A Paradigm Shift in Non-Small-Cell Lung Cancer (NSCLC) Diagnostics: From Single Gene Tests to Comprehensive Genomic Profiling.

Lung cancer imposes a burden on the health care system worldwide affecting 2 million people and causing 1.8 million deaths in 2021.More than 85% of all lung cancer cases are reported under Non-small-cell lung cancer (NSCLC). It is critical to discover gene alterations to treat non-small cell lung cancer successfully. The CAP/IASLC/AMP recommendations supported use of polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) EGFR (epidermal growth factor receptor) mutations and ALK (Anaplastic lymphoma kinase) rearrangements, respectively. A study presented in the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago emphasized the need for comprehensive genomic profiling (CGP) before single gene tests (SGTs) since it demonstrated that SGT can result in the depletion of precious biopsy samples. As a result, the efficacy of thorough genetic Profiling (CGP) is reduced, preventing patients from receiving valuable genetic information about their tumors.

CRP Albumin Ratio: A novel noninvasive and cost-effective method for assessing the severity of acute pancreatitis.

Introduction: Acute pancreatitis is a significant and potentially life-threatening gastrointestinal disorder that requires prompt and accurate diagnosis for effective treatment. Current diagnostic methods often involve expensive and inaccessible imaging studies, such as CT scans, limiting their utility in emergency settings and underserved areas. Aim: This correspondence discusses an innovative and cost-effective approach to assessing the severity of acute pancreatitis, focusing on the C-Reactive Protein-Albumin Ratio (CAR). Methodology: We searched relevant articles and studies from 2015 till date on PubMed, Web of Science, and Google Scholar using these keywords: "C-Reactive Protein", "Albumin Ratio", "Acute pancreatitis", "Cost-effective", "Non-invasive", and "Severity". Result: The CAR diagnostic method involves a simple blood test that measures the levels of C-Reactive Protein (CRP) and albumin, both commonly used markers for assessing inflammation. Elevated CRP and decreased albumin levels are indicative of inflammation, and the CAR has shown a strong positive correlation with the severity of acute pancreatitis. This method offers a non-invasive, time-efficient, and cost-friendly alternative to traditional diagnostic techniques. Conclusion: The potential of CAR as an assessment tool for the severity of acute pancreatitis is highlighted, especially in resource-limited settings. This innovation holds promise for improving the timely and accurate diagnosis of acute pancreatitis, ultimately enhancing patient outcomes and reducing mortality rates.

Therapeutic approaches for spinal synovial sarcoma: a comprehensive review of the literature.

OBJECTIVE: Synovial sarcoma (SS) is a relatively rare type of soft-tissue sarcoma that is commonly treated with surgery, radiation, chemotherapy, and palliative care. Stereotactic radiosurgery (SRS) is an emerging approach that shows promise in treating CNS conditions, but it has not been studied for SS. The authors present a systematic review that explores the effectiveness of different treatments, with a focus on SRS, for managing spinal SS. METHODS: A systematic PubMed search was conducted that covered studies from 1964 to 2022, yielding 70 relevant studies. Inclusion criteria encompassed primary and metastatic spinal SS, various treatment modalities, patient age 17 years or older, English-language studies, retrospective series, and case reports. Based on these criteria, 26 studies were included in this review and 44 were excluded. RESULTS: Of the included studies, 15 patients from 9 studies were treated with surgical intervention followed by both conventional radiotherapy (RT) and chemotherapy, 10 patients from 10 studies were treated with surgery followed by RT, 5 studies comprising 8 patients were exclusively treated with surgery, 5 cases in 3 studies were treated with surgery plus concomitant chemotherapy, 4 patients in 2 studies were treated with SRS, and only 1 study reported treatment without surgery and with chemotherapy and RT. The median progression-free survival and overall survival periods observed in the SRS-treated patients were 37 months and 60 months, respectively, which were higher than those of any other treatment method or combination used. CONCLUSIONS: The authors' study offers a thorough review of spinal SS treatments. They are hopeful that this will aid clinicians in informed decision-making for better patient outcomes.

