Patterns and predictors of periodontal disease and tooth loss among users of smokeless tobacco.

BACKGROUND: Smokeless tobacco (SLT) products of several different types are widely used in several South Asian countries including Pakistan. These products are consumed in different forms and with different names. The study aims to determine adverse effects of the SLT consumption on periodontal tissues. METHODS: This cross sectional study was conducted in Karachi, Pakistan. It recruited 377 users of (SLT) with 231 males (61.3%) and 146 females (38.7%) of age 15 to 45 years. After obtaining informed consent, quantitative data were collected via a questionnaire followed by intra oral clinical examination to determine presence of periodontal diseases using community periodontal index (CPI). To determine the association between periodontal diseases and smokeless tobacco consumption habits, Chi Square test was conducted. RESULTS: Gingival recession (Class II-IV) (65.8%) was the most prevalent periodontal disease among SLT users. CPI score was high (CPI score 3 and 4) in 31.3% participants, whereas tooth loss was found in 21%. Among types of SLT products, gutka (28.6%) and betel quid (23.3%) were most commonly used. Using SLT for five or more years was found to be associated with a high CPI score, gingival recession (Class II-IV), moderate to severe tooth mobility, and presence of tooth loss. CONCLUSIONS: The study found statistically significant association between duration in years of using SLT and periodontal disease including gingival recession, tooth mobility and tooth loss. However, no significant results were found between retention during single use and frequency of SLT use per day. However, the link of these factors with the periodontal disease cannot be eliminated.

Time for culture conversion and its associated factors in multidrug-resistant tuberculosis patients at a tertiary level hospital in Peshawar, Pakistan.

Objectives: This study aimed to assess the time to sputum culture conversion (SCC) and its determinants among multidrug-resistant tuberculosis (MDR-TB) patients. Methods: This cross-sectional study was conducted from January 2019 to January 2020. A total of 252 MDR-TB patients presenting at a tertiary level teaching hospital in Peshawar, Khyber Pakhtunkhwa (KP), were included. The patient's demographic and clinical data were collected using a structured questionnaire. Time to SCC was calculated from the initiation of treatment till the patient had two consecutive negative cultures. The Cox proportional-hazards analysis was performed to check strength and association between the determinants and time for SCC. Results: Out of 252 MDR-TB patients enrolled, sputum culture conversion was observed in 76.6% of the patients by the end of six months. While, 19.0% of the patients failed to achieve negative culture and remained positive after interim report of their treatment. Age > 45 years (HR = 15.22; 95% CI: 7.27-31.83; p<0.001), female gender (6.22; 2.90-13.36; p<0.001), BMI < 18.5 kg/m2 (10.28; 5.25-20.11; p<0.001), weight loss (0.03; 0.01-0.06; p<0.001), smoking (0.10; 0.05-0.21; p<0.001), diabetes mellitus (0.02; 0.00-0.04 p<0.001) and disease severity on chest X-ray (CXR) (0.03; 0.01-0.09; p<0.001) were the significant determinants of delayed sputum culture conversion. Conclusion: MDR-TB patients with older age, low BMI, weight loss, diabetes, smokers and those with disease severity on CXR are less likely to respond to treatment as they displayed delayed SCC. Therefore, such patients should be meticulously followed up for successful management.

Real-world evaluation of effectiveness and tolerance of chemotherapy for early-stage breast cancer in older women.

