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Background: The shoulder microbiome is an emerging field in orthopedic research. Large synovial joints which were typically considered to be sterile now have strong evidence demonstrating the presence of native organisms colonizing the joint. Many of the conditions that surgeons see and treat in the shoulder, including osteoarthritis, rotator cuff tears, and adhesive capsulitis, have unclear etiology. The shoulder microbiome is a potential source of pathology in dysbiosis states, or source of protection against pathology in normobiosis states. The purpose of this review is to characterize the published research detailing the microbiome of the native shoulder joint. Methods: We conducted a systematic review and meta-analysis of data searches on Medline, Embase, Cochrane Central Register of Controlled Trials, and SCOPUS. The following search terms were used with various permutations; shoulder, skin, microbiome, infection, colonization, commensal, microbiota, flora. The terms ‘shoulder’ and ‘shoulder AND skin’ were combined with the other 6 terms for a total of 12 searches per database. Two independent reviewers conducted the review with a third reviewer available to resolve differences of interpretation. Studies were eligible if they were human studies of patients undergoing shoulder surgery (or surgical preparation therapy) with a shoulder that had not previously been operated on, where microbial samples were reported. Studies were excluded if they were systematic reviews and meta-analyses, animal studies, cadaveric studies, studies of patients under the age of 18 and studies including postoperative shoulders. Results: The search methodology yielded 47 eligible studies for analysis, with a total of 3283 patients. Native shoulder sampling yielded positive organisms in 50.8% of all samples (95% confidence interval [CI] = 41.8%-59.8%, I2 = 97.9%, P = .000). The predominate organism reported was C. acnes, with 29% of studies specific for C. acnes, and a total of 52 other organisms detected in the native shoulder. Skin preparation solutions reduced the skin colonization rate of 55.7% (95% CI = 32.7%-78.6%, I2 = 98.2%, P = .000) to 43.5% (95% CI = 29.5%-57.5%, I2 = 98.2%, P = .000). Despite the high rates of colonization detected under sterile conditions, of 42 studies and 3083 patients reporting postoperative outcomes, the infection rate was 1.8% (95% CI = 0.5%-3.2%, I2 = 0.0%, P = .612). Conclusion: There is strong evidence to support the existence of a native shoulder microbiome. Further research is required to characterize this microbiome and correlate it to disease and health states.

Aims: Periprosthetic fractures (PPFs) following hip arthroplasty are complex injuries. This study evaluates patient demographic characteristics, management, outcomes, and risk factors associated with PPF subtypes over a decade. Methods: Using a multicentre collaborative study design, independent of registry data, we identified adults from 29 centres with PPFs around the hip between January 2010 and December 2019. Radiographs were assessed for the Unified Classification System (UCS) grade. Patient and injury characteristics, management, and outcomes were compared between UCS grades. A multinomial logistic regression was performed to estimate relative risk ratios (RRR) of variables on UCS grade. Results: A total of 1,104 patients were included. The majority were female (57.9%; n = 639), ethnically white (88.5%; n = 977), used mobility aids (67%; n = 743), and had a median age of 82 years (interquartile range (IQR) 74 to 87). A total of 77 (7%) had pain prior to the PPF. The most common UCS grade was B2 (33%; n = 368). UCS type D fractures had the longest length of stay (median 19 days (IQR 11 to 26)), highest readmission to hospital (21%; n = 9), and highest rate of discharge to step-down care (52%; n = 23). Multinomial regression suggests that uncemented femoral stems are associated with a reduced risk of UCS C (RRR 0.36 (95% confidence interval (CI) 0.2 to 0.7); p = 0.002) and increased risk of UCS A (RRR 3.3 (95% CI 1.9 to 5.7); p < 0.001), compared to UCS B fracture. Conclusion: The most common PPF type in elderly frail patients is UCS B2. Uncemented stems have a lower risk of UCS C fractures compared to cemented stems. A national PPF database is needed to further identify correlation between implants and fracture subtypes. Cite this article: Bone Jt Open 2023;4(9):659–667.

