Revolutionizing chronic endometritis diagnosis: real-time polymerase chain reaction unveils microbial pathogens in Indian women with abnormal bleeding and reproductive challenges.

Background: This study aimed to assess the utility of real-time-polymerase chain reaction (PCR) for diagnosing chronic endometritis (CE) by targeting 11 prevalent pathogens and to compare the outcomes with conventional culture-based diagnosis. Study Design: A retrospective analysis was conducted on 500 patients with clinical conditions such as abnormal bleeding, in vitro fertilization failure, recurrent implantation failure, recurrent miscarriage, and recurrent pregnancy loss. The prevalence of 11 key pathogens associated with CE was evaluated in endometrial biopsy samples. Results: In our study, PCR identified 318 cases (63.6%) positive for at least one of the 11 investigated pathogens, while culture-based methods detected 115 cases (23%). Predominant pathogens detected by PCR included Enterococcus faecalis (E. faecalis) (19%), Escherichia coli (E. coli) (6.8%), Staphylococcus aureus (S. aureus) (9%), Mycoplasma hominis (5%), Mycoplasma genitalium (6.2%), Streptococcus agalactiae (S. agalactiae) (4.2%), Ureaplasma urealyticum (4%), nontuberculous Mycobacterium (5.2%), Mycobacterium tuberculosis (1.2%), Neisseria gonorrhoeae (0.6%), and Chlamydia trachomatis (2.4%). Standard culture methods identified E. faecalis (10.8%), S. aureus (6.2%), E. coli (3.8%), and S. agalactiae (2.2%). Conclusion: The DICE panel proves itself as a swift, precise, and cost-effective diagnostic tool for detecting both culturable and nonculturable endometrial pathogens in CE. Demonstrating superiority, the Molecular method outshines microbial culture, ensuring accurate and sensitive detection of CE-associated pathogens, harmonizing seamlessly with histology and hysteroscopy findings.

Review article: Telecare in gastroenterology-Within the COVID-19 pandemic and beyond.

BACKGROUND: Telehealth is a growing model of care, greatly accelerated with the demands of the COVID-19 pandemic. Telecare is a synchronous audio-visual or audio-only format of health delivery. AIMS: To evaluate the existing literature on telecare within adult gastroenterology subspecialties to determine if outcomes are comparable to traditional in-person consultations and to highlight the Pokapu Network, a local initiative in the Lakes Region of New Zealand, amongst these international findings. METHODS: We completed an OVID MEDLINE search using the terms gastroenterology, endoscopy, digestive system, inflammatory bowel disease, functional, hepatology, liver, telemedicine, telehealth, videoconferencing, remote consultation, video clinic and telephone clinic. RESULTS: Patients showed positive attitudes towards telecare and, in several reports, would elect to have telecare consults in the future. Telecare reduces travel time and out-of-pocket costs for patients and the need for patients to take time off work. Generally, patients engaging with telecare show equivalent health outcomes to patients engaging with traditional models of care. Patients from ethnic minority groups or lower socio-economic backgrounds, or who are older, are less likely to complete a 'successful' telecare consult. CONCLUSION: Telecare is a useful model of care to allow gastroenterology centres to function within the context of COVID-19 isolation and beyond. It has significant benefits for patients who face geographical and financial barriers to accessing healthcare. Telecare models such as the Pokapu Network hold promise in reducing inequities for gastroenterology patients. Such models must be introduced with consideration of digital disparities that exist amongst patients to avoid worsening the digital divide.

Biodegradation of phenanthrene by piezotolerant Bacillus subtilis EB1 and genomic insights for bioremediation.

