Background: Immune checkpoint inhibitors (ICIs) are a class of anticancer drugs. ICIs have revolutionized cancer therapy by enhancing the immune system’s ability to target tumors. However, they carry a risk of immune-related adverse effects, including interstitial lung disease (ILD). Steroid-refractory ILD in patients undergoing ICI treatment represents a serious condition in which ILD does not respond to standard steroid therapy, requiring alternative management strategies. This systematic review and meta-analysis address the prevalence, characteristics, and outcomes of steroid-refractory ILD in patients undergoing ICI treatment. Methods: A systematic, comprehensive computer search of available literature in various databases was performed; four researchers independently reviewed the articles and excluded ones that did not fit the predetermined eligibility criteria. Results: The analysis covered 2359 patients across 19 studies. We found that the pooled prevalence of steroid-refractory CIP was 12% (95% confidence interval [CI]: 3%–24%). Among patients with lung cancer, the pooled prevalence was 24% (95% CI: 9%–43%), while it was 16% among patients with hematologic malignancies. Higher prevalence was found among males (69%) and smokers (63%) compared to females (38%) and nonsmokers (40%). The pooled mortality rate among patients with steroid-refractory CIP was 32% (95% CI: 12%–55%). Conclusions: Overall, our research emphasizes the need for early detection, careful monitoring, and customized treatment approaches for managing this serious complication, urging further research to refine management strategies and improve patient outcomes.

The intent of this correspondence is to highlight the critical situation confronting the Palestinian population residing in Gaza, particularly in the northern governorates, characterized by acute shortages of food and water.

Abstract Introduction Pulmonary arterial hypertension (PAH) is a severe and life-threatening condition characterized by increased pulmonary vascular resistance and elevated mean pulmonary artery pressure. Treprostinil, a prostacyclin analog, has vasodilatory and anti-remodeling effects on pulmonary arterial smooth muscle cells, indicating promising benefits in enhancing exercise capacity, improving hemodynamics, and reducing morbidity in patients with PAH. Aim The primary objective of this systematic review and Meta-analysis is to assess the efficacy and safety of Treprostinil in patients with PAH. Methods We systematically searched PubMed, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov from inception until July 2023. Randomized controlled trials comparing Treprostinil with Placebo were selected. We used the mean values to compare continuous data and odds ratio (OR) for dichotomous outcomes with their 95% confidence interval (CI). Results We included 7 studies with a total of 2,447 patients. The Treprostinil group was favored over the control group in terms of 6-minute walk distance (6MWD) (Mean difference (MD), meters (m)) (MD = 15.16 m, 95% confidence interval (CI) (10.42 – 19.90 )). Subgroup analysis based on the route of administration revealed a 6MWD of (MD = 13.55 m (95% CI (7.82 – 19.28)) for oral administration and (MD = 17.49 m, 95% CI (6.01 – 28.89)) for intravenous (IV)/subcutaneous (SC) administration, indicating enhanced exercise capacity. When evaluating the efficacy of Treprostinil for oral administration, there was a slight but non-significant trend toward functional improvement (Odds Ratio (OR): 1.36; 95% CI: 0.95 to 1.93) and no significant change in maintaining functional status (OR: 0.94; 95% CI: 0.59 to 1.51). In terms of functional deterioration, the risk was also not significantly reduced (OR: 0.84; 95% CI: 0.36 to 1.98). Safety assessment of the drug was based on clinical, mortality, and adverse events outcomes. Clinically, Treprostinil demonstrated a protective effect against disease progression, evidenced by a reduced risk of clinical worsening (OR: 0.69; 95% CI: 0.52 to 0.91). Mortality rates were not significantly impacted by Treprostinil addition (OR: 0.95; 95% CI: 0.57 to 1.58 for oral, 0.80; 95% CI: 0.32 to 1.98 for IV/SC). However, the incidence of adverse events was notably higher among Treprostinil-treated patients, particularly with oral administration. Conclusion The addition of Treprostinil therapy for patients with PAH significantly improved exercise capacity, as evidenced by an increase in the 6MWD compared to control groups and demonstrated a reduced risk of clinical worsening. The incidence of adverse events was higher among Treprostinil-treated patients, especially with oral administration, potentially impacting quality of life.Forest plot of the 6MWD

Anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis is a prevalent autoimmune condition marked by diverse neuropsychiatric symptoms, primarily impacting young females. The exact mechanisms underlying the development of NMDAr encephalitis have not been fully elucidated. Nonetheless, studies have demonstrated that auto-antibodies targeting the NR1-NR2 subunits of the NMDAr can trigger receptor dysfunction within the central nervous system, thus giving rise to the associated symptoms. Notably, an association exists between NMDAr encephalitis and an underlying neoplastic condition, with approximately 38% of cases exhibiting this paraneoplastic relationship with ovarian teratomas being the most commonly associated malignancy.While the association between NMDAr encephalitis and renal cell carcinoma (RCC) is exceedingly rare. This case report presents the clinical scenario of a 20-year-old female patient diagnosed with NMDAr encephalitis in conjunction with RCC discovered incidentally on a CT abdomen and pelvis performed to rule out an ovarian teratoma. The presented case underscores the importance of adopting a multidisciplinary approach in the diagnosis and treatment of NMDAr encephalitis, particularly when it is linked to an underlying malignancy. Furthermore, it emphasizes the significance of expanding our understanding of the molecular pathogenesis of NMDAr encephalitis to enhance patient care and optimize clinical outcomes. Additionally, a comprehensive review of the existing literature is included, summarizing all reported malignancies associated with NMDAr encephalitis.

Background:Heart failure (HF) and breast cancer are major health concerns with overlapping risk factors. This study investigated the impact of breast cancer on in-hospital mortality, length of stay, and health care charges in patients with HF. Methods:A retrospective cohort study was conducted using data from the National Inpatient Sample, focusing on female patients diagnosed with both breast cancer and HF. A control group of patients with HF without breast cancer was also analyzed. Main outcomes included in-hospital mortality, length of stay, and health care charges. Statistical analysis involved logistic and linear regression models. Results:The study included 17,551 unweighted cases of breast cancer, corresponding to 87,755 weighted cases. Breast cancer, particularly metastatic, was associated with increased in-hospital mortality across various types of HF. Patients with breast cancer and HF had longer hospital stays, which was more pronounced in metastatic cases. However, the impact on hospital charges was not consistent across the different HF types. Racial disparities were evident, with Native Americans showing the highest mortality risk in acute HF. Conclusion:Breast cancer significantly increases the in-hospital mortality risk and length of hospital stay in patients with HF. These findings highlight the need for integrated cardiovascular and oncological care, especially in the presence of metastatic breast cancer. The study underscores the importance of tailored management strategies for patients with HF with concurrent breast cancer and points toward the necessity for addressing racial disparities in health care.

Background and aim: Sarcoidosis of the central nervous system (CNS) often presents deleterious effects on affected patients. Data and available literature discussing the diagnosis and treatment of this condition are scarce and inconsistent. In this study, we aim to shed light on demographics, management, diagnostics, and clinical complications of CNS sarcoidosis patients within the United States (US) based on a nation-wide registry questionnaire. Methods: Our retrospective study was conducted based on a national registry investigating 3,835 respondents to the Foundation for Sarcoidosis Research Sarcoidosis Advanced Registry for Cures Questionnaire (FSR-SARC). This national registry data was collected during the period of June 2014 to August 2019. We performed propensity score matching, summary, univariate, and multivariate analyses to establish a comparison between the presence and absence of central nervous system sarcoidosis. Results: We identified a total of 420/3634 (11.55%) patients having CNS sarcoidosis; 296 (70.5%) were females, 307 (73.1%) were Caucasian and 81 (19.3%) were African American. The mean (+/- SD) age at diagnosis of CNS sarcoidosis was 43.3 (+/- 12) years old. Multiorgan involvement (>= 3 organs) was present in 318/420 (75.7%) patients. Brain magnetic resonance imaging was the most common ancillary diagnostic modality used and reported to be abnormal 251/328 (76.5%). Corticosteroids were the most used treatment by CNS sarcoidosis patients 206/420 (49.0%) followed by cytotoxic agents 180/420 (42.9%). Conclusions: CNS sarcoidosis prevalence in our cohort was similar to what has been described previously. The most prevalent imaging modality used was cranial MRI. Corticosteroids were the most used medications. Lastly, CNS sarcoidosis showed a propensity to cause several clinical complications such as chronic pain syndrome and disability.

