Extrapulmonary Sites Research Articles

Incidental Primary Cystic Duct Lymph Node Tuberculosis in a 28-year-old Female: A Rare Case Report

Tuberculosis (TB) is an infectious disease caused by acid-fast bacilli Mycobacterium tuberculosis (MTB). The lung remains the most common site involved by it. Extrapulmonary sites of TB are lymph nodes, pleura, bone, joints, urogenital tract, and meninges. Isolated Cystic Duct Tubercular Lymphadenitis (CDL TB) without involving the gallbladder is an uncommon manifestation of TB that primarily affects the lymph nodes around the cystic duct. A multidisciplinary approach is essential for accurate diagnosis and successful management of such cases. The authors hereby present a case of a 28-year-old female, without any evidence of TB elsewhere and an incidental finding of CDL TB. “The patient was sent with a clinical diagnosis of Chronic Calculus Cholecystitis (CCC)”. This highlights the need for comprehensive clinical evaluation and diagnostic investigations to avoid misdiagnosis or delayed management. This underscores the significance of maintaining a high index of suspicion for extrapulmonary TB, particularly in regions where the disease remains endemic. Healthcare practitioners should be vigilant when encountering unusual clinical presentations or when dealing with atypical combinations of gallbladder pathologies, as illustrated by the concurrent occurrence of CDL TB with CC with evidence of Pyloric Metaplasia (PM) and cholesterolosis without cholelithiasis, as in the patient of the present case report.

Disseminated Tuberculosis: A 6-year Case Series Experience in a Tertiary Care Center.

Disseminated tuberculosis (dTB) disease is associated with a significant burden of morbidity and mortality and it requires improved awareness among clinicians. Case reports revealing the clinical and microbiological characteristics of dTB patients will help us to extend our knowledge of dTB. In our study, we have documented dTB cases followed for 6 years and revealed patients' clinical characteristics. Patients followed between 2017 and 2023 who were diagnosed with dTB in a tertiary referral hospital in Istanbul have been evaluated. Data regarding patients' characteristics, methods used in establishing the definitive diagnosis, radiological patterns in chest X-rays, extrapulmonary sites involved, antituberculosis (TB) treatment regimens received, medication side effects, and drug resistance have been examined. Descriptive statistics were performed. Clinical characteristics of 55 patients with a median age of 41 (range 20-85, 52.7% male) were examined. The most common extrapulmonary involvements in our study were the skeletal system (n = 24), central nervous system (n = 7), and genitourinary tract (n = 7). Isoniazid (INH) resistance was detected in four patients. Mono resistance was reported for pyrazinamide in one patient. Multidrug resistance was detected in two patients and one of them was also resistant to ethambutol. Preextensively, drug resistance was reported in three patients. Another three patients were evaluated as resistant to both INH and streptomycin. Migrating from a high TB burden country and comorbidities such as diabetes mellitus, human immunodeficiency virus, and rheumatoid arthritis that are related to immunocompromisation are thought to be risk factors for dTB.

Imaging of thoracic tuberculosis: pulmonary and extrapulmonary.

Tuberculosis (TB) remains the leading cause of death from a single infectious agent globally, despite being a potentially curable disease. This disease typically affects the lungs but may involve many extrapulmonary sites, especially in patients with risk factors such as HIV infection. The clinical features of extrapulmonary TB may mimic many different disease entities, particularly at less common thoracic sites such as the heart, chest wall, and breast. Imaging has an important role in the early diagnosis of TB, helping to detect disease, guide appropriate laboratory investigation, demonstrate complications, and monitor disease progress and response to treatment. Imaging supports the clinical objective of achieving effective treatment outcome and complication prevention. This review aims to highlight the imaging spectrum of TB affecting both pulmonary and extrapulmonary sites in the thorax. We also briefly provide key background information about TB, such as epidemiology, pathogenesis, and diagnosis.

Finger-Prick Whole Blood Cryptococcal Antigen Lateral Flow Assay for the Diagnosis of Cryptococcosis in HIV-Negative Patients: A Case Series Study in Two Tertiary Centers in São Paulo, Brazil.