A marine strain B. subtilis EB1, isolated from Equator water, showed excellent degradation towards a wide range of hydrocarbons. Degradation studies revealed dense growth with 93 % and 83 % removal of phenanthrene within 72 h at 0.1 and 20 MPa, respectively. The identification of phenanthrene degradation metabolites by GC-MS combined with its whole genome analysis provided the pathway involved in the degradation process. Whole genome sequencing indicated a genome size of 3,983,989 bp with 4331 annotated genes. The genome provided the genetic compartments, which includes monooxygenase, dioxygenase, dehydrogenase, biosurfactant synthesis catabolic genes for the biodegradation of aromatic compounds. Detailed COG and KEGG pathway analysis confirmed the genes involved in the oxygenation reaction of hydrocarbons, piezotolerance, siderophores, chemotaxis and transporter systems which were specific to adaptation for survival in extreme marine habitat. The results of this study will be a key to design an optimal bioremediation strategy for oil contaminated extreme marine environment.

Health system resilience: Ensuring TB services during COVID-19 pandemic in Kerala, India.

COVID-19 pandemic has affected TB case detection and continuity of care globally. Kerala, the southern Indian state has experienced a reduction in TB notification during second and third quarter of 2020. Through (1) causal analysis (2) meticulous planning and establishment of systems (3) locally customised guidelines (4) better management of resources (5) integration with other programs and (6) good partnership with private sector, Kerala was able to catch up the TB notification and ensure that TB services remain intact even during the COVID-19 pandemic. Approach to catch up TB diagnosis included (1) Field based active case finding among the vulnerable individuals, (2) bilateral screening for TB and COVID-19, (3) enhancement of biosafety in laboratories, (4) strengthening of specimen collection and transportation systems, (5) targeted advocacy and communication to find out missed cases and (6) effective partnership with the private sector. Current experiences also show that TB case finding could be improved and delay in diagnosis could be averted by integrating TB case finding into the screening and testing systems established for COVID-19. The experiences of ensuring TB services during pandemic in Kerala also affirms the importance of maintaining an integrated and strong TB control component in the public health sector and vesting ownership of the TB control programme with the primary health care team. Community-based and community-led responses that take diagnosis, care, and support to the doors of those affected have much potential in delivering TB services in the subsequent years of pandemic.

Dual PI3Kδγ inhibition demonstrates potent anticancer effects in diffuse large B-cell lymphoma models: Discovery and preclinical characterization of LL-00084282.

Phosphoinositide 3-kinase (PI3K) pathway mediates key signaling events downstream to B-cell receptor (BCR) for survival of mature B-cells, and overexpression or overactivation of PI3Kδ is crucial for B-cell malignancies such as diffuse large B-cell lymphoma (DLBCL). Small molecule PI3Kδγ inhibitors, with a known potential to reduce activated B-cell (ABC)-DLBCL transformation, form an important class of therapeutics approved for follicular lymphoma (FL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL). In this study, we describe discovery of a potent, selective and efficacious dual PI3Kδγ inhibitor, LL-00084282, having a differentiated efficacy profile in human ABC- and germinal center B-cell (GCB)-DLBCL cell lines. LL-00084282 displayed high potency and superior PI3Kδγ engagement with excellent selectivity over other PI3K isoforms at both IC50/90 concentrations in biochemical and cell-based assays. In contrast to selective PI3Kδ inhibitors, LL-00084282 showed superior and potent anticancer activity in both ABC- and GCB-DLBCL cell lines. LL-00084282 demonstrated in-vivo efficacy in OCI-Ly10 and SU-DHL-6 xenografts with good tolerability. Furthermore, LL-00084282 inhibited pro-inflammatory cytokine secretion and reduced basophil activation in human PBMCs, showing potential implications in immunoinflammatory conditions. Good pharmacokinetic properties in higher species and desirable efficacy profile highlights potential of this novel PI3Kδγ inhibitor for further clinical evaluation in DLBCL patients.