Background and Objectives: Gabapentin has shown promise as a potential agent for the treatment of alcohol withdrawal syndrome. We aimed to evaluate the effectiveness of gabapentin as a benzodiazepine-sparing agent in patients undergoing alcohol withdrawal treatment in all the hospitals of a large tertiary healthcare system. Materials and Methods: Medical records of patients admitted to the hospital for alcohol withdrawal management between 1 January 2020 and 31 August 2022 were reviewed. Patients were divided into two cohorts: benzodiazepine-only treatment who received benzodiazepines as the primary pharmacotherapy and gabapentin adjunctive treatment who received gabapentin in addition to benzodiazepines. The outcomes assessed included the total benzodiazepine dosage administered during the treatment and the length of hospital stay. The statistical models were calibrated to account for various factors. Results: A total of 4364 patients were included in the final analysis. Among these, 79 patients (1.8%) received gabapentin in addition to benzodiazepines, and 4285 patients (98.2%) received benzodiazepines only. Patients administered gabapentin required significantly lower average cumulative benzodiazepine dosages, approximately 17.9% less, compared to those not receiving gabapentin (median 2 mg vs. 4 mg of lorazepam equivalent dose (p < 0.01)). However, there were no significant differences in outcomes between the two groups. Conclusions: Our findings demonstrate that using gabapentin with benzodiazepine was associated with a reduction in the cumulative benzodiazepine dosage for alcohol withdrawal. Considering gabapentin as an adjunctive therapy holds promise for patients with comorbidities who could benefit from reducing benzodiazepine dose. This strategy warrants further investigation.

PURPOSE: Cutaneous involvement is a common manifestation of sarcoidosis estimated to occur in up to a fourth of all patients.We aim to describe the demographics and clinical characteristics of patients with cutaneous manifestations of sarcoidosis in the United States based on a national registry questionnaire. METHODS:We conducted a retrospective study based on a national registry investigating 3,835 respondents to the Foundation for Sarcoidosis Research -Sarcoidosis Advanced Registry for Cures Questionnaire (FSR-SARC).The registry includes patient surveys completed between June 2014 and August 2019.Summary and univariate analyses were performed.RESULTS: A total of 917 (24%) patients with sarcoidosis with a mean (AESD) age of 55 (AE12) had cutaneous manifestations; 81% (n¼741) were females and 72% (n¼660) were Caucasian.Patients with cutaneous manifestations were more likely to be female (81% vs 72%, p<0.0001) and Black (24% vs 14%; p<0.0001).There was no significant difference in age between patients with and without cutaneous manifestations (p¼0.55).A dermatologist evaluated 50% (n¼461) of these patients and a skin biopsy was performed in 27% (n¼250).A kviem test was performed in 135 patients (15%).Multiorgan involvement ($3 organs) was present in 724 patients (79%).Patients with cutaneous manifestations had significantly higher odds of multiorgan involvement (OR:5.5, 95%CI: 4.6-6.7,p<0.0001).The most common cutaneous manifestations include plaques (n¼384, 42%), abnormal skin pigmentation (n¼265, 29%), lupus pernio (n¼250, 27%), scar and tattoo sarcoidosis (n¼221, 24%), papules (n¼214, 23%) and erythema nodosum (n¼181, 20% of which n¼87, 48% had Lofgren syndrome).Most patients received systemic steroids (n¼708, 77%) and topical steroids (n¼211, 23%).Other medications administered include cytotoxic medication (n¼491, 54%), of which methotrexate was most used (n¼331, 36%), hydroxychloroquine/chloroquine (n¼305, 33%) and tumor necrosis factor (TNF) inhibitors (n¼153, 17%) of which infliximab was the most used (n¼110, 12%).Patients with cutaneous manifestations were more likely to have received hydroxychloroquine (OR: 3.2, 95%CI: 2.6-4.0,p<0.0001), cytotoxic agents (OR: 2.9, 95%CI: 1.7-2.5, p<0.0001) and TNF inhibitors (OR:1.7,95%CI: 1.3-2.2,p<0.0001).There was no significant difference in systemic steroid use between patients with and without cutaneous manifestations (OR:1.2,95%CI: 1.0-1.4,p¼0.1).Other rare therapies include minocycline/doxycycline (n¼12), corticosteroid skin injections (n¼8), topical tacrolimus (n¼3), laser surgery using carbon dioxide (n¼2), thalidomide (n¼2) and laser pulse therapy (n¼1).CONCLUSIONS: Cutaneous manifestations of sarcoidosis are prevalent, especially in Black females, and are associated with systemic disease.Steroids, methotrexate, hydroxychloroquine and infliximab are the most common medication used.CLINICAL IMPLICATIONS: Cutaneous manifestations of sarcoidosis are more prevalent in Black females, are associated with systemic disease, and frequently require systemic therapy.