Cryptococcosis in HIV-negative patients can be an opportunistic or endemic disease. There are no published studies on the use of the finger-prick whole blood (point-of-care) cryptococcal antigen lateral flow assay (CrAg LFA) for diagnosing cryptococcosis in HIV-negative patients. We conducted a case series study of HIV-negative patients with cryptococcosis in two centers in São Paulo, Brazil. The objectives were to identify the sensitivity of a finger-prick whole blood CrAg LFA and to describe the main characteristics of this population. We identified 30 HIV-negative patients with cryptococcosis [19 (63%), male; median age, 47 years]. Ten (33%) patients were immunosuppressed, ten (33%) had other comorbidities, and ten (33%) were apparently immunocompetent and without comorbidities. The distribution of the sites of cryptococcosis was as follows: the central nervous system, 90% (n = 27); pulmonary, 43% (n = 13); and other extrapulmonary sites, 40% (n = 12). The sensitivity of the finger-prick whole blood CrAg LFA for the diagnosis of cryptococcosis was 97% (29/30). Among 26 participants with cryptococcal meningitis, the sensitivity of testing cerebrospinal fluid was as follows: CrAg latex agglutination, 77% (20/26); CrAg LFA, 96% (25/26); and culture, 81% (21/26). Culture speciation identified Cryptococcus gattii in 16 (62%) cases, and all had a positive finger-prick whole blood CrAg LFA. This test presented high sensitivity to the diagnosis of cryptococcosis in HIV-negative patients, including those caused by C. gattii.

Unusual tongue metastasis from lung adenocarcinoma in a cat with feline lung–digit syndrome

This report describes the pathological findings in a 15-year-old spayed female Domestic Shorthaired cat with a pulmonary adenocarcinoma characterized by feline lung–digit syndrome (FLDS) and unusual tongue metastasis. Felis catus papillomavirus type 3 (FcaPV-3) DNA was amplified from the lingual sample but not from samples of the pulmonary mass or digital or splenic metastatic lesions, indicating the presence of FcaPV-3 in the oral cavity but not suggesting a role for FcaPVs in tumour pathogenesis. FLDS is a clinical entity in which primary lung tumours present because of metastatic digital lesions. In humans, tongue metastasis may be a rare initial presentation of lung cancer, whereas, to the best of our knowledge, tongue metastasis of feline tumours has not been reported. Although lingual metastases are rare, the present findings serve to remind clinicians that metastatic manifestations of primary lung tumours in cats may involve multiple extrapulmonary sites, including the tongue.

Multifocal Tuberculosis in Immunocompetent Children, Still A Current Problem: About 13 Cases

Multifocal tuberculosis corresponds to involvement of at least two extra-pulmonary sites associated or not with pulmonary involvement. Material and Method: This is a retroprospective descriptive study of patients diagnosed with tuberculosis between 2018 and 2022, in the pediatric infectious diseases department at the Rabat children's hospital. Clinical, paraclinical, therapeutic and evolutionary data were collected on a pre-established information sheet. Results: 13 cases were collected in this study, the patients were all correctly vaccinated with BCG, with notion of tuberculosis contagion in 6 cases which were not screened, the localizations found in this series, pulmonary, peritoneal, spinal, cerebral, meningeal and lymph node, the evolution under treatment started early is favorable. Discussion: Multifocal tuberculosis poses a diagnostic problem given its clinical polymorphism, which causes delay in diagnosis. Several localizations are found, the most frequent being meningocerebral in this series and lymph node in the literature. A genetic predisposition to the disease has been suggested in immunocompetent patients.

Distribution and Rate of Myxoid Liposarcoma Spine Metastases: Impact on Surveillance Imaging.

Myxoid liposarcoma (LPS) has a unique tendency to spread to extrapulmonary sites, including osseous sites such as the spine, and adjacent sites such as the paraspinous tissue. No clear consensus exists to guide the approach to imaging in these patients. The aim of this study was to investigate the rate and distribution of spine metastases in patients with myxoid LPS and detection modality. Records of all patients with myxoid LPS evaluated at our sarcoma center were retrospectively reviewed. Disease patterns and imaging modality utilization were analyzed. Between 2000 and 2020, 164 patients with myxoid LPS were identified. The majority (n=148, 90%) presented with localized disease, with half (n=82, 50%) of all patients developing metastases or recurrence during their disease course. With a median follow-up of 69.2 months, spine/paraspinous metastases developed in 38 patients (23%), of whom 35 (92%) already had synchronous, non-spine metastases. Spine disease was only visible on magnetic resonance imaging (MRI), as opposed to other imaging modalities, for over one-quarter of patients with spine metastases (n=10). For patients with metastatic disease, spine metastases were associated with worse median overall survival (2.1 vs. 8.7 years, p<0.001). Spine metastases occurred in nearly one-quarter of patients with myxoid LPS and represented an advanced disease state, as they primarily presented in the setting of synchronous, non-spine metastases, and were associated with worse overall survival. Routine surveillance with spine MRI in patients with localized disease likely provides no benefit but may be considered in those with known metastatic disease.