Left Atrial Strain as a Predictor of Early Anthracycline-Induced Chemotherapy-Related Cardiac Dysfunction: A Pilot Systematic Review and Meta-Analysis.

Background: Chemotherapy-related cardiac dysfunction (CTRCD) significantly affects patients undergoing anthracycline (AC) therapy, with a prevalence ranging from 2% to 20%. Reduced left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LV GLS) are prognostic parameters for CTRCD detection. Our study aimed to investigate the role of emerging parameters such as left atrial strain (LAS). Methods: We searched multiple databases for studies comparing LAS changes post-AC versus pre-AC therapy in patients with cancer. Primary outcomes included left atrial reservoir strain (LASr), left atrial conduit strain (LAScd), and left atrial contractile strain (LASct). RevMan (v5.4) was used to pool the standardized mean difference (SMD) under a random effects model, with p < 0.05 as the threshold for statistical significance. Results: In an analysis of 297 patients across five studies, AC therapy significantly lowered LASr (SMD = -0.34, 95% CI:-0.55, -0.14, I2 = 0%, p = 0.0009) and LAScd (SMD = -0.41, 95% CI: -0.59, -0.23, I2 = 0%, p < 0.00001) levels. Conversely, LASct demonstrated no significant change (SMD = 0.01, 95% CI: -0.21, 0.23, I2 = 9%, p = 0.95). AC therapy also significantly reduced LV GLS (SMD = -0.31, 95% CI: -0.51, -0.11, I2 = 0%, p = 0.003). While not statistically significant, LVEF decreased (SMD = -0.20, 95% CI: -0.42, 0.03, I2 = 0%, p = 0.09), and left atrial volume index trended higher (SMD = 0.07, 95% CI: -0.14, 0.27, I2 = 0%, p = 0.52) after AC therapy. Conclusions: AC treatment led to reduced LAS and LV GLS values, indicating its potential as an early CTRCD indicator. Larger trials are required to fully explore their clinical significance.

Controversies and Future Directions in Management of Acute Appendicitis: An Updated Comprehensive Review.

Globally, acute appendicitis has an estimated lifetime risk of 7-8%. However, there are numerous controversies surrounding the management of acute appendicitis, and the best treatment approach depends on patient characteristics. Non-operative management (NOM), which involves the utilization of antibiotics and aggressive intravenous hydration, and surgical appendectomy are valid treatment options for healthy adults. NOM is also ideal for poor surgical candidates. Another important consideration is the timing of surgery, i.e., the role of interval appendectomy (IA) and the possibility of delaying surgery for a few hours on index admission. IA refers to surgical removal of the appendix 8-12 weeks after the initial diagnosis of appendicitis. It is ideal in patients with a contained appendiceal perforation on initial presentation, wherein an initial nonoperative approach is preferred. Furthermore, IA can help distinguish malignant and non-malignant causes of acute appendicitis, while reducing the risk of recurrence. On the contrary, a decision to delay appendectomy for a few hours on index admission should be made based on the patients' baseline health status and severity of appendicitis. Post-operatively, surgical drain placement may help reduce postoperative complications; however, it carries an increased risk of drain occlusion, fistula formation, and paralytic ileus. Furthermore, one of the most critical aspects of appendectomy is the closure of the appendiceal stump, which can be achieved with the help of endoclips, sutures, staples, and endoloops. In this review, we discuss different aspects of management of acute appendicitis, current controversies in management, and the potential role of endoscopic appendectomy as a future treatment option.

"Veozah (Fezolinetant): A Promising Non-Hormonal Treatment for Vasomotor Symptoms in Menopause".