Cytomegalovirus infection among patients with cancer receiving immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs), used for the treatment of solid and hematologic malignancies, come with the risk of immune-related adverse events (irAEs). Opportunistic infections (e.g., cytomegalovirus [CMV]) mimic irAE symptoms and are understudied in this population. We aimed to describe the incidence, characteristics, treatment and outcomes of CMV infection in ICI-treated patients. Methods: We conducted a single-center retrospective review of all adult patients who were CMV-positive after ICI therapy between 06/2011 and 05/2020. A CMV-positive non-ICI cohort was matched to the ICI group based on age, sex and cancer type. Variables of interest were collected through electronic medical records. Results: The study population comprised 192 patients overall. CMV infection incidence was 7.7% in ICI patients and 12.9% in non-ICI patients (P<0.001). Rates of infection clearance (83% vs. 50%, P=0.002) and recurrence (20% vs. 3%, P=0.037) were higher in ICI patients with hematologic vs. solid tumors, despite similar treatments. All-cause mortality was higher in solid rather than hematologic malignancies in ICI patients (83% vs. 54%, P=0.009); CMV-related mortality was low (3-4%) in both groups. Conclusions: CMV infection occurred in about 7.7% of the ICI-treated cancer population. The infection can be disseminated in multiple organs and has a wide spectrum of clinical symptoms. ICI-treated patients with a hematologic malignancy had higher viral clearance and recurrence than those with solid tumors. In this study, CMV itself did not lead to high mortality in cancer patients. Further study is needed to investigate the role of CMV infection in patients' irAEs and cancer outcome.

Low but increasing rates of inflammatory bowel disease in Maori: a report from Lakes District Health Board IBD.

Inflammatory bowel diseases (IBD) are chronic, inflammatory diseases that are increasingly prevalent in New Zealand. Previous regional studies describe significantly lower rates of IBD in Maori compared to non-Maori. This article reports the prevalence and incidence of IBD at Lakes District Health Board, and discusses potential contributing factors to the observed increasing incidence rates in Maori. Although the rates are still less than non-Maori, colonisation with increased urbanisation and changes in diet and hygiene suggest that IBD rates may continue to increase in Maori.

Reducing mortality in mucormycosis of the head and neck in diabetic patients: A CARE case series.

INTRODUCTION: Rhinocerebral mucormycosis is extremely fatal, with mortality rates ranging from 85-93% despite the best treatment in immunocompromised patients. We emphasize the importance of early diagnosis, repeated debridement, and aggressive antifungal treatment to reduce mortality. CASE SUMMARY: We report six cases (five male and one female), with a mean age of 51 years who were diagnosed to have mucormycosis from 2017 to 2019. All patients were diabetic. Intracranial involvement and orbital involvement were found in four cases. Facial nerve palsy was seen in two cases, one without any apparent otological involvement. Aggressive serial debridement and amphotericin B was started. Posaconazole was added subsequently to the treatment in two cases. One patient succumbed to the disease five months after discharge. The other five patients are on regular follow-up for a mean duration of 14 months at the end of which two had residual disease which was under control. DISCUSSION: Repeated surgical debridement with an early aggressive and combination antifungal therapy can result in good outcomes even in advanced mucormycosis. Concurrent management of the underlying pathology, monitoring of liver and kidney functions, and therapeutic drug monitoring are useful to ensure smooth and effective treatment.

A 5-year retrospective review of skin adnexal tumours received at a tertiary dermatopathology service: implications for linked genetic diagnoses.