A-288 Molecular Detection of Mycobacterium tuberculosis in Pulmonary and Extra-Pulmonary Samples. Data from a Brazilian Clinical Laboratory

Abstract Background Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is among the leading infectious causes of death in developing countries. In humans, TB presents as a progressive granulomatous infectious disease that affects lungs causing pulmonary tuberculosis, but can also affect intestines, meninges, bones, joints, lymph nodes, skin and other body tissues causing extra-pulmonary tuberculosis. The aim of this study was to evaluate the frequency of tuberculosis cases detected during the COVID-19 period and the emergence of cases with extrapulmonary diagnosis. Methods This study was a retrospective analysis from January 2017 to December 2022 based on the analysis of 3105 clinical samples processed by the molecular biology section of AFIP Laboratory. All clinical samples were isolated from pulmonary and extra-pulmonary sites recovered from inpatients admitted in several Brazilian tertiary hospitals. In Brief, the DNA extraction was performed according to the type of patient’s samples and, then submitted to Real-Time PCR (qPCR) method using a commercial kit, which contains specific primers and probes to the M. tuberculosis genome. Results Of the 3105 samples tested, 222 (14%) samples were positive for the presence of M. tuberculosis. Out of which, 120/1405 (8,5%) were detected in the pre-Covid-19 period (2017–2019) and 102/1700 (6%) were detected in Covid-19 period (2020–2022). The prevalence of M. tuberculosis infection was 64.5% and 35.5% among men and females, respectively. The main age range was 41 to 50 years (44.7%), while over 60 years comprised 13.5% of cases (Fig. 1). Between the isolate sites, 67.1% of the M. tuberculosis cases were detected in pulmonary and 32.8% in extra-pulmonary body sites, of which, cerebrospinal fluid and blood are among the most frequent, followed by cervical lymph node, ascitic fluid, gastric lavage, urine and others. A total of 95% of M. tuberculosis was detected in patients assisted by public health service. We did not have access to patient’s symptoms, clinical history or further diagnostic procedures. Conclusion Comparing the two periods of the study, a reduction in the positivity rate of new cases was observed in the pandemic period, perhaps this fact can be associated with restrictions on access to the diagnosis of other pathologies in the pandemic period. Despite no information about the severity of the infection, male gender prevalence and age range from 41 to 50 years group need further attention.

Whole genome sequencing of drug resistance Mycobacterium tuberculosis from extra-pulmonary sites.

This study aimed to determinate characteristics of drug resistance Mycobacterium tuberculosis from patients with extra-pulmonary tuberculosis (EPTB). Patients were retrospectively studied from January 2020 to December 2021. All the isolates were cultured, tested drug susceptibility, and detected the gene mutation using whole genome sequencing. The correlations of whole genome sequencing, pattern of DR, patients' distribution, and transmission were analyzed. 111 DR-EPTB isolates included pre-XDR-TB (53.2%), MDR-TB (29.7%), and poly-DR-TB (12.6%). The resistant drugs were INH followed by RFP and SM. The genotypes of 111 strains were lineage 2 and lineage 4. KatG_p.Ser315Thr was main gene mutation for resistance to INH; rpsL_p.Lys43Arg for SM, rpoB_p.Ser450Leu for rifampicin, embB_p.Met306Val for ethambutol, gyrA_p.Asp94Gly for FQs, and pncA_p.Thr76Pro for PZA. The residence was a significant risk factor for cluster transmission by patients and phenotypic DR types of strains for lineage 2 transmission. In the local area of southwest China INH, rifampicin and SM were main drugs in patients with DR-EPTB. KatG_p.Ser315, rpoB_p.Ser450Leu, and rpsL_p.Lys43Arg were main gene mutations. Phenotypic DR types and residence were main risk of transmission.

