Tight-binding model predicts exciton energetics and structure for photovoltaic molecules.

Conjugated molecules and polymers are being designed as acceptor and donor materials for organic photovoltaic (OPV) cells. OPV performance depends on generation of free charge carriers through dissociation of excitons, which are electron-hole pairs created when a photon is absorbed. Here, we develop a tight-binding model to describe excitons on homo-oligomers, alternating co-oligomers, and a non-fullerene acceptor - IDTBR. We parameterize our model using density functional theory (DFT) energies of neutral, anion, cation, and excited states of constituent moieties. A symmetric molecule like IDTBR has two ends where an exciton can sit; but the product wavefunction approximation for the exciton breaks symmetry. So, we introduce a tight-binding model with full correlation between electron and hole, which allows the exciton to coherently explore both ends of the molecule. Our approach predicts optical singlet excitation energies for oligomers of varying length as well as IDTBR in good agreement with time-dependent DFT and spectroscopic results.

Hematologic disorders associated with COVID-19: a review.

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.

Paradigm shift in the management of metastatic nonsmall cell lung cancer.

BACKGROUND: Lung cancer is one of the leading causes of cancer mortality in the United States. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced nonsmall cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations and patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. AIMS: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. MATERIALS AND METHODS: A literature search was conducted on Medline (via PubMed) and National Comprehensive Cancer Network Guidelines using the keywords "precision diagnosis," "advanced non-small cell lung cancer," "target therapies," and "immunotherapy." CONCLUSION: The use of next-generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune checkpoint inhibitors (ICI) leading to better survival rates and lesser toxicity.

Tight binding models accurately predict band structures for copolymer semiconductors.

Conjugated polymers possess a wide range of desirable properties including accessible band gaps, plasticity, tunability, mechanical flexibility and synthetic versatility, making them attractive for use as active materials in organic photovoltaics (OPVs). In particular, push-pull copolymers, consisting of alternating electron-rich and electron-deficient moieties, offer broad optical absorption, tunable band gaps, and increased charge transfer between monomer units. However, the large number of possible monomer combinations to explore means screening OPV copolymers by first-principles quantum calculations is computationally intensive. If copolymer band structures could be rapidly computed from homopolymer data, potential materials could be screened more efficiently. In this work, we construct tight binding models of copolymer band structures with parameters determined by density functional theory (DFT) calculations on homopolymers. We use these models to predict copolymer valence and conduction bands, which compare well to direct DFT calculations of copolymer band structures.

Tuning polymer-backbone coplanarity and conformational order to achieve high-performance printed all-polymer solar cells.

All-polymer solar cells (all-PSCs) offer improved morphological and mechanical stability compared with those containing small-molecule-acceptors (SMAs). They can be processed with a broader range of conditions, making them desirable for printing techniques. In this study, we report a high-performance polymer acceptor design based on bithiazole linker (PY-BTz) that are on par with SMAs. We demonstrate that bithiazole induces a more coplanar and ordered conformation compared to bithiophene due to the synergistic effect of non-covalent backbone planarization and reduced steric encumbrances. As a result, PY-BTz shows a significantly higher efficiency of 16.4% in comparison to the polymer acceptors based on commonly used thiophene-based linkers (i.e., PY-2T, 9.8%). Detailed analyses reveal that this improvement is associated with enhanced conjugation along the backbone and closer interchain π-stacking, resulting in higher charge mobilities, suppressed charge recombination, and reduced energetic disorder. Remarkably, an efficiency of 14.7% is realized for all-PSCs that are solution-sheared in ambient conditions, which is among the highest for devices prepared under conditions relevant to scalable printing techniques. This work uncovers a strategy for promoting backbone conjugation and planarization in emerging polymer acceptors that can lead to superior all-PSCs.

Role of Therapeutic Anticoagulation in COVID-19: The Current Situation.

Thrombotic complications from COVID-19 are now well known and contribute to significant morbidity and mortality. Different variants confer varying risks of thrombotic complications. Heparin has anti-inflammatory and antiviral effects. Due to its non-anticoagulant effects, escalated-dose anticoagulation, especially therapeutic-dose heparin, has been studied for thromboprophylaxis in hospitalized patients with COVID-19. Few randomized, controlled trials have examined the role of therapeutic anticoagulation in moderately to severely ill patients with COVID-19. Most of these patients had elevated D-dimers and low bleeding risks. Some trials used an innovative adaptive multiplatform with Bayesian analysis to answer this critical question promptly. All the trials were open-label and had several limitations. Most trials showed improvements in the meaningful clinical outcomes of organ-support-free days and reductions in thrombotic events, mainly in non-critically-ill COVID-19 patients. However, the mortality benefit needed to be more consistent. A recent meta-analysis confirmed the results. Multiple centers initially adopted intermediate-dose thromboprophylaxis, but the studies failed to show meaningful benefits. Given the new evidence, significant societies have suggested therapeutic anticoagulation in carefully selected patients who are moderately ill and do not require an intensive-care-unit level of care. There are multiple ongoing trials globally to further our understanding of therapeutic-dose thromboprophylaxis in hospitalized patients with COVID-19. In this review, we aim to summarize the current evidence regarding the use of anticoagulation in patients with COVID-19 infection.