Systems for disease vector control should be effective, efficient, and flexible to be able to tackle contemporary challenges and threats in the control and elimination of vector-borne diseases. As a priority activity towards the strengthening of vector control systems, it has been advocated that countries conduct a vector-control needs assessment. A review was carried out of the perceived needs for disease vector control programs among eleven countries and subnational states in South Asia and the Middle East. In each country or state, independent teams conducted vector control needs assessment with engagement of stakeholders. Important weaknesses were described for malaria, dengue and leishmaniases regarding vector surveillance, insecticide susceptibility testing, monitoring and evaluation of operations, entomological capacity and laboratory infrastructure. In addition, community mobilization and intersectoral collaboration showed important gaps. Countries and states expressed concern about insecticide resistance that could reduce the continued effectiveness of interventions, which demands improved monitoring. Moreover, attainment of disease elimination necessitates enhanced vector surveillance. Vector control needs assessment provided a useful planning tool for systematic strengthening of vector control systems. A limitation in conducting the vector control needs assessment was that it is time- and resource-intensive. To increase the feasibility and utility of national assessments, an abridged version of the guidance should focus on operationally relevant topics of the assessment. Similar reviews are needed in other regions with different contextual conditions.

Introduction: Brucellosis is a neglected zoonotic disease of major public health concern. In India, the incidence of brucellosis remains vastly underreported due to its non-specific clinical presentation and sub-optimal sensitivity of existing gold standard tests. Studies in Northeast India have shown high incidences of brucellosis in livestock, but the region lacks data on human brucellosis despite its high associated risk. In the present study, we report the seroprevalence of human brucellosis and its associated risk factors in Meghalaya, Northeast India. Materials and Methods: A prospective observational study was conducted in East Khasi Hills and Ri.Bhoi districts of Meghalaya, from July 2018 to July 2020. A total of 1046 suspected patients with febrile illness along with associated risk factors were recruited through camps and various diagnostic laboratories in the defined region as per the pre.specified inclusion and exclusion criteria. Baseline, demographics, and clinical characteristics were recorded of all the consenting participants. Blood samples were analyzed for brucellosis-specific IgM antibodies through enzyme-linked immunosorbent assay (ELISA). Results and discussion: The overall seroprevalence of brucellosis was found to be 11.37% in Meghalaya. Among recruited participants, females were found to be more susceptible than males. Risk factors such as consumption of meat were found to be more significantly associated with brucellosis disease in the study region. Among the clinical presentations, pyrexia of unknown origin, myalgia, and chronic fatigue syndrome were found to be significantly associated with brucellosis disease in IgM.positive cases. Conclusion: Our result suggests further epidemiological investigations for human brucellosis in Northeast India toward improved advocacy for accurate diagnosis, and development of proper response mechanism in areas of high endemicity.

Abstract Insecticides have played a major role in the prevention, control, and elimination of vector-borne diseases, but insecticide resistance threatens the efficacy of available vector control tools. A global survey was conducted to investigate vector control insecticide use from 2010 to 2019. Out of 140 countries selected as sample for the study, 87 countries responded. Also, data on ex-factory deliveries of insecticide-treated nets (ITNs) were analyzed. Insecticide operational use was highest for control of malaria, followed by dengue, leishmaniasis and Chagas disease. Vector control relied on few insecticide classes with pyrethroids the most used overall. Results indicated that IRS programs have been slow to react to detection of pyrethroid resistance, while proactive resistance management using insecticides with unrelated modes of action was generally weak. The intensive use of recently introduced insecticide products raised concern about product stewardship regarding the preservation of insecticide susceptibility in vector populations. Resistance management was weakest for control of dengue, leishmaniasis or Chagas disease. Therefore, it will be vital that vector control programs coordinate on insecticide procurement, planning, implementation, resistance monitoring, and capacity building. Moreover, increased consideration should be given to alternative vector control tools that prevent the development of insecticide resistance.