A physiologically-based pharmacokinetic model for tuberculosis drug disposition at extrapulmonary sites.

Tuberculosis (TB) is a leading cause of mortality attributed to an infectious agent. TB primarily targets the lungs, but in about 16% cases can affect other organs as well, giving rise to extrapulmonary TB (EPTB). However, an optimal regimen for EPTB treatment is not defined. Although the recommended treatment for most forms of EPTB is the same as pulmonary TB, the pharmacokinetics of EPTB therapy are not as well studied. To address this gap, we formulate a whole-body physiologically-based pharmacokinetic (PBPK) model for EPTB that for the first time includes the ability to simulate drug concentrations in the pleura and lymph node, the most commonly affected sites of EPTB. Using this model, we estimate the time-dependent concentrations, at potential EPTB infection sites, of the following four first-line anti-TB drugs: rifampicin, ethambutol, isoniazid, and pyrazinamide. We use reported plasma concentration kinetics data to estimate model parameters for each drug and validate our model using reported concentration data not used for model formulation or parameter estimation. Model predictions match the validation data, and reported pharmacokinetic parameters (maximum plasma concentration, time to reach maximum concentration) for the drugs. The model also predicts ethambutol, isoniazid, and pyrazinamide concentrations in the pleura that match reported experimental values from an independent study. For each drug, the predicted drug concentrations at EPTB sites are compared with their critical concentration. Simulations suggest that although rifampicin and isoniazid concentrations are greater than critical concentration values at most EPTB sites, the concentrations of ethambutol and pyrazinamide are lower than their critical concentrations at most EPTB sites.

Extrapulmonary Tuberculosis: A Retrospective Study in Eastern India Based on Diagnostic Modalities

Background: The most common site of tubercular infection is lungs, but various extrapulmonary sites also can be affected by tuberculosis (TB). Very few fine-needle aspiration-based studies supplemented by cartridge-based nucleic acid amplification test (CBNAAT) and radiology have been conducted in any center of tribal-based area situated in Eastern India. Materials and Methods: Sixty extrapulmonary TB cases (28 males and 32 females) received during 3 years (May 2018–April 2021) were included in this study. Results: Diagnoses of different extrapulmonary tubercular lesions were: lymphadenitis (n = 27), cold abscess (n = 18), breast abscess (n = 2), epididymitis (n = 4), oral cavity (n = 3), spine, long bone (n = 2 cases each) and fingertip and TB of the penis (n = 1 case each). Forty-six cases were diagnosed by fine-needle aspiration cytology. CBNAAT diagnosed ten cases where the result of aspiration cytology was inconclusive. Radiology directly diagnosed four cases, whereas it helped another seven cases indirectly to clinch the proper diagnosis of extrapulmonary tubercular lesions. Conclusion: Tuberculous lymphadenitis was the most common extrapulmonary lesion. Females outnumber male cases. Aspiration cytology aided by CBNAAT and radiology proved indispensable to diagnose extrapulmonary tubercular lesions, especially for economically constrained persons.

Imaging Findings in Aspergillosis: From Head to Toe.

Aspergillosis is a mycotic infection induced by airborne fungi that are ubiquitous. Inhalation of Aspergillus conidia results in transmission through the respiratory tract. The clinical presentation is dependent on organism and host specifics, with immunodeficiency, allergies, and preexisting pulmonary disease constituting the most important risk factors. In recent decades, the incidence of fungal infections has increased dramatically, due in part to the increased number of transplants and the pervasive use of chemotherapy and immunosuppressive drugs. The spectrum of clinical manifestations can range from an asymptomatic or mild infection to a swiftly progressive, life-threatening illness. Additionally, invasive infections can migrate to extrapulmonary sites, causing infections in distant organs. Recognition and familiarity with the various radiological findings in the appropriate clinical context are essential for patient management and the prompt initiation of life-saving treatment. We discuss the radiological characteristics of chronic and invasive pulmonary aspergillosis, as well as some of the typically unexpected extrapulmonary manifestations of disseminated disease.