BACKGROUND: Skin adnexal tumours (SATs) comprise a diverse range of neoplasms, which are difficult to diagnose clinically. They present in paediatric and adult populations, and may be indicative of an underlying genetic syndrome. There is a lack of recent data on the presentation of these tumours in clinical practice in European populations. OBJECTIVES: To characterize the clinical and pathological features of SATs received at a single tertiary centre over a 5-year period. METHODS: A retrospective health record audit of SATs received at the Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, during the period November 2012 to October 2017 was performed. RESULTS: In total, 107 144 skin cases were received during the audit period. A total of 1615 cases of SATs from 1359 patients were included; 1570 (97·2%) were benign and 45 (2·8%) were malignant. Overall, the average age at presentation was 55 years (range 11 months to 97 years) and the male to female ratio was 0·77 : 1. Sweat gland and hair follicle SATs were most frequently excised; in adults, the most frequent tumour was hidrocystoma, and in children, pilomatrixoma occurred most often. Prebiopsy diagnosis was correct in 28% of cases. Benign SATs are often markers of an associated genetic condition, which warrants improved discrimination of sporadic from genetically related SATs. CONCLUSIONS: SATs are difficult to diagnose clinically, and clinicopathological correlation may help enhance discrimination of genetically related SATs from sporadic cases. These data have implications for clinical and dermatopathological training provision, the development of reporting standards, and genetic assessment of selected patients.

Self-Inflicted Pneumomediastinum: A Case Report.

Self-inflicted wound can present with various scenarios. It is well known that the purpose of a self-inflicted wound is to avoid obligatory duties. During war, soldiers get self-inflicted wounds to seek medical leave in the hope to save their lives from deadly battle. Self-induced pneumomediastinum from oral lesion with valsalva maneuver was a rare practice among prisoners to get rid of that imprisoned life and to stay in the hospital. Self-inflicted wound is also commonly seen in patient with psychosomatic disorders. It relates observations from forensic medicine and psychiatry to specific clinical symptoms, toxicological circumstances and social influences e.g. stress incurred by everyday life, war, imprisonment etc. In particular cases, it clears up criminal and civil jurisdiction. It also gives importance to private insurers about cases of self-mutilation. There is also concern about insurers, forensic scientists and psychiatrist about their responsibilities and the procedure they follow in the examination, their jurisdiction and the treatment involving the cases of self-inflected injuries. To our knowledge, self-inflicted subcutaneous emphysema causing pneumomediastinum by a normal young boy out of curiosity and without any apparent ill motive, is an unusual finding and possibly no such case report was published before.

Clinicopathologic Features, Treatment Response, and Outcomes of Immune Checkpoint Inhibitor-Related Esophagitis.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) have provided practice-changing outcomes in treating many cancers, ICI-related gastrointestinal toxicity can limit their use. Upper gastrointestinal toxicity is not common nor as well described as lower gastrointestinal toxicity. We aimed to characterize the clinical presentation, endoscopic and histologic features, treatment response, and outcomes of ICI-related esophagitis. METHODS: We retrospectively studied patients at The University of Texas MD Anderson Cancer Center in whom esophagitis developed after receiving ICIs from June 2011 through January 2020. We included patients with endoscopic evidence of esophagitis and excluded those with other obvious causes of esophagitis. A chi-square test was used to assess associations between categorical variables. The Mann-Whitney U test was used to compare differences between continuous variables. RESULTS: Of 657 consecutive patients who underwent esophagogastroduodenoscopy (EGD) during or within 6 months of completing ICI-based therapy, 21 (3%) had esophagitis deemed to be from ICIs. Of these patients, 1 (5%) received an inhibitor of CTLA-4 alone, 15 (71%) received anti-PD-1 or PD-L1 monotherapy, and 5 (24%) received a combination of these. Median time from ICI initiation to onset of esophagitis was 4 months. Upon evaluation with EGD, only 3 patients (14%) had isolated esophageal involvement; 18 (86%) had concurrent involvement of the stomach, duodenum, or both. Most patients (67%) were treated with proton pump inhibitors, and 4 (19%) received steroids (prednisone or budesonide). The mortality rate was 38% (median follow-up, 15 months). CONCLUSIONS: Esophagitis associated with ICI use is rare. The diagnosis is one of exclusion because its clinical presentation appears similar to that of inflammation resulting from other causes. It often occurs in conjunction with other upper gastrointestinal toxicity. Symptoms are mild and respond well to nonimmunosuppressive treatment, with few severe complications.