Abstract Background Long-lasting insecticide nets (LLINs) are a core malaria intervention. LLINs should retain efficacy against mosquito vectors for a minimum of three years. Efficacy and durability of Olyset® Plus, a permethrin and piperonyl butoxide (PBO) treated LLIN, was evaluated versus permethrin treated Olyset® Net. In the absence of WHO guidelines of how to evaluate PBO nets, and considering the manufacturer’s product claim, Olyset® Plus was evaluated as a pyrethroid LLIN. Methods This was a household randomized controlled trial in a malaria endemic rice cultivation zone of Kirinyaga County, Kenya between 2014 and 2017. Cone bioassays and tunnel tests were done against Anopheles gambiae Kisumu. The chemical content, fabric integrity and LLIN survivorship were monitored. Comparisons between nets were tested for significance using the Chi-square test. Exact binomial distribution with 95% confidence intervals (95% CI) was used for percentages. The WHO efficacy criteria used were ≥ 95% knockdown and/or ≥ 80% mortality rate in cone bioassays and ≥ 80% mortality and/or ≥ 90% blood-feeding inhibition in tunnel tests. Results At 36 months, Olyset® Plus lost 52% permethrin and 87% PBO content; Olyset® Net lost 24% permethrin. Over 80% of Olyset® Plus and Olyset® Net passed the WHO efficacy criteria for LLINs up to 18 and 12 months, respectively. At month 36, 91.2% Olyset® Plus and 86.4% Olyset® Net survived, while 72% and 63% developed at least one hole. The proportionate Hole Index (pHI) values representing nets in good, serviceable and torn condition were 49.6%, 27.1% and 23.2%, respectively for Olyset® Plus, and 44.9%, 32.8% and 22.2%, respectively for Olyset® Net but were not significantly different. Conclusions Olyset® Plus retained efficacy above or close to the WHO efficacy criteria for about 2 years than Olyset® Net (1–1.5 years). Both nets did not meet the 3-year WHO efficacy criteria, and showed little attrition, comparable physical durability and survivorship, with 50% of Olyset® Plus having good and serviceable condition after 3 years. Better community education on appropriate use and upkeep of LLINs is essential to ensure effectiveness of LLIN based malaria interventions. Graphical Abstract

Abstract Background Vector control plays a critical role in the prevention, control and elimination of vector-borne diseases, and interventions of vector control continue to depend largely on the action of chemical insecticides. A global survey was conducted on the management practices of vector control insecticides at country level to identify gaps to inform future strategies on pesticide management, seeking to improve efficacy of interventions and reduce the side-effects of chemicals used on health and the environment. Methods A survey by questionnaire on the management practices of vector control insecticides was disseminated among all WHO Member States. Data were analysed using descriptive statistics in MS Excel. Results Responses were received from 94 countries, or a 48% response rate. Capacity for insecticide resistance monitoring was established in 68–80% of the countries in most regions, often with external support; however, this capacity was largely lacking from the European & Others Region (i.e. Western & Eastern Europe, North America, Australia and New Zealand). Procurement of vector control insecticides was in 50–75% of countries taking place by agencies other than the central-level procuring agency, over which the central authorities lacked control, for example, to select the product or assure its quality, highlighting the importance of post-market monitoring. Moreover, some countries experienced problems with estimating the correct amounts for procurement, especially for emergency purposes. Large fractions (29–78%) of countries across regions showed shortcomings in worker safety, pesticide storage practices and pesticide waste disposal. Shortcomings were most pronounced in countries of the European & Others Region, which has long been relatively free from mosquito-borne diseases but has recently faced challenges of re-emerging vector-borne diseases. Conclusions Critical shortcomings in the management of vector control insecticides are common in countries across regions, with risks of adverse pesticide effects on health and the environment. Advocacy and resource mobilization are needed at regional and country levels to address these challenges.

Aims: It is imperative to understand the risks of operating on urgent cases during the COVID-19 (SARS-Cov-2 virus) pandemic for clinical decision-making and medical resource planning. The primary aim was to determine the mortality risk and associated variables when operating on urgent cases during the COVID-19 pandemic. The secondary objective was to assess differences in the outcome of patients treated between sites treating COVID-19 and a separate surgical site. Methods: The primary outcome measure was 30-day mortality. Secondary measures included complications of surgery, COVID-19 infection, and length of stay. Multiple variables were assessed for their contribution to the 30-day mortality. In total, 433 patients were included with a mean age of 65 years; 45% were male, and 90% were Caucasian. Results: Overall mortality was 7.6% for all patients and 15.9% for femoral neck fractures. The mortality rate increased from 7.5% to 44.2% in patients with fracture neck of femur and a COVID-19 infection. The COVID-19 rate in the 30-day postoperative period was 11%. COVID-19 infection, age, and Charlson Comorbidity Index were independent risk factor for mortality. Conclusion: There was a significant risk of contracting COVID-19 due to being admitted to hospital. Using a site which was not treating COVID-19 respiratory patients for surgery did not identify a difference with respect to mortality, nosocomial COVID-19 infection, or length of stay. The COVID-19 pandemic significantly increases perioperative mortality risk in patients with fractured neck of femora but patients with other injuries were not at increased risk.