Prevalence of tuberculosis in Hadramout Al-Sahel, Yemen: A 1-year cross-sectional study

Background: There is a lack of adequate data about the prevalence and types of tuberculosis (TB) disease in Hadramout Al-Sahel, Yemen. Hence, this study aimed to investigate the prevalence, types, and outcomes of TB disease in Hadramout Al-Sahel, Yemen. Materials and Methods: This cross-sectional study was conducted at the National TB Program (NTP) center in the city of Al Mukalla, Hadramout, Yemen. The study enrolled TB patients from different districts of Hadramout Al-Sahel who had registered at the NTP center between January 1 and December 31, 2021. Results: A total of 127 new active TB cases were recruited, including 102 (80.3%) with pulmonary TB (PTB) and 25 (19.7%) with extra PTB (EPTB). The overall prevalence of TB disease in 2021 was 12.7 new TB cases per 100,000 population, while the median age of the study population was 38 years. The majority of cases (23.6%) belonged to the age group of 35–44 years. There were 85 (66.9%) males, and most patients (74; 58.3%) were identified in Al Mukalla City. EPTB was detected in 25 (19.7%) patients, with pleural effusion being the most frequent manifestation, found in 12 (48.0%) patients. All patients received 4-agent anti-TB therapies; 99 (77.9%) patients received anti-TB therapy for 6 months; 9 (7.1%) patients received anti-TB therapy for 9–12 months; 8 (6.3%) patients died during treatment; and 11 (8.7%) patients were lost during follow-up. The majority of patients (108; 85%) were cured on completion of treatment. Conclusion: The prevalence of TB in Hadramout Al -Sahel was 12.7 cases per 100,000 population. Males were affected more than females; the pleura was the most commonly affected extrapulmonary site; and 85% of cases were cured. The results indicated the need to support the Al Mukalla NTP center, by providing more resources for improved TB reporting and for conduct of surveillance to detect new TB cases among high-risk groups. Health authorities are also urged to provide state hospitals with the equipment needed for TB diagnosis.

Rhabdomyosarcoma with isolated lung metastases: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

To determine outcomes of children with rhabdomyosarcoma (RMS) with isolated lung metastases. Data were analyzed for 428 patients with metastatic RMS treated on COG protocols. Categorical variables were compared using Chi-square or Fisher's exact tests. Event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier method and compared using the log-rank test. Compared with patients with other metastatic sites (n=373), patients with lung-only metastases (n=55) were more likely to be <10 years of age, have embryonal histology (embryonal rhabdomyosarcoma), have N0 disease, and less likely to have primary extremity tumors. Lung-only patients had significantly better survival outcomes than patients with all other sites of metastatic disease (p<.0001) with 5-year EFS of 48.1 versus 18.8% and 5-year OS of 64.1 versus 26.9%. Patients with lung-only metastases, and those with a single extrapulmonary site of metastasis, had better survival compared with patients with two or more sites of metastatic disease (p<.0001). In patients with ERMS and lung-only metastases, there was no significant difference in survival between patients ≥10 years and 1-9 years (5-year EFS: 58.3 vs. 68.2%, 5-year OS: 66.7 vs. 67.7%). With aggressive treatment, patients with ERMS and lung-only metastatic disease have superior EFS and OS compared with patients with other sites of metastatic disease, even when older than 10 years of age. Consideration should be given to including patients ≥10 years with ERMS and lung-only metastases in the same group as those <10 years in future risk stratification algorithms.

Multifocal Tuberculosis in a Diabetic: An Atypical Manifestation

Introduction: Multi-focal tuberculosis is an attack of two extra-pulmonary sites with or without pulmonary involvement. It is a rare pathology that is characterized by its large clinical and radiological polymorphism. We report the case of a 27-year-old patient with type 1 diabetes, who had had a stroke for 1 year. She reported the appearance of a sushyphoidal collection for a month. The clinical examination noted a sus-xyphoid collection firm edge and renit in its center of 5cm in diameter painless evoking a cold abscess. Examinations had shown poorly systematized opacity at the level of the right lung base on chest radiography, with the ultrasound of the upper xyphoidal region showing abscess collected supersternal with discontinuous sternal cortices, suggesting bone lysis. The CT scan confirmed the appearance of sternal osteitis with collections of the soft tissues opposite, multiple associated hepatic collections were objectified at the level of the abdominal sections with pulmonary involvement of infectious origin objectified to the thoracic sections. the puncture of the abscess had not found AFB. The diagnosis of multifocal tuberculosis was retained following a positive expert Gen test. Management consisted of anti- bacillary therapy, adjustment of insulin doses. The appearance of multi-focal tuberculosis is often misleading and can mislead the diagnosis. However, the essential thing is to know how to evoke them in order to be able to target the specific examinations and to engage the therapeutic strategy without delay. Our case illustrates an atypical manifestation of multifocal tuberculosis in a diabetic patient with pulmonary, cutaneous, hepatic and bone lesions of tuberculosis origin.