Therapeutic landscape of advanced HER2-positive breast cancer in 2022.

HER2-positive breast cancer is an aggressive subtype of breast cancer with five-year survival rates of 30% for the advanced stage. The development of anti-HER2 treatments has led to a paradigm shift in the management and clinical outcomes of advanced HER2-positive breast cancer patients. The standard first-line treatment consists of taxane-based chemotherapy plus dual anti-HER2 therapies with trastuzumab and pertuzumab. The antibody-drug conjugate (ADC) ado-trastuzumab emtansine (T-DM1) has been a second-line therapeutic standard, but the second-line treatment approach is rapidly evolving. Given a substantial advantage of another ADC, Fam-trastuzumab deruxtecan (T-DXd), compared to T-DM1 in a recent randomized trial in the second-line setting, T-DXd is currently the preferred second-line option. Optimal third-line treatment strategies are still not established, and multiple approaches have been used including combinations based on capecitabine, trastuzumab, or both with oral anti-HER2 tyrosine kinase inhibitors. Tucatinib plus capecitabine and trastuzumab, lapatinib plus trastuzumab, neratinib or lapatinib plus capecitabine are some of the FDA approved combinations. Another newer agent approved for third- or later-line therapy in the metastatic setting is margetuximab, an Fc-engineered anti-HER2 monoclonal antibody, in combination with chemotherapy. Other novel agents currently under clinical trials are the drugs that indirectly target HER2, including immune cell cycle inhibitors, PI3K/mTOR inhibitors, and immunotherapy agents.

Celiac Plexus Block Complications: A Case Report and Review of the Literature.

Celiac plexus block (CPB) has been widely used as a treatment option for chronic intractable abdominal pain resulting from intra-abdominal malignancies as well as benign conditions. Complications resulting from CPB have been long reported and include diarrhea, back pain, paraplegia, postural hypotension, pneumothorax, and local anesthesia toxicity. Diarrhea and postural hypotension are two most common complications with studies reporting incidences occurring in 44% to 60% and 10% to 52% of patients, respectively. Diarrhea is most often transient, resolving within 48 hours; however, literature reports cases in which diarrhea was chronic, debilitating, and in some instances life threatening. Persistent diarrhea proves difficult to treat. We report a case of a 76-year-old male with unresectable pancreatic adenocarcinoma who underwent computed tomography-guided CBP complicated by persistent diarrhea and fecal incontinence. After conventional antidiarrheal failed to improve the symptoms, octreotide proved to be beneficial and the patient reported significant improvement in symptoms.

To study the contributing factors and outcomes of Clostridioides difficile infection in patients with solid tumors.

BACKGROUND: Clostridioides difficile infection (CDI) is a considerable healthcare burden, and now identified as the leading cause of acquired diarrheal illness in patients receiving antibiotics. Patients with malignancies are more prone to acquire CDI, owing to their frequent exposure to risk factors. OBJECTIVE: This study aims to investigate the factors affecting the outcome of Clostridioides Difficile Infection in patients with solid tumors at our community healthcare center. METHODS: This is a retrospective study that included a total of 59 patients with solid tumors who were hospitalized for Clostridioides difficile infection. RESULTS: The median age of the study population was 79 years with 39 males and 20 females. The patients had a diagnosis of a malignancy involving the following sites: prostate (25), lung (19), colon (7), bladder (4), breast (3), and renal (1). There were 52 cases of first time and 7 cases of recurrent CDI admissions. 40 patients were detected to have CDI at presentation while 19 patients were diagnosed with CDI after admission. CDI was categorized as follows: non-severe (29), severe (28), and very severe (2). There were 33 patients on chemotherapy and 20 patients undergoing radiotherapy. Twenty-seven patients had a recent history of cancer care-related procedures or interventions. Twenty-nine patients were from either a rehabilitation center or a long-term nursing care facility. There were 39 recent hospitalizations with 29 patients receiving antibiotics. Almost half of the patients were on proton pump inhibitors (29) and 12 were on steroids (20.3%) at the time of developing CDI. Patients with a high-risk qSOFA score of 2 or more (p-value = 0.008) or a high white blood cell count of >15 × 109/L (p-value = 0.016) at the time of admission were found to have higher in-hospital mortality. Critical care data suggested that 9 patients required intensive care, 7 patients required vasopressor support, and 6 needed mechanical ventilation. Patients were treated with either vancomycin alone (13), or metronidazole alone (25), or combination therapy with vancomycin + metronidazole (21). The median duration of hospital stay was 6 days with 11 fatalities (18.64%). CONCLUSIONS: CDI causes significant morbidity in patients with malignancies. A high qSOFA score and leukocytosis are significantly associated with high morbidity and thus should be used to prioritize and intensify inpatient care of these patients.