Vasomotor symptoms (VMS) are a common and distressing experience during menopause, affecting a significant portion of women. Hormone therapy (HT) has been the traditional treatment, but its limitations and potential risks have led to the search foar non-hormonal alternatives. Recently, the FDA approved Veozah (Fezolinetant) as a promising nonhormonal solution for moderate to severe VMS in menopause. Veozah, an innovative neurokinin 3 (NK3) receptor antagonist, targets the disrupted thermoregulation underlying VMS. It modulates neural activity within the thermoregulatory center by crossing the blood-brain barrier, offering relief from hot flashes and night sweats. Clinical trials, including SKYLIGHT 1TM, SKYLIGHT 2TM, and SKYLIGHT 4TM, have established Fezolinemtant's efficacy and safety profile. The recommended dosage of one 45 mg tablet per day demonstrates proportional pharmacokinetics, with generally mild side effects that require regular monitoring. Fezolinetant's oral availability makes it a convenient and accessible option for women seeking relief from VMS, potentially improving their overall well-being.

Inflammation of actinic keratosis from chemotherapy in a relapsed multiple myeloma patient.

A man in his 60 s with a history of actinic keratosis (AK) and relapsed IgG kappa multiple myeloma (MM) recently received VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) chemotherapy and presented with numerous haemorrhagic, scaly lesions on his scalp and face. He also had sepsis from methicillin-sensitive Staphylococcus aureus (MSSA) bacteraemia. Since the lesions were only present in the areas of pre-existing AK, a diagnosis of inflammation of AK secondary to chemotherapy was made. Sepsis was treated with appropriate antibiotics, and inflammation of AK was managed with topical steroids, leading to complete recovery.

Efficacy analysis of different FLT3 inhibitors in patients with relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndrome.

Several FLT3 inhibitors(i) are available to treat relapsed/refractory (R/R) FLT3-internal tandem duplicated acute myeloid leukemia (AML). This study analyzes the efficacies of various FLT3i (types 1 and 2) tested in clinical trials in treating R/R AML and high-risk myelodysplastic syndromes (HR-MDS). PubMed and EMBASE databases were searched for single/double-arm phase I/II/III R/R AML or HR-MDS clinical trials published between 1/1/2000 and 6/1/2021. The outcomes studied were composite response rate (CRc) and overall response rate (ORR). Toxicities were compared based on the organ system. The 28 studies analyzed had 1927 patients. The pooled ORR and (CRc) for all FLT3i were 53% (95% CI, 43%-63%) and 34% (95% CI, 26%-44%). Pooled ORR and CRc were 37% (95% CI, 25%-51%) and 35% (95% CI, 21%-52%) for type 1 and 58% (95% CI, 43%-71%) and 38% (95% CI, 27%-50%) for type 2, respectively. Gastrointestinal (GI) and hematological toxicity occurred in 22% (95% CI, 19%-25.4%) and 74.6% (95% CI, 70%-79%) with type 1 and 13.9% (95% CI, 12%-16%) and 57.7% (95% CI, 54.6%-60.8%) with type 2 FLT3i. QTc prolongation occurred in 2.06% (95% CI, 1.03%-3.65%) with type 1 and 7% (95% CI, 5.3%-9%) with type 2 FLT3i. Type 2 FLT3i had less GI toxicity but more QTc prolongation. Prospective studies are needed to compare the efficacy of type 1 and 2 FLT3i.

Gemcitabine-induced digital ischaemia in a patient with metastatic breast cancer.

A woman in her 50s with HER2 (human epidermal growth factor receptor 2) positive, estrogen/progesterone receptor negative, metastatic invasive ductal carcinoma of the breast, presented with acral cyanosis and severe throbbing pain after recent administration of gemcitabine. She was treated with aspirin, heparin, amlodipine, topical nitroglycerin and analgesics. Gemcitabine was discontinued permanently. She had a gradual recovery except for a small necrotic area over the right 4th digit. However, surgical intervention was avoided.

Leiomyosarcoma of the Penis: A Case Report and Re-Appraisal.