PURPOSE: Older patients with early-stage breast cancer (ESBC) tend to receive less aggressive treatment, have higher mortality rates, and are underrepresented in clinical trials. Outcomes, tolerance and toxicity of chemotherapy are underreported. Thus, we assessed the outcomes of chemotherapy in the real-world in a community oncology setting. METHODS: We retrospectively chart reviewed consecutive older patients (≥ 70 years) with ESBC diagnosed between January 1, 2010, and December 31, 2016, who received chemotherapy at our institution. Study outcomes were survival estimates. Logistic regression determined associations with measures of intolerance. RESULTS: Of 1296 patients, 229 received chemotherapy. Overall, 24% had early chemotherapy cessation; 18% had dose reductions; and 27% had dose delays. Severe, life threatening and lethal toxicities occurred in 38%, 1.3%, and 2.2%, respectively; constitutional toxicity (37%) was the most common. The 1- and 3-year overall survivals were 94% and 79%; 1- and 3-year breast-specific survivals were 96% and 89%, while 1- and 3-year disease-free survivals were 95% and 82%, respectively. Anthracyclines were the most poorly tolerated regimen having associations with hospital visits (OR 10.97, 95% CI 2.10-57.23) and severe toxicities (OR 5.28, 95% CI 1.27-21.89). Anti-HER2 therapies (OR 3.03, 95% CI 1.18-7.78) and poorer performance status (PS) (OR 7.48, 95% CI 1.75-31.98) were associated with severe toxicities. Older age (> 80 years) was associated with early cessation of therapy (OR 3.64, 95% CI 1.34-9.83). CONCLUSIONS: Chemotherapy can be effectively delivered to older patients with ESBC and is reasonably well tolerated. The high rate of anthracycline intolerability, poorer PS, and advanced age should be considered when tailoring treatment regimens.

Recent Advances in Preventing Chemotherapy-Induced Nausea and Vomiting.

Chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of cancer therapy. The goal of CINV prophylaxis is to reduce the morbidity associated with nausea and vomiting, as well as to preserve quality of life, while maintaining the desired chemotherapy regimen. The US Food and Drug Administration has recently approved new therapies for prevention of CINV, including the neurokinin-1 (NK1) receptor antagonist rolapitant and the fixed-dose combination of the second-generation 5-hydroxytryptamine type 3 receptor antagonist palonosetron with the novel NK1 receptor antagonist netupitant. Alternative agents, like the atypical antipsychotic olanzapine, have also expanded the options available for preventing delayed and refractory CINV. Consensus guidelines for prevention of CINV from several organizations are generally consistent with one another and are updated based on expert review of available clinical trial data. This article will address changes in CINV guidelines over the past 5 years and provide updates on recently approved agents and agents that are expected to be approved, based on published phase III trials. It will also explore other factors affecting optimal CINV control, including the role of patient-related risk factors and the role of physician adherence to antiemetic guidelines in reducing the residual risk of CINV.

Successful treatment of radiation-induced proctitis pain by blockade of the ganglion impar in an elderly patient with prostate cancer: a case report.

OBJECTIVE: Chronic rectal pain secondary to radiation-induced proctitis is fast-becoming a leading cause of chronic pain, especially for prostate cancer survivors. Currently, many elderly patients resort to increased opioid intake to alleviate the pain. However, this increase in opioid consumption often leads to constipation and further aggravates the anorectal pain, thus leading to a perpetual, vicious cycle. We reasoned that blocking the ganglion impar could attenuate this sympathetically maintained pain, which would lead to a reduction in the consumption of opioids, lessen constipation, and lead to an improvement in the patient's quality of life. STUDY DESIGN: Case report. SETTING: An academic tertiary pain management clinic. RESULTS: The authors report the case of a 73-year-old African American man with a history of prostate cancer who presented to the pain management clinic for evaluation and treatment of his chronic anorectal pain secondary to radiation-induced proctitis. The patient underwent a ganglion impar block, using the transcoccygeal technique, and consequently reported excellent pain relief with little or no use for opioid pain medications at a 2-month follow-up. Ultimately, this approach led to improved mobility and an increase in the patient's quality of life. CONCLUSIONS: Based on this case's success, a prospective study or randomized control trial evaluating the efficacy of the ganglion impar block as a treatment option for chronic anorectal pain secondary to radiation-induced proctitis appears warranted.

Coronavirus Does It Again: Post-COVID-19 Hemophagocytic Lymphohistiocytosis (HLH).

Hemophagocytic lymphohistiocytosis (HLH) is a hematological disorder that results from an uncontrolled activation of the immune system, which can then lead to multisystem organ failure. Given the nonspecific nature of this illness, it can go undetected for too long, thereby causing permanent damage to organ systems. In adults, HLH has been associated with a number of infectious etiologies, particularly viral infections. Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic and has been associated with acute respiratory distress syndrome (ARDS). Among its other manifestations, COVID-19 has also been linked to HLH. In this report, we describe a case of a male patient who presented with multisystem organ failure and was found to have HLH. Since no clear etiology for his HLH could be elicited, it was determined to be a result of his recent COVID-19 infection.