Comparative study between CBNAAT and acid-fast bacilli culture in extra pulmonary tuberculosis

Introduction: Mycobacterium Tuberculosis is a complex organism in which lungs are the main portal of infection. Tuberculosis affecting organs other than lungs called as extrapulmonary tuberculosis. Tuberculous lymphadenitis is the most common form of Extrapulmonary Tuberculosis contributing to 35 percent of Extrapulmonary Tuberculosis cases. CBNAAT is a cartridge based nucleic acid amplification test which detects the presence of Mycobacterium Tuberculosis as well as Rifampicin resistance. Materials and Methodology: Samples were collected from the appropriate extrapulmonary sites which included Lymph Node aspirate, Pleural fluid, Ascitic fluid, Abscess, Cerebrospinal Fluid. The samples were sent for AFB smear, CBNAAT and AFB culture. The data was analyzed and results were compared. Results: This cross-sectional study was conducted in a sample size of 89 patients attending the outpatient department in a tertiary care center in the Department of Respiratory Medicine at Santosh Hospital, Ghaziabad who were clinically suspected cases of Extra Pulmonary Tuberculosis. MTB was detected in CBNAAT in 33(37%) cases giving a Yield of 37% with RIF resistance in 2(2.2%) cases and MTB was detected in 53(59.5%) giving it a yield of 59.5% with RIF resistance in 2. Conclusion: There was statistically significant weak agreement seen between CBNAAT finding and AFB culture finding (Kappa value = 0.48; p value &lt;0.01).

Phase 1/2 trial of vesicular stomatitis virus expressing human interferon-β and NIS (VSV-IFNβ-NIS), with pembrolizumab, in patients with neuroendocrine carcinoma.

TPS657 Background: Poorly differentiated neuroendocrine carcinoma (NEC) is an aggressive malignancy comprising both pulmonary and extrapulmonary primary sites. NEC includes both small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), as well as other neuroendocrine carcinomas arising from any primary organ. A substantial portion (~40%) of NEC arises from gastrointestinal primary sites. The optimal systemic therapy beyond first line platinum and etoposide is not established. There is a critical need to improve upon the median survival in the second line, as most patients do not survive more than 6 months. The efficacy of single agent immune checkpoint inhibitors (ICIs) in NEC has been disappointing. One possible explanation for this is that the tumor microenvironment in NEC is non-inflamed. VSV-IFNβ-NIS is a vesicular stomatitis virus (VSV)-based oncolytic virus being tested in multiple early phase clinical trials. Preliminary studies of immune responses in patients receiving VSV-IFNβ-NIS therapy suggest some patients develop T cell responses to viral antigens and known tumor antigens. We hypothesize that VSV-IFNβ-NIS therapy may convert a non-inflamed or immune-excluded phenotype in NEC to a highly inflamed phenotype that sensitizes the tumor to ICIs. Methods: This is a phase 1-2 safety run-in study designed to determine the safety of VSV-IFNβ-NIS in combination with a single agent ICI, pembrolizumab, followed by dose expansion in patients with refractory non-small cell lung cancer (NSCLC) or NEC. The safety run-in portion of this study has been completed, and we are presently testing the recommended phase 2 dose (RP2D) of VSV-IFNβ-NIS in an expansion cohort of patients with SCLC or NEC of any primary site. Patients must have previously progressed on at least one line of systemic therapy. Prior treatment with checkpoint inhibitors is permitted. Patients are treated one time with the RP2D of 1.0x10^11 TCID50 VSV-IFNβ-NIS on day 1, followed by pembrolizumab on day 8 and then pembrolizumab every 21 days until progression, up to 2 years. The primary objective is to estimate the response rate by RECIST 1.1. Secondary objectives include estimation of disease-control rate, duration or response, progression-free survival, overall survival, and safety signals. The NEC expansion cohort will seek to enroll 10 patients. If at least one objective response is observed, and safety is confirmed, the regimen will be considered for future study. Clinical trial information: NCT03647163 .

