment was done. CONCLUSION: Immune deficiency is a risk factor for anaerobic bacteremia. Apart from immediately starting the patient on antibiotics, a thorough search for malignancy may be considered when a patient presents with anaerobic bacteremia, especially, when the source of infection is not known. Identifying malignancy in earliest stages may improve treatment outcome.

Ovarian Cancer Presenting as Cryptogenic Stroke from Patent Foramen Ovale.

A woman, aged 52 years, experienced severe headache, confusion, nausea, dizziness, and diplopia for three days. Magnetic resonance imaging of the brain showed multiple acute and subacute infarcts suggestive of embolic events. Dermatological examination was notable for splinter hemorrhages and macular patches on the fingernails and feet, respectively. Further diagnostic imaging of the chest and abdomen revealed pulmonary emboli and an ovarian mass with omental deposits and splenic infarcts. Fine-needle aspiration cytology and surgery confirmed a diagnosis of high-grade serous adenocarcinoma of the ovary with clear cell features. Extensive evaluation for malignancy should be considered on a case-by-case basis for patients with thromboembolic disease and an initial negative diagnostic evaluation for stroke. Consideration of patent foramen ovale closure is reasonable in patients with malignancy who are at risk for recurrent strokes.

Metastatic Prostate Cancer in a RAD51C Mutation Carrier.

A man, aged 61 years, with a history of hypogonadism and family history of cancer experienced persistent urinary difficulties with no visible prostate abnormalities. Laboratory testing and diagnostic imaging revealed a primary lesion in the prostate with lymph node involvement and multiple bone metastases. Treatment with androgen-deprivation therapy, 17,20-lyase inhibition, and bisphosphonates for 7 months was unsuccessful in preventing disease progression, but second-line chemotherapy and continued androgen-deprivation therapy improved prostate specific antigen levels. During the patient's second treatment regimen, his daughter received a diagnosis of breast cancer. The patient's daughter underwent genetic testing for oncogenic mutations, and it was discovered that she carried a mutation in RAD51C, a gene encoding a protein involved in DNA repair and genomic maintenance. Subsequent genetic testing of the patient revealed mutation in RAD51C as well. For patients with metastatic prostate cancer who are unresponsive to standard treatment and who have a positive family history of cancer, genetic testing may be warranted to develop alternative treatment regimens for the patient and guide family discussions regarding cancer risk. Targeted agents like poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors may be a consideration in prostate cancer patients with DNA repair mutations and with refractory disease.

Distal Tibia and Foot Involvement in a Patient With Waldenstrom's Macroglobulinemia.

Bone lesions are a rare presentation in Waldenstrom's macroglobulinemia patients. Although lytic bone lesions and generalized osteoporosis have been described variably in literature on Waldenstrom's macroglobulinemia patients, distal long bone and foot involvement has not been described to our knowledge. We report a patient with Waldenstrom's macroglobulinemia with IgM monoclonal spike, plasmacytic infiltration of bone marrow, and symptoms of foot pain, and found to have distal tibia and foot involvement. The symptoms of bone lesions in our patient were significantly improved with radiation treatment. The possibility of distal involvement of long bones in a clinically relevant presentation should be kept in mind in these patients.