Burden of bone disease in chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND: Bone disease is an under-recognized cause of morbidity in chronic pancreatitis (CP). Over the past decade, publications of original studies on bone disease in CP has warranted synthesis of the evidence to ascertain the true burden of the problem. AIM: To quantify the prevalence of osteopenia, osteoporosis, and fragility fractures in CP patients and investigate the associated clinical features and outcomes. METHODS: A systematic search identified studies investigating bone disease in CP patients from Cochrane Library, Embase, Google Scholar, Ovid Medline, PubMed, Scopus, and Web of Science, from inception until October 2022. The outcomes included prevalence of osteopenia, osteoporosis, and fragility fractures, which were meta-analyzed using a random-effects model and underwent metaregression to delineate association with baseline clinical features. RESULTS: Twenty-one studies were included for systematic review and 18 studies were included for meta-analysis. The pooled prevalence of osteopenia and osteoporosis in CP patients was 41.2% (95%CI: 35.2%-47.3%) and 20.9% (95%CI: 14.9%-27.6%), respectively. The pooled prevalence of fragility fractures described among CP was 5.9% (95%CI: 3.9%-8.4%). Meta-regression revealed significant association of pancreatic enzyme replacement therapy (PERT) use with prevalence of osteoporosis [coefficient: 1.7 (95%CI: 0.6-2.8); P < 0.0001]. We observed no associations with mean age, sex distribution, body mass index, alcohol or smoking exposure, diabetes with prevalence of osteopenia, osteoporosis or fragility fractures. Paucity of data on systemic inflammation, CP severity, and bone mineralization parameters precluded a formal meta-analysis. CONCLUSION: This meta-analysis confirms significant bone disease in patients with CP. Other than PERT use, we observed no patient or study-specific factor to be significantly associated with CP-related bone disease. Further studies are needed to identify confounders, at-risk population, and to understand the mechanisms of CP-related bone disease and the implications of treatment response.

Structural vaccinology-based design of multi-epitopes vaccine against Streptococcus gordonii and validation using molecular modeling and immune simulation approaches.

Streptococcus gordonii is an oral bacterium colonizing the dental cavity and leading to plaque formation. This pervasive colonizer is also the etiologic agent of bacterial endocarditis and has a major role in infective endocarditis. The bacteria reach the heart through oral bleeding, leading to inflammation of cardiovascular valves. Over the past 50 years, it has shown a significant pathogenic role in immunocompromised and neutropenic patients. Since antibiotic resistance has created prophylaxis failure towards infective endocarditis, a potent therapeutic candidate is needed. Therefore, multi-epitopes vaccine offers advantages over the other approaches. Thus, herein, numerous molecular-omics tools were exploited to mine immunogenic peptides, i.e., T-cell and B-cell epitopes, and construct a vaccine sequence. Our findings revealed a total of 24 epitopes, including CTL, HTL, and B-cell are responsible for imparting immune responses, which were combined with the help of different linkers, and MEVC was constructed. Multifactorial validation of the candidate vaccine was performed to minimize the risk factors. The final sequence was docked with TLR2 to validate its conformation compatibility with receptor and long-term interactions stability. Our analysis revealed that the vaccine construct is immunogenic and non-allergenic. The construct also established various contacts with the immune receptor. Finally, the vaccine sequence was reverse-translated, optimized for codon usage, and analyzed for expression in the Escherichia coli K12 strain. Maximum expression was noted with a CAI score of 0.95. In silico immune simulation revealed that the antigen was neutralized on the 3rd day after injection. In conclusion, the current study warrants validation of the vaccine construct both in in vitro and in vivo models for accurate therapeutic intervention.

A Rare Case of Undifferentiated Rhabdoid Carcinoma of the Colon.