Fungal infections in hematopoietic stem-cell transplant patients: a review of epidemiology, diagnosis, and management.

The advent of bone marrow transplant has opened doors to a different approach and offered a new treatment modality for various hematopoietic stem-cell-related disorders. Since the first bone marrow transplant in 1957, there has been significant progress in managing patients who undergo bone marrow transplants. Plasma-cell disorders, lymphoproliferative disorders, and myelodysplastic syndrome are the most common indications for hematopoietic stem-cell transplant. Despite the advances, invasive fungal infections remain a significant cause of morbidity and mortality in this high-risk population. The overall incidence of invasive fungal infection in patients with hematopoietic stem-cell transplant is around 4%, but the mortality in patients with allogeneic stem-cell transplant is as high as 13% in one study. Type of stem-cell transplant, conditioning regimen, and development of graft-versus-host disease are some of the risk factors that impact the risk and outcomes in patients with invasive fungal infections. Aspergillus and candida remain the two most common organisms causing invasive fungal infections. Molecular diagnostic methods have replaced some traditional methods due to their simplicity of use and rapid turnaround time. Primary prophylaxis has undoubtedly shown to improve outcomes even though breakthrough infection rates remain high. The directed treatment has seen a significant shift from amphotericin B to itraconazole, voriconazole, and echinocandins, which have shown better efficacy and fewer adverse effects. In this comprehensive review, we aim to detail epidemiology, risk factors, diagnosis, and management, including prophylaxis, empiric and directed management of invasive fungal infections in patients with hematopoietic stem-cell transplant.

Current Status of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma.

Multiple myeloma (MM) is an incurable malignancy of plasma cells. Recently multiple new therapeutic options have been introduced which was able to improve overall survival but ultimately patient become refractory specifically in patients with poor cytogenetics. Therefore, novel therapeutic options like immunotherapy are needed to improve outcomes. Chimeric antigen receptor (CAR) T-cell therapy is immunotherapy in which T cell are genetically engineered against a tumor-specific antigen and transfused back to the patient to mount major histocompatibility complex-independent cancer-specific immune response. The success of CAR T-cell therapy in lymphoid malignancies encouraged its development in MM. Most of the clinical studies target B-cell maturation antigen in relapsed refractory MM and relapse is the major issue. In this article, we will present the basics of CAR T-cell therapy, the most recent clinical and preclinical data, and we will discuss the future therapeutic realm of CAR T cells in MM.

Meta-analysis of a master mimicker: endobronchial lipoma.

BACKGROUND: Endobronchial lipomas (ELs) are extremely rare benign tumors that account for 0.1-0.4% of all bronchial tumors. Our study aims to better characterize these lesions based on their baseline demographic characteristics, size, location, association with smoking and establish a treatment modality of choice for such tumors. METHODS: We conducted a retrospective meta-analysis of 29 studies of EL reported from 1994 till present. These 29 studies yielded 36 patient encounters which were included in our study. Categorical outcomes were compared between study groups using chi-square test. P value <0.05 was considered statistically significant. RESULTS: Our study has shown that smaller lesions more likely to be ELs or benign lung tumors. Eighty percent of ELs had a size <1.5 cm (P=0.056) and the other tumor types had a size ≥1.5 cm. CONCLUSIONS: These tumors are difficult to diagnose due to their nonspecific presenting complaints unless pulmonologists maintain a high index of suspicion. Treatment options such surgical resection (SR) or bronchoscopic resection (BR) are available and interventions should be planned on a case-by-case basis by a multidisciplinary team.

Cancer treatment during COVID-19 pandemic.

Currently world is fighting with global pandemic of coronavirus disease 2019 (COVID-19). At this time of uncertainty, oncologists are struggling to provide appropriate care to cancer patients. They have to weigh risk and benefit of giving cancer treatment vs chances of getting them infected with COVID-19. As cancer patients are immunocompromised and there are high chances of exposure during hospital visits and if they get infected, outcome can be fatal. So through the column of this article, we would like to provide basic guideline in management of cancer patients during COVID-19 pandemic.