Download This Paper Open PDF in Browser Add Paper to My Library Share: Permalink Using these links will ensure access to this page indefinitely Copy URL Copy DOI

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAr) encephalitis is a rare autoimmune disorder with neuropsychiatric symptoms that primarily affects young females.Its diagnosis is underreported and challenging for healthcare providers.The mechanism behind the development of the disease is not fully understood, but studies suggest that auto-antibodies to the NR1-NR2 subunits of NMDAr can lead to downregulation of the receptor and symptoms.NMDAr encephalitis may be associated with an underlying malignancy, and its treatment requires a multidisciplinary team.This case report presents a 20year-old female with NMDAr encephalitis associated with renal cell carcinoma.The patient required a collaborative approach to diagnosis and treatment.The report highlights the need for further understanding of the molecular pathogenesis of NMDAr encephalitis to improve patient outcomes. CASE PRESENTATION:A 20-year-old female presented to the hospital with severe neuropsychiatric symptoms, including agitation, hyperkinetic movements, and autonomic dysfunction.She had multiple visits to the emergency room without an accurate diagnosis and eventually self-medicated with alcohol.Upon presentation to our hospital, the patient was in severe distress and required mechanical ventilation for acute hypoxic respiratory failure and rhabdomyolysis from hyperkinetic movements.A detailed workup was performed in the ICU, brain magnetic resonance imaging revealed increased T2 and FLAIR hyperintensity in the bilateral amygdala and corticospinal tracts (Figure 1).To identify the cause of her worsening condition, a lumbar puncture with a thorough analysis of her cerebrospinal fluid (CSF) was conducted, including testing for arboviral and anti-N-methyl-D-aspartate (NMDA) receptor titers.Testing for paraneoplastic autoantibodies using the Mayo Clinic paraneoplastic Antibody Panel (Mayo Medical Laboratories Test ID: PAVAL) was done.The patient required sedation, paralysis medications, and mechanical ventilation to manage her choreiform movements and rhabdomyolysis.The test of anti-N-methyl-D-aspartate receptor in serum and CSF was positive (1:640 Serum; 1:320 CSF).In light of previous studies linking anti-N-methyl-D-aspartate (NMDA) receptor encephalitis to ovarian teratomas, a malignancy screening with a CT scan of the abdomen and pelvis, as well as a transvaginal ultrasound, was performed.However, no evidence of ovarian pathology was identified by the CT scan or ultrasound examination.Instead, a left renal mass (6.1x5.6x5.4 cm) consistent with a probable Renal Cell Carcinoma was detected (Figure 2) later confirmed by biopsy.The patient required a multidisciplinary team of surgeons, oncologists, intensivists, neurologists, hematologists, and radiologists to find the best approach to her treatment, which consisted of total nephrectomy with excision of RCC, followed by steroids, plasma exchange, and immunotherapy.The patient improved and remained under observation.DISCUSSION: Anti-NMDAr encephalitis is now considered to be part of a group of autoimmune encephalitis that target NMDA receptors proteins.The diagnosis of NMDAr encephalitis is suspected based on acute to subacute clinical presentation and patient population.This is confirmed with detection of immunoglobulin G antibodies to NR1/NR2 subunit of NMDAr in the CSF and/or blood.Anti-NMDAr encephalitis remains underrecognized in many centers and it is usually reported in the setting of ovarian teratoma.The association of this condition with RCC is extremely rare with very few cases reported in literature.CONCLUSIONS: Anti-NMDA receptor encephalitis can be associated with RCC.

BACKGROUND:The use of echocardiography in pulmonary hypertension (PH) in advanced chronic obstructive pulmonary disease (COPD) is understudied. We aimed to compare the performance of echocardiography with right heart catheterization (RHC) in the diagnosis of PH in COPD patients undergoing lung transplant evaluation. METHODS:We included 111 patients with severe COPD who underwent RHC in a single center as part of lung transplantation evaluation. COPD-PH and severe COPD-PH were defined based on RHC per the 6th world symposium on pulmonary hypertension. Echocardiographic probability of PH was described according to the European Society of Cardiology guidelines. Summary and univariate analyses were performed. RESULTS:The mean age (±SD) was 62 (8) and 47% (n=52) were men. A total of 82 patients (74 %) had COPD-PH. The sensitivity, specificity, positive predictive, and negative predictive values of echocardiography in diagnosing COPD-PH were 43 %, 83 %, 88 %, and 34 % respectively and for severe COPD-PH were 67 %, 75 %, 50 %, and 86 % respectively. Echocardiography was consistent with RHC in ruling in/out PH in 53% (n=59) of patients. After controlling for age, sex. BMI, pack year, echocardiography-RHC time difference, GOLD class, FVC, and CT finding of emphysema, higher TLC decreased consistency (parameter estimate=-0.031; odds ratio: 0.97, 95%CI 0.94-0.99; p=0.037) and higher DLCO increased consistency (parameter estimate=0.070; odds ratio: 1.07, 95%CI 0.94-0.99; p=0.026). CONCLUSIONS:Echocardiography has high specificity but low sensitivity for the diagnosis of PH in advanced COPD. Its performance improves when ruling out severe COPD-PH. This performance correlates inversely with lung hyperinflation.