Rhabdoid carcinoma of the colon is a rare type of malignancy that belongs to the family of malignant rhabdoid tumors (MRTs). This is infrequently encountered in clinical settings therefore data regarding treatment is lacking. Herein we discuss an elderly female patient who presented with severe abdominal pain in the setting of a gastrointestinal perforation. Imaging showed a large mass in the transverse colon, which was found to be an undifferentiated carcinoma of the colon with rhabdoid features. We highlight this case to discuss the clinical course of the patient, thereby adding to the limited literature that is available, as well as review the few studies that have, thus far, documented this rare presentation.

Hemorrhagic Pericardial Effusion From Apixaban Use: Case Report and Literature Review.

Direct oral anticoagulants (DOACs) have revolutionized therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation. These medications are generally well tolerated and are not associated with the inconvenience of repeat international normalized ratio (INR) checks. While bleeding in general is a common side effect associated with DOACs, especially from a gastrointestinal source, spontaneous hemorrhagic pericardial effusions are not seen frequently. Herein, we present a case of a patient who developed a hemorrhagic pericardial effusion three days after the initiation of apixaban. We also summarize the current data that is available showing this side effect and highlight an important risk factor that may predispose patients to this complication.

Infliximab-Induced Non-specific Interstitial Pneumonitis in a Patient With Ulcerative Colitis (UC).

Infliximab belongs to the family of tumor necrosis factor (TNF) alpha inhibitors and since its development, it has revolutionized treatment for both rheumatological diseases and inflammatory bowel disease (IBD). In IBD specifically, it has shown to result in symptomatic, endoscopic, and histological remission which is why it is one of the most widely used treatments for moderate to severe IBD. While common side effects include infections due to immunosuppression, cytopenias and hepatotoxicity, interstitial lung disease (ILD) has been infrequently reported to result from inflixiamb use. We present the case of a patient with ulcerative colitis (UC) who achieved remission with infliximab, however, after about two years of infusions, developed evidence of non-specific interstitial pneumonitis (NSIP). Extensive work up was done to rule out infections, mixed connective tissue disorders, and hypersensitivity pneumonitis. Although lung biopsy remains the gold standard for diagnosing NSIP; clinical, laboratory, and radiographic findings were sufficient in establishing this diagnosis. Initiation of empiric high dose steroids, and cessation of infliximab infusions showed improvement in respiratory status and resolution of lung findings. This case highlights the importance of recognizing adverse effects of infliximab on the pulmonary status of an IBD patient given that infliximab mediated ILD does not adhere to a specific timeline. Considering that respiratory function may be compromised post any number of infusions, it is imperative to acknowledge patients' respiratory complaints and initiate prompt investigation and evaluation for this rare complication.

Recurrent Chylous Pleural Effusions in a Patient Treated With Dasatinib.

Dasatinib is a second-generation BCR-ABL tyrosine kinase inhibitor (TKI) that is approved for the treatment of chronic myeloid leukemia (CML), a myeloproliferative disorder seen commonly in adults over the age of 50. Dasatinib is superior in tolerance and efficacy to first-generation TKIs such as imatinib, given its ability to target mutation products that are resistant to first-generation TKIs. One of the common side effects of dasatinib includes pleural effusion which can be seen in up to 25% of patients on treatment. These effusions are predominantly exudative; however, they tend to resolve upon discontinuation of the drug. While infrequent, chylous effusions have been reported with the use of dasatinib; they tend to resolve following discontinuation of the drug. We present a case of a patient who was treated with dasatinib and developed a chylous effusion which was refractory to the discontinuation of the medication. Our patient was switched to imatinib and since his first episode, he has had multiple reaccumulation requiring thoracentesis, all of which have revealed chylous pleural fluid as per fluid analysis. We present this case to highlight a rare adverse effect of dasatinib which, via an unknown mechanism, can potentially lead to irreversible damage to the lymphatic duct resulting in recurrent chylous effusions.

Pylephlebitis With Splenic and Mesenteric Vein Thrombosis in a Patient With Diverticulitis.