Background: Penile leiomyosarcoma arises from smooth muscles, which can be from dartos fascia, erector pili in the skin covering the shaft, or from tunica media of the superficial vessels and cavernosa. We describe presentation, treatment options, and recurrence pattern of this rare malignancy. Case Presentation: We present a case of penile leiomyosarcoma in a 70-year-old patient who presented to the urology clinic with 1-year history of a slowly enlarging penile mass associated with phimosis. Conclusions: Prognosis of penile LMS is difficult to ascertain because reported cases are rare. Penile leiomyosarcoma can be classified as superficial or deep based on tumor relation to tunica albuginea. Deep tumors (> 3 cm), high-grade lesions, and tumors with involvement of corpora cavernosa, tend to spread locally and metastasize to distant areas and require more radical surgery with or without postoperative radiation therapy. In contrast, superficial lesions can be treated with local excision only.

Crime and punishment: Pakistan's legal failure to account for mental illness.

The Mental Health Ordinance 2001 was the last comprehensive legislation on mental health policy in Pakistan, replacing the Lunacy Act 1912. Since then, most of the amendments to the act have only delineated the jurisdiction of the provincial governments. Failure to account for mental illness in Pakistan brings with it unique challenges, such as the criminalisation of suicide and exploitation of blasphemy laws. There is a need for organised efforts to promote awareness of mental illness, amend the obsolete legislation in conformity with the scientific evidence, implement mental health policy effectively and deal with sensitive issues that have a strong sociocultural or religious background.

Leiomyosarcoma of the Tracheostomy Site in a Patient with History of Laryngeal Squamous Cell Carcinoma.

Leiomyosarcoma (LMS) of the trachea is an extremely rare malignancy with only a few reported cases in English literature. As such the diagnosis can be frequently missed or delayed. We present a case of a 69-year-old male who underwent tracheostomy for airway obstruction secondary to glottic squamous cell carcinoma and treated definitely with radiation therapy. Subsequently, the patient developed LMS of the tracheostomy site. The case further details multiple risk factors that could contribute to development of LMS including radiation exposure, prior malignancy, and chronic inflammation. These risk factors have been well established for LMS in other sites but less so in the head and neck region, which is the subject of our discussion. We also review the current guidelines for head and neck as well as limb sarcomas and discussed role of surgery or radiation and their accompanying challenges in management of this rare malignancy.

Concurrent Diagnosis of Acute Myeloid Leukemia and COVID-19: A Management Challenge.

The emergence of coronavirus disease 2019 (COVID-19) has created new challenges in the management of serious diseases. We describe a 41-year-old male who presented with fever, watery diarrhea, and epistaxis. Initial workup revealed pancytopenia with >50% blasts on the peripheral smear raising suspicion of acute myeloid leukemia (AML) (later confirmed by bone marrow biopsy as AML with myelodysplasia-related changes) and a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the extraordinary risk, he was treated with remdesivir and convalescent plasma for COVID-19. On admission day 8, repeat PCR for SARS-CoV-2 returned negative and the patient was deemed stable for chemotherapy. Therefore, induction was done with liposomal daunorubicin and cytarabine. However, he did not respond to the therapy and was started on re-induction therapy with decitabine and venetoclax. In our discussion, we review the current principles of treatment of patients with concurrent COVID-19 and AML.

Disseminated Histoplasmosis with Concurrent Hairy Cell Leukemia.

Histoplasmosis is an endemic fungal infection that can lead to disseminated disease, especially in immunosuppressed patients. Hairy cell leukemia is a rare, slow-growing hematological malignancy. Concurrence of histoplasmosis and hairy cell leukemia is extremely rare. We describe a 69-year-old male who presented with fever, dry cough, pancytopenia, multiple pulmonary nodules, and massive splenomegaly. Histoplasma urinary antigen was positive and disease was confirmed by biopsy of lung lesions. Peripheral smear showed 'hairy cells', and bone marrow biopsy revealed findings of hairy cell leukemia. The patient was treated with intravenous amphotericin, followed by oral itraconazole. After the initial treatment of infection, treatment for hairy cell leukemia was started with cladribine. We will discuss the principles of treating disseminated histoplasmosis in the setting of immunosuppression, and hairy cell leukemia with coexisting infection.