BACKGROUND:Diagnosis of interstitial lung disease (ILD) is based on multidisciplinary team discussion (MDD) with the incorporation of clinical, radiographical, and histopathologic information if available. We aim to evaluate the diagnostic yield and safety outcomes of transbronchial lung cryobiopsy (TBLC) in the diagnosis of ILD. METHODS:We conducted a meta-analysis by comprehensive literature search to include all studies that evaluated the diagnostic yields and/or adverse events with TBLC in patients with ILD. We calculated the pooled event rates and their 95% confidence intervals (CIs) for the diagnostic yield by MDD, histopathologic diagnostic yield, and various clinical adverse events. RESULTS:We included 68 articles (44 full texts and 24 abstracts) totaling 6386 patients with a mean age of 60.7±14.1 years and 56% men. The overall diagnostic yield of TBLC to achieve a definite or high-confidence diagnosis based on MDD was 82.3% (95% CI: 78.9%-85.2%) and histopathologic diagnosis of 72.5% (95% CI: 67.7%-76.9%). The overall rate of pneumothorax was 9.6% (95% CI: 7.9%-11%), while the rate of pneumothorax requiring drainage by a thoracostomy tube was 5.3% (95% CI: 4.1%-6.9%). The rate of moderate bleeding was 11.7% (95% CI: 9.1%-14.9%), while the rate of severe bleeding was 1.9% (95% CI: 1.4%-2.6%). The risk of mortality attributed to the procedure was 0.9% (95% CI: 0.7%-1.3%). CONCLUSION:Among patients with undiagnosed or unclassified ILD requiring tissue biopsy for diagnosis, transbronchial cryobiopsy represents a reliable alternative to surgical lung biopsy with decreased incidence of various clinical adverse events.

PURPOSE: Diabetes mellitus (DM) is a known risk factor for HF, and individuals with diabetes are at an increased risk for developing heart failure and requiring a Left ventricular assist device (LVAD).The aim of this study is to investigate the effect of DM on patients receiving LVAD therapy, with a primary outcome of in-hospital mortality, and secondary outcomes including cost of hospitalization and length of hospital stay. METHODS:The current investigation is a retrospective cohort design, utilizing data sourced from the National Inpatient Sample (NIS) administrative database.The study population is adult (aged 18 and above) hospitalized heart failure patients who had undergone implantation of left ventricular assist devices.Exclusion criteria included patients under 18 years old and those who had undergone cardiac transplant during the index admission.The primary outcome was mortality during the index hospitalization, and secondary outcomes included length of stay and cost of admission.Weighted samples were used for national estimates, and multivariate logistic regression was conducted to adjust for confounding variables including age, sex, race, and comorbidities, with odds ratios and 95% confidence intervals reported.The data was analyzed using complex models that took into account homoscedasticity considering the various clusters and strata.Associations were considered significant if the P-value was <0.05.The data was analyzed using SAS version 9.4 Cary North Carolina. RESULTS:The study analyzed a sample of 10,815 adult patients with heart failure and LVADs, of which 44.28% had diabetes.The diabetic patients were found to have shorter length of hospital stay and lower cost of admission, but showed a higher inhospital mortality rate in comparison to non-diabetic patients when controlling for various demographic and clinical factors.However, when adjusting for all comorbidities, there was no significant difference in in-hospital mortality between the two groups.CONCLUSIONS: Our current study, utilizing a large retrospective cohort design and being the largest study to date to assess this relationship, aimed to investigate the impact of diabetes mellitus (DM) on outcomes in patients receiving left ventricular assist devices (LVADs).The results of our analysis indicate that there is no statistically significant difference in the primary outcome of in-hospital mortality between diabetic and non-diabetic patients.This finding is of particular interest, as previous studies investigating the relationship between DM and LVAD have yielded conflicting results. CLINICAL IMPLICATIONS:The impact of diabetes mellitus (DM) on outcomes following LVAD implantation remains uncertain, with many transplant centers considering the presence of complicated DM as a relative contraindication for heart transplantation (DOI: 10.1016/j.healun.2015.10.023).However, this approach may unjustly restrict access of diabetic patients to a treatment modality that has been shown to improve survival and quality of life in select patient populations.