Diverticulitis is a common gastrointestinal complaint that refers to inflammation of colonic diverticula. Its incidence has increased partly due to the increase in prevalence of diverticulosis, which results from poor dietary habits and chronic constipation. An acute diverticulitis episode can vary in severity, ranging from outpatient management of mild abdominal discomfort to inpatient admission requiring emergent surgery. Some common complications associated with diverticulitis include bowel wall perforation, microperforation, abscess formation, bowel obstruction, and colonic fistulas. A lesser-known complication of diverticulitis is pylephlebitis. Pylephlebitis refers to thrombosis of the portal vein resulting from sepsis secondary to an intra-abdominal or pelvic infection. Initially thought to be most associated with appendicitis, literature has emerged that implicates diverticulitis as the most likely culprit. Less frequently, pylephlebitis can also include thrombosis of the abdominal vasculature that drains into the portal vein such as the mesenteric veins and splenic vein. Despite antibiotic therapy, mortality in patients with pylephlebitis is high as it can lead to bowel ischemia, liver failure, or liver abscesses. While antibiotic therapy is the mainstay of treatment, anticoagulation can also be used in conjunction, especially when thrombosis extends beyond the portal vein. Herein, we present a case of a patient who was diagnosed with pylephlebitis with thrombosis extension into the splenic and mesenteric veins, which resulted from an episode of severe sigmoid diverticulitis. Our patient was treated medically with antibiotics and anticoagulation and underwent a loop transverse colostomy with full recovery. He was discharged with intravenous antibiotics and long-term anticoagulation. We present this case to highlight a rare complication of an otherwise common pathology and describe our management that led to a positive outcome for this patient.

Recurrence of Angioimmunoblastic T-cell Lymphoma in a Patient Successfully Treated for Hodgkin's Lymphoma: A Case Report.

Hodgkin's lymphoma (HL) is a common and potentially curable malignancy that has an overall good prognosis when timely treatment with chemoradiation is delivered. Recurrence of malignancy is one complication seen in patients successfully treated for HL. In most cases, the recurring malignancy can be a solid tumor or leukemia. While recurrence of a non-HL (NHL) has been reported, this is relatively uncommon. Angioimmunoblastic T-cell lymphoma (AITL) is a rare nodal appearing, peripheral T-cell lymphoma and represents 2% of all NHLs. Its clinical features include generalized lymphadenopathy, varying constitutional symptoms, and autoimmune-related hematologic findings, such as hemolytic anemia and or thrombocytopenia. Diagnosis is made based on histological and immunohistochemical (IHC) findings, which show evidence of T-cells, follicular T-cell markers, and characteristic genomic features including mutations of T-cell receptor or T-cell receptor signaling genes. It is a characteristically aggressive cancer with a poor prognosis if untreated and therefore requires prompt diagnosis. While sporadic AITL is rare on its own, data on AITL occurrence in patients previously treated for HL is lacking. We present a peculiar case of an 80-year-old patient who was diagnosed and treated for stage IV Hodgkin's disease only to be later diagnosed with AITL.

An Atypical Presentation of Twiddler's Syndrome: A Case Report.

The prevalence of implanted pacemaker/defibrillator devices continues to rise. Automatic implantable cardioverter-defibrillator (AICD) lead displacement (Twiddler's syndrome) is an uncommon form of the device malfunction, usually presenting with cardiac symptoms. We present a case of Twiddler's syndrome with an atypical presentation, accompanied by critical alkalosis on arterial blood gas. Considering Twiddler's syndrome as part of the differential diagnosis in patients with implanted devices and utilizing remote ICD interrogation may improve the care of patients presenting with device malfunction.

Transformed Waldenström Macroglobulinemia Responsive to Tafasitamab Plus Lenalidomide: A Case Report.

The histologic transformation (HT) of Waldenström macroglobulinemia (WM) into diffuse large-cell lymphoma is an uncommon but poor-prognostic event for which there is no standard therapy. Knowledge of this entity is mainly derived from largely retrospective studies, which report abysmal average survival rates even with the utilization of first-line chemoimmunotherapy and especially in patients who meet the high-risk criteria based on prognostic indices used for WM. We present the case of a 75-year-old man with high-risk, transformed WM who was ineligible for standard chemoimmunotherapy (due to pancytopenia and multiple comorbidities) and was consequently treated with tafasitabmab, an anti-CD19 monoclonal antibody plus lenalidomide. Tafasitamab plus lenalidomide (TAF/LEN) is a recently approved therapy for relapsed or refractory de novo diffuse large-cell lymphoma (DLCL) but has not been previously studied in transformed low-grade lymphomas or WM. We show that TAF/LEN resulted in a complete and durable response of the DLCL by PET/CT and a complete bone marrow response of lymphoplasmacytoid cells, including the normalization of complex cytogenetic abnormalities. The extraordinary response of our patient to TAF/LEN suggests that this combination may be an effective and tolerable therapy for transformed WM as well as relapsed or refractory non-transformed WM. Clinical trials of TAF/LN for the treatment of Waldenström macroglobulinemia are recommended.