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas.

The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a significant number of reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although the mechanisms of GI pathogenesis are still being examined, viral components isolated from stool samples of infected patients suggest a potential fecal-oral transmission route. In addition, viral RNA has been detected in blood samples of infected patients, making hematologic dissemination of the virus a proposed route for GI involvement. Angiotensin-converting enzyme 2 (ACE2) receptors serve as the cellular entry mechanism for the virus, and these receptors are particularly abundant throughout the GI tract, making the intestine, liver, and pancreas potential extrapulmonary sites for infection and reservoirs sites for developing mutations and new variants that contribute to the uncontrolled spread of the disease and resistance to treatments. This transmission mechanism and the dysregulation of the immune system play a significant role in the profound inflammatory and coagulative cascades that contribute to the increased severity and risk of death in several COVID-19 patients. This article reviews various potential mechanisms of gastrointestinal, liver, and pancreatic injury.

Small Cell Neuroendocrine Carcinoma in the Maxillary Sinis Region

Small cell neuroendocrine carcinoma (SCNC) is an undifferentiated neoplasm that occurs primarily in the lungs. However, although extremely rare, it can also manifest in a variety of extrapulmonary sites, some of the most common being: prostate, urinary bladder, stomach, esophagus, salivary glands, larynx, gallbladder, skin and cervix. It is believed that these tumors develop from totipotent stem cells, which are present in all tissues. Furthermore, it can manifest as a metastatic disease from an unidentified primary site, with the head and neck region being the 4th most common site of extrapulmonary origin (16%)1. Extrapulmonary SCNC is histopathologically similar to those of the pulmonary site, and also has an aggressive biological behavior, marked by local recurrences and the early occurrence of distant metastases (especially to regional lymph nodes, bones and liver), with a 5-year survival rate of around 15%.1 In general, the initial symptoms are due to locoregional disease, but are indistinguishable from other tumors at the same site; symptoms can also be manifested by paraneoplastic syndromes and signs of distant metastasis. The approach varies according to the site of localization, presence of metastases and extent, however, treatment is generally performed surgically and/or through chemotherapy (usually containing etopside and platinum compounds) and radiotherapy, and aggressive locoregional therapy can be used in cases of localized disease, however, recurrences are common and adjuvant chemotherapy is

Tuberculosis of Bones and Joints in Orthopedic

Background: Mycobacterium Tuberculosis (TB) is a major global health concern and burden on developing countries economy. Pakistan ranks in top 10 countries of the world with high load of TB and a big chunk of this disease process is extra pulmonary TB (EPTB). Among extra pulmonary sites, is bone and joint TB is very common yet under reported. Recent literature has found up to 35% of all extra pulmonary cases are bone and joint TB. Purpose: We aim to do an analysis of frequency of bone and joint TB in our institution in all new patients getting registered for treatment of TB. Methodology: This was retrospective analysis 8 years of Data collected in Gulab Devi Hospital Lahore. Data was analyzed using Microsoft excel software and results are tabulated. Findings: Total number of new registered patients of Extra-pulmonary Tuberculosis (EPTB) were 13000 (20%). Out of these EPTB patients, bone and joint TB diagnosis was made in 690(5.3%) patients. Out of these 690 patients, 400 (58%) cases were recorded in Indoor facility and 290 (42%) cases were seen in outdoor facility. Most common site is Spine 340 cases (85%) followed by Hip joint 16 cases (4%), knee joint 12 cases (3%) and upper limb 16 cases (4%). Practical Implication: Regarding management of newly registered cases, Gulab Devi hospital is working in collaboration with world Health Organization TB control program and Provincial TB control Program Punjab (PTP). All new cases are managed by multi-disciplinary team and after initial registration are referred to their relevant specialties. Conclusion: Axial skeleton remains the most common site in al literature and so is the conclusion of our analysis. Detailed research work is still needed in several aspects of this ancient disease to reduce the morbidity and mortality associated with it. Keywords: Bone and joint TB, Pulmonary Tuberculosis, Extra pulmonary Tuberculosis