Hemorrhagic Cystitis Secondary to Adenovirus and BK Virus Infection in a Diffuse Large B-Cell Lymphoma Patient with Recent CAR T-Cell Therapy.

Patients who undergo chimeric antigen receptor T-cell therapy (CAR T-cell therapy) are immunosuppressed due to multiple factors. While adenovirus and BK virus are well-known pathogens in the context of hematopoietic stem cell transplant, there are no detailed reports of these infections in the setting of CAR T-cell therapy. We describe a 70-year-old male who recently underwent CAR T-cell therapy for diffuse large B-cell lymphoma. He presented with intractable gross hematuria and dysuria. Workup revealed adenovirus viremia and viruria and BK virus viruria. He was treated for adenovirus hemorrhagic cystitis with intravenous cidofovir 1 mg/kg/day, every three days for three weeks, with good clinical response. We also discuss the mechanisms of immunosuppression in CAR T-cell therapy as well as the principles of treatment of adenovirus and BK virus infections in the immunosuppressed patient.

Acute Myeloid Leukemia with Philadelphia Chromosome, Near-tetraploidy, and 5q Deletion.

A 49-year-old male presented to his physician with three weeks of dyspnea, dry cough, and fever. He did not respond to antibiotics and corticosteroids. He presented to the emergency department with worsening symptoms, where blood work revealed severe anemia, leukocytosis, thrombocytopenia, and 61% blasts on peripheral smear. Bone marrow biopsy showed acute myeloid leukemia (AML). While the results of other studies were awaited, treatment was begun with 7+3 induction (cytarabine and daunorubicin). Karyotyping returned positive for the BCR-ABL1 fusion gene (Philadelphia chromosome), near-tetraploidy, and 5q deletion. Follow-up bone marrow biopsy revealed residual disease (12% blasts). Re-induction was initiated with 5+2 cytarabine and daunorubicin with the addition of dasatinib. Subsequent bone marrow biopsies revealed minimal residual disease and BCR-ABL on polymerase chain reaction (PCR). The patient was placed on dasatinib maintenance and later switched to nilotinib. This case demonstrates the simultaneous presence of rare cytogenetic abnormalities in AML. It also discusses the successful utilization of tyrosine kinase inhibitors (TKIs) in the treatment of BCR-ABL-positive AML, as there are no established guidelines.

Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare haematological malignancy defined by concurrent expression of CD4, CD56, BCL-2 and CD123. The disease has a very poor prognosis and there are no well-established treatment guidelines. We describe a case of BPDCN in a 65-year-old female patient with myeloproliferative disorder (essential thrombocythemia) and chronic lymphocytic leukaemia. She presented with rapidly progressive facial and scalp lesions. Skin biopsy confirmed BPDCN and the imaging revealed widespread disease. Patient was started on hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) and intrathecal methotrexate. Due to progression on initial treatment, she was treated with decitabine and venetoclax (BCL-2 inhibitor). However, patient continued to deteriorate and died after 4 months from initial diagnosis. We emphasise on the clinical features, emerging treatment modalities and prognosis of BPDCN.

Cardiac tamponade in a patient with stage IV lung adenocarcinoma treated with pembrolizumab.

Immunotherapy drugs are associated with a multitude of immune-related adverse events. We describe a case of cardiac tamponade in a patient with stage IV lung adenocarcinoma, with almost 100% expression of PDL-1, treated with pembrolizumab. The patient is a 62-year-old male who developed worsening shortness of breath after five cycles of pembrolizumab. He was diagnosed with large pericardial effusion on computed tomography chest. Echocardiogram confirmed tamponade physiology. He was treated with discontinuation of pembrolizumab and urgent pericardial window followed by high dose prednisone with tapering. The patient responded very well to the treatment. We have comprehensively reviewed cases of pericardial effusion secondary to either immune mediated mechanisms or pseudoprogression.