Correction: Transformed Waldenström Macroglobulinemia Responsive to Tafasitamab Plus Lenalidomide: A Case Report.

[This corrects the article DOI: 10.7759/cureus.32403.].

Transit time flow measurement and outcome in coronary artery bypass grafting for surgeon and trainee.

BACKGROUND: Trainees need to operate under appropriate supervision to become competent. Transit time flow measurement (TTFM) is useful in detecting intraoperative graft failures during coronary artery bypass grafting (CABG). This study aims to compare the intra- and postoperative outcomes, including TTFM, of isolated CABG performed by a single consultant versus trainees and to determine the relationship between the pulsatility index (PI) and postoperative outcomes. METHODS: This retrospective study included 155 isolated CABG cases. Intraoperative outcomes included duration of cardiopulmonary bypass (CPB) and aortic cross-clamp and TTFM for arterial and venous grafts. Postoperative outcomes included common postoperative complications and mortality. The odds ratios of postoperative complications and mortality for arterial and venous grafts with PI ≤3 relative to grafts with PI >3 were determined with multiple logistic regression. RESULTS: The duration of CPB and aortic cross-clamp was significantly shorter in the consultant's group. TTFM for both arterial and venous grafts were similar and no significant differences in postoperative complications and mortality were detected between the two groups. Patients with arterial grafts with PI ≤3 were less likely to require an intra-aortic balloon pump (IABP) or be ventilated for a prolonged period. No significant differences in postoperative outcomes and mortality were detected between venous grafts with PI ≤3 and PI >3. CONCLUSIONS: Trainees can achieve good results in isolated CABG with appropriate case selection. Patients with arterial grafts with PI ≤3 have better postoperative outcomes.

CytomegaloVirusDb: Multi-omics knowledge database for cytomegaloviruses.

Cytomegalovirus infection is a significant health concern and need further exploration in immunologic response mechanisms during primary and reactivated CMV infection. In this work, we evaluated the whole genomes and proteomes of different CMV species and developed an integrated open-access platform, CytomegaloVirusDb, a multi-Omics knowledge database for Cytomegaloviruses. The resource is categorized into the main sections "Genomics," "Proteomics," "Immune response," and "Therapeutics,". The database is annotated with the list of all CMV species included in the study, and available information is freely accessible at http://www.cmvdb.dqweilab-sjtu.com/index.php. Various parameters used in the analysis for each section were primarily based on the whole genome or proteome of each specie. The platform provided datasets are open to access for researchers to obtain CMV species-specific information. This will help further to explore the dynamics of CMV-specific immune response and therapeutics. This platform is a useful resource to aid in advancing research against Cytomegaloviruses.

BC-TFdb: a database of transcription factor drivers in breast cancer.

Transcription factors (TFs) are DNA-binding proteins, which regulate many essential biological functions. In several cancer types, TF function is altered by various direct mechanisms, including gene amplification or deletion, point mutations, chromosomal translocations, expression alterations, as well as indirectly by non-coding DNA mutations influencing the binding of the TF. TFs are also actively involved in breast cancer (BC) initiation and progression. Herein, we have developed an open-access database, BC-TFdb (Breast Cancer Transcription Factors database), of curated, non-redundant TF involved in BC. The database provides BC driver TFs related information including genomic sequences, proteomic sequences, structural data, pathway information, mutations information, DNA binding residues, survival and therapeutic resources. The database will be a useful platform for researchers to obtain BC-related TF-specific information. High-quality datasets are downloadable for users to evaluate and develop computational methods for drug designing against BC. Database URL: https://www.dqweilab-sjtu.com/index.php.