Current Perspectives on Diagnostic Assays and Anti-PF4 Antibodies for the Diagnosis of Heparin-Induced Thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a recognized clinical entity in patients receiving unfractionated heparin and low-molecular weight heparin. Currently, diagnosing HIT includes the combination of a physician's clinical suspicion based on a clinical scoring system and a series of laboratory tests. In the present article, we discuss challenges in suspecting and diagnosing HIT in consideration of the turnaround time of available tests and recent advances in techniques and methodologies of newer immunoassays and functional assays.

A rare presentation of spontaneous atheroembolic renal disease: A case report.

BACKGROUND: Atheroembolic renal disease (AERD) is caused by occlusion of the small renal arteries from embolized cholesterol crystals arising from ulcerated atherosclerotic plaques. This usually manifests as isolated renal disease or involvement from systemic atheroembolic disease. Here we report a case of AERD that responded well to steroid therapy. CASE SUMMARY: A 62-year-old woman with a history of hypertension and stage IIIa chronic kidney disease was referred for rapidly worsening renal function over a 4-mo period. She complained of swollen legs, dyspnea on exertion, and two episodes of epistaxis about a month prior to admission. She reported no history of invasive vascular procedures, use of radio contrast agents, or treatment with anticoagulants or thrombolytic agents. Urinalysis showed a few red blood cells and granular casts. Serology was positive for cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA). Non-contrast-enhanced computed tomography of the chest, abdomen, and pelvis showed diffuse atherosclerotic changes in the aortic arch. Thus, c-ANCA-associated vasculitis was suspected, and the patient was started on pulse intravenous methylprednisolone. Her renal biopsy showed evidence of AERD. She was discharged with oral prednisone, and her renal function continued to improve during the initial follow-up. CONCLUSION: In cases of non-vasculitis-associated ANCA, a high degree of clinical suspicion is required to pursue the diagnosis of spontaneous AERD in patients with clinical or radiological evidence of atherosclerotic burden. Although no specific treatment is available, the potential role of statins and steroids requires exploration.

Anti PD-1 immunotherapy related interstitial lung disease presenting as respiratory failure - A review with case series.

INTRODUCTION: Lung cancer is one of the most common cancers in the world and it is the leading cause of cancer-related deaths, among men and women, in the United States. In advanced non-small cell lung cancers, immune checkpoint inhibitors such as programmed cell death protein-1 inhibitors (PD-1 inhibitors) have become second-line therapy and have revolutionized the management in selective cases conferring better overall response rates and progression free survival. METHODS: We present a case series and review of literature emphasizing this immune-related adverse events (irAEs) in patients with metastatic non-small cell lung cancer and esophageal cancer who were treated with Nivolumab as a second line therapeutic option. RESULTS: PD-1 inhibitors such as, Nivolumab and Pembrolizumab, have shown a stable regression of various malignancies, such as metastatic melanoma, renal cell carcinoma and metastatic non-small cell lung cancer. We describe 2 cases of such immune related adverse effects associated with immune check point inhibitors with recovery in one of the patients. Steroid therapy has been the cornerstone for treatment for such immune related adverse effects. Importance has also been laid on the typical radiographic patterns of pneumonitis and interstitial lung disease associated with immunotherapy. CONCLUSIONS: We attempt to raise awareness, discuss early management strategies and hypothesize an association between the incidence and development of these adverse events in cancer patients treated with anti-PD-1 immunotherapeutic agents.

Pancytopenia: A Rare and Unusual Initial Presentation of Breast Cancer.

Bone marrow metastasis with profound pancytopenia is an extremely uncommon presentation of breast cancer. Advanced breast cancer can frequently metastasize to bone marrow, but bone marrow failure is not typically seen. Very limited data exist regarding the appropriate management of patients with metastatic breast cancer with profound pancytopenia. Our patient's initial presentation of anemia and thrombocytopenia was a diagnostic dilemma, later confirmed as metastatic breast cancer on bone marrow biopsy. After diagnosis, treatment was another challenge as there are no predefined treatment guidelines for these patients. After the initial hormonal therapy failed, our patient showed a good clinical response to chemotherapy and her platelet count improved to baseline. This dramatic response to chemotherapy is rare. Therefore, this case represents a rare instance of a diagnostic and therapeutic dilemma with unusual clinical response to chemotherapy.

Dying to be Ill: Munchausen meets warfarin overdose.

Patients with severe coagulopathy related to vitamin K deficient proteins can be associated with surreptitious ingestion of vitamin K antagonists. Our patient presented acutely with extensive ecchymosis, gingival bleeding and hematuria. Her initial PT and PTT were prolonged and INR was >12.0. She denies contact with potent rodenticides or warfarin use. She is a healthcare professional. Within a week, she was readmitted with similar complaints and her warfarin levels were markedly high which raised the possibility of Munchausen syndrome. Warfarin overdose can lead to harmful consequences. Therefore, immediate diagnosis and prompt treatment is critically important to minimize morbidity and mortality.