BackgroundVisceral leishmaniasis (VL) is targeted for elimination as a public health problem in Nepal by 2023. For nearly three decades, the core vector control intervention in Nepal has been indoor residual spraying (IRS) with pyrethroids. Considering the long-term use of pyrethroids and the possible development of resistance in the vector Phlebotomus argentipes sand flies, we monitored the susceptibility status of their field populations to the insecticides of different classes, in villages with and without IRS activities in recent years.Methodology/principal findingsSand flies were collected from villages with and without IRS in five VL endemic districts from August 2019 to November 2020. The WHO susceptibility test procedure was adopted using filter papers impregnated at the discriminating concentrations of insecticides of the following classes: pyrethroids (alpha-cypermethrin 0.05%, deltamethrin 0.05%, and lambda-cyhalothrin 0.05%), carbamates (bendiocarb 0.1%) and organophosphates (malathion 5%). Pyrethroid resistance intensity bioassays with papers impregnated with 5× of the discriminating concentrations, piperonyl butoxide (PBO) synergist-pyrethroid bioassays, and DDT cross-resistance bioassays were also performed. In the IRS villages, the vector sand flies were resistant (mortality rate Conclusions/significanceOur investigation showed that P. argentipes sand flies have emerged with pyrethroid resistance, suggesting the need to switch to alternative classes of insecticides such as organophosphates for IRS. We strongly recommend the regular and systematic monitoring of insecticide resistance in sand flies to optimize the efficiency of vector control interventions to sustain VL elimination efforts in Nepal.

Introduction: Viral infections of Central Nervous System (CNS) are associated with severe neurological sequelae and can lead to significant morbidity, if not adequately diagnosed and treated. An immunological assay detecting antibodies in the Cerebrospinal Fluid (CSF) of the patients is widely used for diagnosis of viral infections of the CNS. In the present study, diagnostic efficacy of in-house designed synthetic peptide based Enzyme Linked Immunosorbent Assay (ELISA) was evaluated for detection of antibodies against neurotropic viruses panel such as Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Varicella Zoster Virus (VZV), Japanese Encephalitis Virus (JEV), Dengue (DENV), West Nile Virus (WNV) and Chandipura Virus (CHPV) in CSF of suspected cases. Aim: To determine the diagnostic efficacy of in-house developed synthetic peptide-based ELISA in viral infections of the CNS. Materials and Methods: A retrospective study was conducted in Central India Institute of Medical Science, Nagpur, Maharashtra, India. The suspected case of CNS viral infections of the patients were enrolled in this study from January 2013 to December 2015. Total 150 suspected cases of viral CNS infections and 135 control cases were recruited. Total 32 synthetic peptides of highly immunogenic proteins of respective seven neurotropic viruses were designed and synthesised. The designed peptides were evaluated in CSF samples of both the viral CNS infections and control cases for detection of Imunoglobulin G (IgG) and IgM antibodies using in-house developed antibody detection method. The developed tests were further compared with commercially available antibody detection ELISA kit. The sensitivity and specificity of peptide-ELISA were determined by Receiver Operating Curve (ROC) analysis and p-value was calculated by comparison of means by t-test. Results: Out of total 150 cases of CNS viral infections, a total of 31 CSF samples including 15 for CMV and 16 of JEV were positive by in-house peptide ELISA. The synthetic peptides STGDVVDISP, KQKSLVEL, RTLEVFKE, RSSNVED of CMV and ITYECPK, RRSVSVQT, GESSLVN of JEV showed a significant difference in mean absorbance value for IgM and IgG antibodies in CSF of suspected cases of viral CNS infection. Conclusion: The results demonstrated that the synthetic peptide-based ELISA is rapid, cost-effective, simple and efficient immunodiagnostic assay for initial screening of viral CNS infection.

Background: Circulating tumor cells (CTCs) are cells present in the blood stream that are antigenically or genetically similar to a specific tumor type and are markers of tumor diagnosis, prognosis, residual disease and metastasis. The ever-increasing burden of breast cancer globally warrants the incorporation of this all-inclusive marker in the diagnostic repertoire using the simplest of techniques. Aims: To identify CTCs in peripheral blood by cell block (CB) technique in cases of breast cancer diagnosed on fine-needle aspiration (FNA) or core needle biopsy (CNB) and to correlate their presence with nodal metastasis. Material and Methods: This study was conducted in the Department of Pathology, at a tertiary care hospital. Peripheral blood samples from a total of 30 cases of primary breast carcinoma diagnosed on FNA or CNB without prior neoadjuvant chemotherapy were analyzed using the CB technique. Results: The age ranged between 29-74 years with the most common presenting complaint being a palpable, single, unilateral breast lump. CTCs were detected in 2 (6.7%) cases with a

Brucellosis is an important zoonotic disease and has public health importance. In the present study, we studied the prevalence and associated risk factors of human brucellosis in the central Indian population from tertiary care health settings. A prospective observational study was conducted from March 2015 to February 2018 in patients attending the outpatient department (OPD) of Central India Institute of Medical Sciences (CIIMS), Nagpur. A total of 7026 individuals suspected of brucellosis were recruited based on prespecified inclusion criteria, additional risk factors, and clinical symptoms. Baseline, demographic and clinical characteristics were likewise recorded. Sera samples from recruited individuals were collected and subjected to anti-brucellosis antibody (IgM) detection using a commercial kit by ELISA assay. The overall seroprevalence of brucellosis reported from tertiary care health settings was 11% (772/7026). The majority of positive cases were from the states Madhya Pradesh (58.1%), followed by (Maharashtra (38.8%) and Chhattisgarh (2.9%). Adult age (20-60) and female groups were more vulnerable. Clinical symptoms like fever, arthralgia, and myalgia risk factors like animal exposure, consumption of raw milk, vegetable, and meat were significantly associated with brucellosis in the recruited population. Among the positive cases, high seroprevalence was associated with animal handlers (66.8%) compared to other occupationally exposed groups. The present study shows a high seroprevalence of brucellosis in health care settings. We emphasize regular screening of the disease in clinical settings to develop epidemiological data and initiate appropriate control measures.

Introduction: The diagnosis of Tuberculous Meningitis (TBM) has remained a challenge due to its insidious onset and the failure of conventional diagnostic tests. The present study aimed to identify the mycobacterial pathogen in the CSF of patients with TBM and a poor prognosis. Methods: We retrospectively recruited 224 TBM and 34 non-TBM patients admitted to the Central India Institute of Medical Sciences, Nagpur, India, in 2014. The CSF samples of these patients were subjected to a duplex PCR assay for the species-specific identification of the causative pathogen. Results: M. bovis and infection with M.tuberculosis were detected in 7% (18) and 32.9% (85) of the patients, respectively. Moreover, 14% (36) of the study samples were culture positive; however, the mycobacterial pathogens could not be differentiated to the species level. Conclusion: The present study findings emphasized the potentially vital importance of M. bovis identification for appropriate patient management. The obtained data also demonstrated the persistent significance of M. bovis, as a zoonotic pathogen.

Interventions to control the vectors of human diseases, notably malaria, leishmaniasis and dengue, have relied mainly on the action of chemical insecticides. However, concerns have been raised regarding the management of insecticides in vector-borne disease-endemic countries. Our study aimed to analyze how vector control insecticides are managed in selected countries to extract lessons learned. A qualitative analysis of the situation of vector control insecticides management was conducted in six countries. Multi-stakeholder meetings and key informer interviews were conducted on aspects covering the pesticide lifecycle. Findings were compared and synthesized to extract lessons learned. Centrally executed guidelines and standards on the management of insecticides offered direction and control in most malaria programs, but were largely lacking from decentralized dengue programs, where practices of procurement, application, safety, storage, and disposal were variable between districts. Decentralized programs were better at facilitating participation of stakeholders and local communities and securing financing from local budgets. However, little coordination existed between malaria, visceral leishmaniasis and dengue programs within countries. Entomological capacity was concentrated in malaria programs at central level, while dengue and visceral leishmaniasis programs were missing out on expertise. Monitoring systems for insecticide resistance in malaria vectors were rarely used for dengue or visceral leishmaniasis vectors. Strategies for insecticide resistance management, where present, did not extend across programs or sectors in most countries. Dengue programs in most countries continued to rely on space spraying which, considering the realities on the ground, call for revision of international guidelines. Vector control programs in the selected countries were confronted with critical shortcomings in the procurement, application, safety measures, storage, and disposal of vector control insecticides, with implications for the efficiency, effectiveness, and safety of vector control. Further international support is needed to assist countries in situation analysis, action planning and development of national guidelines on vector control insecticide management.

India has a higher tuberculosis (TB) burden than any other country, accounting for an estimated one-fourth of the global burden. Drug-resistant tuberculosis (DR-TB) presents a major public health problem in India. Patients with DR-TB often require profound changes in their drug regimens, which are invariably linked to poor treatment adherence and sub-optimal treatment outcomes compared to drug-sensitive TB. The challenge of addressing DR-TB is critical for India, as India contributes over 27% of global DR-TB cases. In recent decades, India has been proactive in its battle against TB, even implementing a revised National Strategic Plan to eliminate TB by 2025. However, to achieve this ambitious goal, the country will need to take a multifaceted approach with respect to its management of DR-TB. Despite concerted efforts made by the National TB Elimination Program, India faces substantial challenges with regard to DR-TB care, especially in peripheral and resource-limited endemic zones. This article describes some of the major challenges associated with mitigating the growing DR-TB epidemic in India and their implications.

BackgroundThis phase 1 clinical trial was conducted to determine the safety, maximum-tolerated dose (MTD), and pharmacokinetics of imatinib, bevacizumab, and metronomic cyclophosphamide in patients with advanced colorectal cancer (CRC).MethodsPatients with refractory stage IV CRC were treated with bevacizumab 5 mg kg(-1) i.v. every 2 weeks (fixed dose) plus oral cyclophosphamide q.d. and imatinib q.d. or b.i.d. in 28-day cycles with 3+3 dose escalation. Response was assessed every two cycles. Pharmacokinetics of imatinib and cyclophosphamide and circulating tumour, endothelial, and immune cell subsets were measured.ResultsThirty-five patients were enrolled. Maximum-tolerated doses were cyclophosphamide 50 mg q.d., imatinib 400 mg q.d., and bevacizumab 5 mg kg(-1) i.v. every 2 weeks. Dose-limiting toxicities (DLTs) included nausea/vomiting, neutropaenia, hyponatraemia, fistula, and haematuria. The DLT window required expansion to 42 days (1.5 cycles) to capture delayed toxicities. Imatinib exposure increased insignificantly after adding cyclophosphamide. Seven patients (20%) experienced stable disease for >6 months. Circulating tumour, endothelial, or immune cells were not associated with progression-free survival.ConclusionThe combination of metronomic cyclophosphamide, imatinib, and bevacizumab is safe and tolerable without significant drug interactions. A subset of patients experienced prolonged stable disease independent of dose level.

Abstract Introduction: Polymorphous low grade adenocarcinoma (PLGA) is a rare salivary gland neoplasm with an indolent course. It occurs primarily in the minor salivary glands but can rarely occur in the major salivary glands. It usually occurs in the fifth to seventh decades of life with female preponderance. Case Report: A 16-year-old male presented with recurrent painless swelling in the right preauricular region and with a history of surgical intervention at the same site in the past. His histopathology report was suggestive of pleomorphic adenoma. The swelling recurred after one year of excision and a superficial parotidectomy was performed. The detailed histopathological examination was suggestive of Polymorphous low grade adenocarcinoma. In view of close margins, the patient was given adjuvant radiotherapy. Thirty-three months post-surgery, he is alive and disease-free. We describe a rare case of PLGA of the parotid gland in a teenager with its clinical characteristics, histopathological features, and treatment. Conclusion: The occurrence of PLGA in the parotid gland is rare with only a few cases reported in literature. The diagnosis of PLGA is challenging due to morphological diversity.